MX2008008967A - Mucosal immunogenic substances comprising a polyinosinic acid - polycytidilic acid based adjuvant - Google Patents

Abstract

The present invention provides a polynucleotide adjuvant (PICKCa) composition and methods of use in eliciting an immune response, in particular a mucosal immune response. The polynucleotide adjuvant comprises of a polyriboinosinic-polyribocytidylic acid (PIC), at least one antibiotic and at least one positive ion. The present invention also provides an immunogenic composition comprising the polynucleotide adjuvant composition together with other immunogenic compositions such as an antigen (e.g., as in a vaccine). The present invention further contemplates methods of use of such adjuvant compositions, particularly in eliciting an immune response, in particular a mucosal immune response to an antigenic compound.

Description

MUCOSAL IMMONOGENIC SUBSTANCES THAT INCLUDE AN ADJUVANT BASED ON POLYINOSINIC ACID POLICITIDYLIC ACID FIELD OF THE INVENTION The invention relates, in general, to immunogenic compositions and methods for their use. More specifically, the invention relates to an immunogenic composition comprising an adjuvant polynucleotide in combination with one or more antigenic substances to be used to elicit a mucosal immune response, specific to the disease, in a host.

BACKGROUND OF THE INVENTION The immune system may exhibit specific immunity and non-specific immunity. The non-specific immunity comprises various cells and mechanisms, such as phagocytosis (the devouring of foreign particles or antigens) by macrophages or granulocytes, and the activity of natural killer cells (NK), among others. The non-specific immunity is based on less advanced mechanisms from the point of view of evolution, and does not exhibit the acquired nature of specificity and memory, which are exemplary signals of a specific immune response. The key differences between specific and non-specific immunity are based on the specificity of B and T cells. These cells predominantly acquire their response capacity after activation with a specific antigen and have mechanisms to exhibit memory in case of future exposure to that specific antigen. As a result, vaccination (which involves specificity and memory) is an effective protocol to protect against harmful pathogens. In general, B and T lymphocytes, which exhibit specific receptors on the surface of their cells for a given antigen, produce specific immunity. The specific immune system can respond to different antigens, in two ways: 1) humorally mediated immunity, which includes stimulation of the B cell and the production of antibodies or immunoglobulins, antigen and helper T cells (predominantly Th2); and 2) cell-mediated immunity, which usually involves T cells, including cytotoxic T lymphocytes (CTL), although other cells are also involved in the generation of a CTL response (e.g., cells displaying antigen and cells). Thl). The immune system has developed a different and specialized repertoire of immune responses to fight infections. The human immune system can be broadly subdivided into two interacting subsystems. The systemic immune system, comprising lymph nodes, bone marrow and spleen, which patrol internal organs and tissues, and the mucosal immune system, which comprises lymphoid tissues associated with mucosal surfaces and external secretory glands, which provides a defensive barrier against pathogens that enter the body through the epithelial lining of the respiratory, gastrointestinal, sensory and genitourinary tracts. The immunological responses of the systemic and mucosal immune systems have been developed with specific functions and remain largely different in their defensive mechanisms against pathogens. Mucosal immunity, for example, is generally characterized by the presence of a specialized class of antibodies, immunoglobulin A (IgA) antibodies, primarily secretory IgA (S-IgA) that protects mucosal surfaces. S-IgA antibodies neutralize pathogens in mucous membranes that have not yet crossed the mucosal barrier. In general, existing immunization strategies, involving intramuscular, subcutaneous, intraperitoneal or intradermal administration of antigens, evoke the systemic immune system in the production of different classes of antibodies, for example, immunoglobulin G (IgG) that neutralizes pathogens after they have entered the body. Vaccines administered by injection do not tend to evoke a substantial response of S-IgA. further, systemic immunity does not necessarily provide inhibition of the entry of pathogens to the body through the mucosal surfaces. Thus, a vaccination strategy that induces only a systemic immune response leaves the subject susceptible to infection through the mucosal surface, with the body's immune system fighting the pathogen until it is in circulation. Mucosal administration, on the other hand, induces mucosal responses (at local and sometimes remote administration sites) and systemic immune responses. Additionally, it is known that traditional methods of injected immunization regimens have numerous drawbacks, including the risk of infection and low tolerance by many individuals, with cases of induration (tissue hardening, hemorrhage (bleeding) and / or necrosis (local death). However, it is not possible to conclude that, since an adjuvant enhances a systemic immune response, it also necessarily intensifies a mucosal immune response.A typical example is aluminum hydroxide, which enhances immunogenicity systemic administration of a substance by intramuscular, subcutaneous, intraperitoneal, or intradermal administration, but which is ineffective in enhancing a mucosal immune response when administered by injection or by a mucosal route There has been an intense search, in recent years, for novel adjuvants, including those that intensify a r mucosal immune response. Efforts to take advantage of the protection of S-IgA in mucosal barriers have included oral immunization, as well as the application of monoclonal S-IgA antibodies directly to respiratory surfaces, in an effort to protect against the entry of pathogens. However, there continues to be a need for safe and effective adjuvants that are capable of eliciting a beneficial mucosal immune response in a host. The present invention provides novel immunogenic compositions, which exhibit improved safety and efficacy profiles, and methods for using said compositions, to enhance a mucosal immune response. Immunogenic compositions herein include an adjuvant polynucleotide and an antigen. LITERATURE The following references may be of interest: • JP'1093540A2; • US Patent No. 4,124,702, • US Patent No. 3,692,899, • US Patent No. 3,906,092, • US Patent No. 4,389,395, • US Patent No. 4,349,538, • US Patent No. 4,024,241, • US Patent No. 3,952,097; • Houston and coauthors, Infection and Immuniy, 14: 318-9, 1976C; • Wright and Adler-Moore, Biochemical and Biophysical Research Communications,; 131: 949-45, 1985; • Lin and co-authors, A new immunostimulatory complex (PICKCa) in experimental rabies: antiviral and adjuvant effects, Arch. Virol. , 131: 307-19, 1993. • Chinese Patent 93105862.7 • Gupta, R. K. and co-authors, Adj uvants - a balance between toxicity and adjuvantity, Vaccine, 11: 293-306, 1993; • Arnon, R. (Ed.) Synthetic Vaccines, 1: 83-92, CRC Press, Inc., Boca Raton, Fia., 1987. • Sela, M., Science, 166: 1365-1374 (1969); • U.S. Patent No. 6,008,200; • Ellouz and co-authors, Biochem & Biophys. Res. Comm. , 59: 1317, 1974; U.S. Patent No. 4,094,971, U.S. Patent No. 4,101,536 U.S. Patent No. 4,153,684 U.S. Patent No. 4,235,771 U.S. Patent No. 4,323,559, U.S. Patent No. 4,327,085, U.S. Patent No. 4,185,089, U.S. Patent No. 4,082,736, U.S. Patent No. 4,369,178 , U.S. Patent No. 4,314.99, U.S. Patent No. 4,082,735, U.S. Patent No. 4,186, 194; U.S. Patent No. 6,469,558 New Trends and Developments in Vaccines, edited by Voller et al., University Park Press, Baltimore, MD, E.

U. A., 1978; • Klein J. and co-authors, Immunology (2nd), Blackwell Science Inc., Boston (1997); • Gupa R. K. and Siber G. R., Adjuvants for human vaccines - current sta tus, problems and future prospecte, Vaccine, 13 (14): 1263-1276, 1995; • Richard T. Kenney and co-authors, Meeting Report - 2nd meeting on novel adjuvants currently in / close to human clinical testing, Vaccine 20, 2155-2163, 2002; • Labora tory techniques in Rabies, edited by F. X. Meslin, M. M. Kaplan, H. Koprowski, 4a, 1996, ISBN 92 4 1544 1 edition.

BRIEF DESCRIPTION OF THE INVENTION In general, the present invention relates to immunogenic compositions comprising a complex adjuvant of polyinosinic acid-polycytidylic acid, kanamycin and calcium, and methods for their use, to elicit a mucosal, specific immune response. Accordingly, a composition is provided comprising: (a) an adjuvant polynucleotide comprising: a polyriboinosinic-polyribocytidylic acid (PIC), at least one antibiotic and at least one positive ion; and (b) at least one antigen; wherein the composition is formulated for mucosal administration. In particular, the invention relates to the application of immunogenic compositions comprising a complex of polyinosinic acid-polycyclic acid, kanamycin and calcium, as an adjuvant that is safe for use in humans and non-human animals, and that when administered in combination with one or more antigenic and / or immunomodulatory substances, it intensifies the specific mucosal immunological response and, in certain applications, intensifies both a specific mucosal response and a specific systemic immune response. More particularly, the immunogenic composition according to the invention may comprise an adjuvant polynucleotide, heterogeneous molecules for molecular weight, wherein the molecular weight is at least 66,000 daltons.

BRIEF DESCRIPTION OF THE DRAWINGS Figure 1 illustrates the detection by ELISA of specific S-IgA titers in lung supernatant, after immunization with vaccines comprising PIKA and / or the whole, inactivated SARS antigen. Figure 2 illustrates the detection by ELISA of specific IgA titres in the blood serum, after immunization with vaccines comprising PIKA and / or whole SARS antigen, inactivated. Figure 3 illustrates the detection by ELISA of specific IgG titers in blood serum, after immunization with vaccines comprising PIKA and / or whole, inactivated SARS antigen. Figure 4 illustrates the detection by ELISA of specific S-IgA titers in lung supernatant, after immunization with vaccines comprising PIKA and / or the inactivated, divided influenza antigen. Figure 5 illustrates the detection by ELISA of specific S-IgA titers in intestine supernatant, after immunization with vaccines comprising PIKA and / or the inactivated, divided influenza antigen. Figure 6 illustrates the detection by ELISA of specific IgG titers in the blood serum, after immunization with vaccines comprising PIKA and / or the inactivated, divided influenza antigen. Figure 7 illustrates the detection by ELISA of specific IgA titres in the blood serum, after immunization with vaccines comprising PIKA and / or the inactivated, divided influenza antigen. Figure 8 illustrates the detection by ELISPOT of murine splenocytes that produce IL-2, after immunization with vaccines comprising PIKA and / or the inactivated, divided influenza antigen. Figure 9 illustrates ELISA detection of specific S-IgA in lung supernatant (dilution: 32x) after immunization with vaccines comprising PIKA or Al (OH) 3 and / or inactivated divided influenza antigen. Figure 10 illustrates detection by ELISA of specific S-IgA in intestine supernatant (dilution: 32x), after immunization with vaccines comprising PIKA or Al (OH) 3 and / or inactivated divided influenza antigen. Figure 11 illustrates the detection by ELISPOT of murine splenocytes that produce IFN-gamma, after immunization with vaccines comprising PIKA or alum and / or the divided, inactivated cold antigen. Figure 12 illustrates the detection by ELISPOT of murine splenocytes that produce IL-2, after immunization with vaccines comprising PIKA or alum and / or divided cold antigen, inactivated.

DETAILED DESCRIPTION OF EXEMPLARY MODALITIES OF THE INVENTION The present invention can be more easily understood by reference to the following detailed description of certain embodiments of the invention and the examples included therein. Throughout this application, when references are made to publications, the descriptions of those publications are incorporated herein in their entirety by reference, in order to describe in this application more fully the state of the art to which this present invention relates. 1 invention. Before the present invention is further described, it should be understood that this invention is not limited to the particular embodiments described, since, of course, they may vary. It should also be understood that the terminology used herein is for the purpose of describing the particular embodiments only, and is not intended to signify a limitation, since the scope of the present invention will be limited only by the claims that come at the end. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one having experience in the matter to which the present invention relates. While any method and any material similar or equivalent to those described herein can be used in practice, or can be tested for the present invention, preferred methods and materials will now be described. All publications mentioned herein are incorporated herein by reference, to describe and display the methods and / or materials in connection with which the publications are cited. It should be noted that, when used in the present and in the claims that come at the end, the singular forms "un", "una", "uno" and "el", "la", include referents in plural, a unless the context clearly requires otherwise. Thus, for example, the reference to "an immunogenic composition" includes a plurality of said compositions; and the reference to "antigen" includes reference to one or more antigens and their equivalents, known to those having experience in the art, and so on. It is further noted that the claims can be written to exclude any optional element. Thus, this signaling is intended to serve as a background for the use of exclusive terminology, such as "only", "only" and the like, in connection with the mention of the elements of the claim, or the use of a "negative" limitation.

DEFINITION OF TERMS Before giving the details of the present invention, it may be useful to understand it to establish the definitions for various terms that are used here. The term "adjuvant", when used herein, refers to any substance or mixture of substances that increases or diversifies the immune response of a host to an antigenic compound.

Specifically: 1. The term "PICKCa" generally refers to a composition of poly I: C, kanamycin and calcium, irrespective of the particular physical and immunogenic properties. 2. "Av-PICKCa" refers to a form of PICKCa used commercially as an antiviral drug. 3. "PIKA" refers to a composition of the invention comprising poly I: C, an antibiotic (e.g., kanamycin) and a positive ion (e.g., calcium); wherein PIKA is characterized by its physical characteristics (e.g., molecular weight, size and the like), such that, per administration, PIKA exhibits characteristics of an adjuvant with reduced adverse side effects (e.g., reduced toxicity) in relation, for example, with PICKCa, and higher potency (for example, it stimulates an increased immunological response) in relation, for example, to Av-PICKCa. The term "Poly I: C" or "PIC" refers to a composition comprising polyriboinosinic and polyribocytidylic nucleic acids, which can also be called polyinosinic acid-polycytidylic acid, respectively. "PIC-containing molecule" or "PIC-containing compound" refers, without limitation, to PIC, which may optionally be complexed or otherwise combined with at least one or both of an antibiotic (e.g., kanamycin) ) and a positive ion (eg, calcium), present in a composition comprising the PIC-containing molecule. In one embodiment, the PIC-containing molecule does not include poly-L-lysine, nor a derivative thereof in the complex. "Heterogeneous", when used herein, in the context of the adjuvant compositions of the invention, indicates that the components of the composition, e.g., molecules containing PIC, are not uniform with respect to a physical weight characteristic. molecular, size, or both. When a composition is described as heterogeneous for a given physical characteristic, and is further described by means of a scale of values for that physical characteristic, it is said that the composition will be composed substantially of molecules characterized by molecules having a physical characteristic that is distributed within and through the aforementioned scale. While the composition may not contain a molecule representative of each physical feature value within the upper and lower limits of a mentioned scale, the composition will generally include at least one molecule having the physical characteristic of the upper value and the lower value. The composition, in certain embodiments, may include molecules outside the designated scale of characteristics used to describe the composition. The molecules that are present in the composition, outside the prescribed scale, do not materially affect the basic and novel characteristics of the composition. The terms "mucosal" or "mucosal membrane" or "mucosal surface" refer to surfaces, passages and cavities that are in contact, directly or indirectly, with the external environment, including the surfaces of the respiratory, digestive systems , sensor and genitourinary. "Mucosal surface of the gastrointestinal tract" is intended to include the mucosa of the intestine (including the small intestine and the large intestine), the rectum, the lining of the stomach (gastric, oral cavity, and the like.) The term "formulated for mucosal administration" "refers to a composition that is adapted for administration to the mucosa (e.g., to a mucosal surface or a mucosal membrane) and which, therefore, is compatible with said administration." In some embodiments, the composition for mucosal administration is formulated by a different rectal, vaginal, nasal, oral or ophthalmic route (for example, the composition for administration to lung tissue is formulated, for example, by pulmonary administration.) The term "individual", used interchangeably herein with " "host", "subject" and "animal", includes humans and all domestic mammals, for example, livestock and pets and wild mammals, as well as birds, including, without limitation, horses, cows, pigs, sheep, goats, dogs, cats, rabbits, deer, mink, chickens, ducks, geese, turkeys, partridges and the like. The term "antibody" includes polyclonal and monoclonal antibodies, as well as the antigenic compound binding fragments of said antibodies, including the Fab, F (ab ') 2, Fd, Fv fragments, and the individual chain derivatives thereof. Also the term "antibody" includes antibodies that occur in nature, as well as antibodies that do not occur in nature, including, for example, chimeric, bifunctional and humanized antibodies, and related synthetic isoforms. The term "antibody" is used interchangeably with "immunoglobulin". When used herein, the term "antigenic compound" refers to any substance that can be recognized by the immune system (e.g., bound by means of an antibody or processed in order to elicit a cellular immune response) under appropriate conditions. An "antigen" refers to a substance, including compositions that are in the form of a vaccine, wherein the vaccine itself comprises an antigenic compound and may or may not comprise an adjuvant different from PIKA, than when administered by an appropriate route (eg, example, parenterally), induces a specific immune response, for example, the formation of antibodies, including antibodies that bind specifically to the antigen. Two of the characteristic aspects of the antigens are their immunogenicity, that is, their capacity to induce a specific immune response in vivo, and their antigenicity, that is, their ability to be selectively recognized by the antibodies whose origins are the antigens. An "antigen", when used herein, includes, but is not limited to, cells, cell extracts, proteins, lipoprotein, glycoproteins, nucleoproteins, polypeptides, peptides, polysaccharides, polysaccharide conjugates, peptide mimics of polysaccharides, lipids, glycolipids , carbohydrates, viruses, viral extracts, bacteria, bacterial extracts, fungi, fungal extracts, multicellular organisms, such as parasites, and allergens. The antigens may be exogenous (eg, from a source other than the individual to whom the antigen is administered, eg, from a different species) or endogenous (eg, originating from within the host, eg, an element). sick of the body, a cancer antigen, an antigen producing cell infected by virus, and the like). The antigens can be natural (for example, occurring in nature), synthetic or recombinant. Antigens include: crude extracts, whole cells and purified antigens; where "purified" indicates that the antigen is in a form that is enriched with respect to the environment in which the antigen normally occurs and / or in relation to the crude extract, for example, a cultured form of the antigen. An "immunogenic composition", when used herein, refers to a combination of two or more substances (e.g., an antigen and an adjuvant) that together elicit an immune response when administered to a host. The terms "polypeptide", "peptide", "oligopeptide" and "protein" are used interchangeably herein, and refer to a polymeric form of amino acids of any length, which may include encoded and uncoded amino acids, modified or derivatized amino acids chemically or biochemically, and polypeptides having modified peptide backbones. An "effective amount of an antigenic compound" refers to an amount of antigenic compound that, in optional combination with an adjuvant, will cause the subject to produce a specific immune response to the antigenic compound. The term "immune response" refers to any response to an antigenic or immunogenic compound, by the immune system of a vertebrate subject. Exemplary immunological responses include, but are not limited to: local and systemic cellular immunity, as well as humoral immunity, such as cytotoxic T lymphocyte (CTL) responses, including specific induction for CD8 + antigen, CTL, helper T cell responses , including responses of T cell proliferation and cytokine release, and B cell responses, including response to the antibody. The term "which elicits an immunological response", as used herein, generally comprises the induction and / or enhancement of an immune response. The term "that induces an immunological response" refers to an immune response that is stimulated, initiated or induced. The term "enhancing an immune response" refers to a pre-existing immune response, which is enhanced, amplified, supplemented, amplified, enhanced, increased or prolonged. The term "enhanced immune response" or similar means that the immune response is elevated, enhanced or enhanced to the benefit of the host, relative to the previous state of the immune response; for example, prior to the administration of an immunogenic composition of the invention. The terms "mucosal immune response" and "mucosal immunity" are terms that are well understood in the art, and refer to an immune response characterized, at least in part, by the production of secretory IgA and / or the stimulation of a mucosal CTL response in mucosal tissues, such as tissues of the gastrointestinal tract, including rectal tissues; vaginal tissues and tissues of the respiratory tract. The terms "humoral immunity" and "humoral immune response" refer to the form of immunity in which the antibody molecules are produced in response to the antigenic stimulus. The terms "cell-mediated immunity" and "Cell-mediated immune response" is intended to refer to the immune defense provided by lymphocytes, such as the defense provided by T-cell lymphocytes, when they enter intimate proximity with their victim cells. A cell-mediated immune response usually includes the proliferation of lymphocytes. When a "lymphocyte proliferation" is measured, the ability of the lymphocytes to proliferate is measured in response to a specific antigen. Lymphocyte proliferation refers to the proliferation of B cells, T-helper cells or cytotoxic T lymphocyte cells (CTL). The term "immunogenic amount" refers to an amount of antigenic compound sufficient to stimulate an immune response, when administered with an immunogenic composition to a subject, as compared to the immune response elicited by the antigen in the absence of the adjuvant polynucleotide. The term "immunopotentiating amount" refers to the amount of adjuvant necessary to effect an increase in antibody titer and / or cell-mediated immunity, when administered with an antigenic compound in a composition of the invention; in comparison with the increase in the level of immunity mediated by antibody and / or by cells, observed in the absence of the polynucleotide adjuvants. The terms "treatment", "treating", "treatment" and the like, are used herein to refer generally to obtaining a desired pharmacological and / or physiological effect. The effect can be prophylactic in terms of completely or partially preventing a disease or its symptoms, and / or it can be therapeutic, in terms of a stabilization or partial or complete cure for a disease and / or an adverse effect attributable to the disease . "Treatment", when used herein, covers any treatment of a disease in a subject, particularly a mammalian subject, more particularly a human, and includes: (a) preventing the disease or its symptoms from occurring in an individual who could be predisposed to the disease or symptom, but who has not yet been diagnosed as having them; (b) inhibiting the symptom of the disease, for example, by stopping its development, or alleviating the symptom of the disease, i.e., causing the regression of the disease or symptom; (c) reducing a level of an effect produced by the infectious agent of a disease (eg, a toxin, an antigen and the like); and (d) reducing an undesirable physiological response to the infectious agent of a disease (e.g., fever, tissue edema and the like). When used herein, the term "mixing" includes any method for combining the components of the composition; said methods include, but are not limited to: stirring, dispensing, dissolving, emulsifying, coagulating, suspending or otherwise physically combining the components of the composition. A "pharmaceutically acceptable salt" of a compound means a salt that is acceptable for use in a pharmacy, and that possesses the pharmacological activity of the parent compound. Said salts include: (1) the acid addition salts, formed with inorganic acids, such as: hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid and the like; or formed with organic acids, such as: acetic acid, propionic acid, hexanoic acid, cyclopentanepropionic acid, glycolic acid, pyruvic acid, lactic acid, malonic acid, succinic acid, malic acid, maleic acid, fumaric acid, tartaric acid, citric acid , benzoic acid, 3- (4-hydroxybenzoyl) benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, 1,2-ethanedisulfonic acid, 2-hydroxyethanesulfonic acid, benzenesulfonic acid, 4-chlorobenzenesulfonic acid, 2-naphthalenesulfonic acid , 4-toluenesulfonic acid, camphorsulfonic acid, glucoheptonic acid, 4,4'-methylenebis (3-hydroxy-2-ene-l-carboxylic acid), 3-phenylpropionic acid, trimethylacetic acid, terbutylacetic acid, lauryl sulfuric acid, gluconic acid, glutamic acid, hydroxynaphthoic acid, salicylic acid, stearic acid, muconic acid and the like; or (2) salts formed when an acidic proton present in the original compound is replaced by a metal ion, for example, an alkali metal ion, an alkaline earth metal ion or an aluminum ion; or is coordinated with an organic base, such as ethanolamine, diethanolamine, triethanolamine, tromethamine, N-methylglucamine, and the like. The term "unit dose form", when used herein, refers to physically discrete units, suitable as unit doses for human and animal subjects; each unit containing a predetermined amount of compounds of the present invention, calculated in an amount sufficient to produce the desired effect, in association with a diluent, carrier or vehicle acceptable for pharmaceutically / physiologically acceptable use.

EXEMPLARY MODALITIES OF THE INVENTION The present invention is directed to immunogenic compositions and methods useful for the induction and / or enhancement of an immunological response, which can be mucosal and / or systemic, humoral and / or cell-mediated, in a human, in a non-human animal or in a cell culture.

In general, an immunogenic composition according to the invention comprises an antigen (an "antigenic composition") and an adjuvant. The presence of the adjuvant enhances or modifies the immune response to the antigen.

The adjuvant can alter the quality of the immune response by affecting the subclasses (isotypes) of immunoglobulins, chemokines and / or cytokines produced. As a result, responses of innate, humoral and / or cell-mediated immunity are most effective with the presence of the adjuvant. A particular advantage is the effectiveness of the PIKA adjuvant in combination with an antigenic substance, to induce a specific humoral immune response, thereby enhancing protective immunity. A further important advantage is that the PIKA adjuvant, in combination with an antigen, can induce a specific, cell-mediated immune response, which is essential for a therapeutic vaccine, to limit and treat viral, bacterial and parasitic intracellular infections. Accordingly, compositions having the unique product attributes that make them most suitable for use as vaccines to be administered to animals and / or humans, which face the need for a safe adjuvant that elicits a beneficial immune response are included in the invention. Accordingly, the present invention provides immunogenic adjuvant compositions that can be used safely in humans and animals. Accordingly, there is provided an immunogenic composition comprising: (a) an adjuvant polynucleotide comprising: a polyriboinosinic acid-polyribocytidylic acid (PIC); at least one antibiotic and at least one positive ion; and (b) at least one antigen; wherein the composition for mucosal administration is formulated. In particular, the immunogenic composition according to the invention may comprise an adjuvant polynucleotide composition with heterogeneous molecules to influence molecular weight; where the molecular weight is at least 66,000 dalton. The value of 66,000 dalton corresponds to the size of about 6.4 svedberg. Consequently, a molecular weight scale of 66,000 dalton to 1,200,000 dalton corresponds to a size of about 6.4 to 24.0 svedberg. More specifically, the present invention provides the PIKA adjuvant composition comprising a polynucleotide, an antibiotic and a positive ion; wherein the polynucleotide can be polyriboinosinic-polyribocytidylic acid (PIC); the antibiotic can be kanamycin and the ion can be calcium. In an aspect of particular interest, the invention provides an immunogenic composition for enhancing the antigenicity of an antigenic compound, comprising the adjuvant polynucleotide composition, which is capable of eliciting a cell-mediated, antigen-specific immune response. In an aspect of particular interest, the invention provides an immunogenic composition for enhancing the antigenicity of an antigenic compound comprising the adjuvant polynucleotide composition, which is capable of eliciting a humoral immune response specific for the antigen. In an aspect of particular interest, the invention provides an immunogenic composition for enhancing the antigenicity of an antigenic compound, comprising the adjuvant polynucleotide composition that is capable of eliciting a specific, cell-mediated and humoral combined immune response. In an aspect of particular interest, the invention provides an adjuvant composition or an immunogenic composition comprising an adjuvant composition, wherein the adjuvant composition or the immunogenic composition is freeze-dried. In an aspect of particular interest, the invention provides the use of an adjuvant polynucleotide composition for the preparation of a medicament for enhancing the immunogenic response of a host.

The adjuvant polynucleotide An immunogenic composition herein comprises an adjuvant polynucleotide containing PIC, for example, a PIKA composition, and is generally composed of polyinosinic acid, polycytidyl acid, an antibiotic (e.g., kanamycin) and a divalent cation (eg, example, calcium). It will be understood that the reference to PIKA herein is exemplary of such adjuvants containing PIC. Adjuvants containing PIC, which are of interest, can be manufactured using methods that can be obtained in the art. The adjuvant composition containing PIC can be manufactured through any appropriate process. For example, the adjuvant polynucleotide composition can be made by mixing polyinosinic acid, polycytidyl acid, an antibiotic and the positive ion source, in a sodium chloride / phosphate buffer, which has a pH between pH 6 and pH 8. Polyinosinic acid and polycytidylic acid are usually provided at concentrations of 0.1 to 10 mg / mL, usually 0.5 to 5 mg / mL and, more usually, 0.5 to 2.5 mg / mL. The hyperchromicity value must be greater than 10 percent; greater than 15 percent, greater than 20 percent or greater than 50 percent. The preparation of the PIC and the combination with the antibiotic (for example, kanamycin) and the positive ion (for example, calcium), is generally carried out under quality standards consistent with the Good Manufacturing Process international standard. In certain embodiments of the present invention, the antibiotic component of the adjuvant is kanamycin. When the antibiotic is kanamycin, in some embodiments, the kanamycin that is present in the adjuvant polynucleotide composition is used together with, or is substituted by, one or more antibiotics selected from the group including: tobramycin, anthracyclines, butyrosine sulfate, gentamicins, hygromycin, amikacin, dibecacin, nebramycin, metrzamide, neomycin, puromycin, streptomycin and streptozocin. The antibiotic (e.g., kanamycin or the like) which is in the adjuvant polynucleotide composition of the present invention, is generally provided at a concentration of about 10 units / mL to 100,000 units / mL; from about 100 units / mL to 10,000 units / mL; or from about 500 units / mL to 5,000 units / mL. In some embodiments of the present invention, the adjuvant polynucleotide composition additionally comprises a positive ion (cation), usually a divalent cation, typically an alkali metal cation. The positive ion is generally provided in the composition of the invention as a source of positive ions, such as a salt or a complex, for example, an organic or inorganic salt or an organic or inorganic complex, usually as an inorganic salt or a complex organic. Exemplary positive ions include, but are not necessarily limited to: calcium, cadmium, lithium, magnesium, cerium, cesium, chromium, cobalt, deuterium, gallium, iodine, iron or zinc. The positive ion can be provided in the form of any suitable organic salt or complex, including, but not necessarily limited to, the chloride, fluoride, hydroxide, phosphate or sulfate salts. For example, when the positive ion is calcium, the ion may have the form of calcium carbonate, calcium chloride, calcium fluoride, calcium hydroxide, calcium phosphates or calcium sulfate. The positive ion (eg, calcium) can be provided in the composition of the invention at a concentration in the scale of about 10 umoles to 10 mmol / mL, usually from about 50 umoles to 5 mmol / mL and, more usually , from around 100 umoles to 1 mmol / mL. The term "umol" is used throughout this document to refer to micromoles. When the positive ion present in the adjuvant composition of the invention is calcium, it can be in combination with, or replaced by, other positive ions, including: cadmium, lithium, magnesium, cerium, cesium, chromium, cobalt, deuterium, gallium, iodine , iron and zinc; wherein the ions may take the form of inorganic salts or organic complexes. The resulting composition is an adjuvant containing PIC, which additionally contains an antibiotic and a positive ion. In a particular embodiment, when the antibiotic is kanamycin and the ion is calcium, the product can be described as PICKCa. In a related embodiment, the PICKCa composition may contain unrestricted molecules of different physical characteristics.

The adjuvant PIKA composition In some exemplary, particular embodiments, the adjuvant polynucleotide is PIKA. PIKA can be produced in a variety of ways, the production of PICKCa being of particular interest. PIKA can be produced from PICKCa, by means of additional manufacturing processes, which involve the isolation and / or concentration of molecules of a defined molecular size and / or weight. The separation and concentration of polynucleotide molecules are carried out, with particular characteristics, using filtration, chromatography, • heat treatment, centrifugal separation, electrophoresis and similar methods that are common and current procedures and are known to those having experience in the art. . The immunogenic composition can be prepared as a dry powder, a liquid solution, suspension or emulsion. The preparation of formulations of a desired immunogenic composition is generally described in Vaccine, 4a. edition, by Stanley A. Plotkin and co-authors, W. B. Saunders Company, 4th. edition, 2003. Suitable formulations are also described, for example, in A. Gennaro (2000) Remington: The Science and Practice of Pharmacy, 20a. edition, Lippincott Williams and Wilkins; Pharmaceutical Dosage Forms and Drug Delivery Systems (1999), H. C. Ansel et al., Eds., 7a. edition, Lippincott, Williams and Wilkins; and Handbook of Pharmaceutical Excipient (2000), A. H. Kibbe et al., eds., 3a. edition, Amer. Pharmaceutical Assoc; Methods in Molecular Medicine, volume 87: Vaccine Protocols, 2a. edition (2003), Humana Press; Mucosal Vaccines (1996), Kiyomo et al., Eds., Academic Press; and Vaccine Adjuvants: Preparation Methods and Research Protocols (2000) D. T. O'Hagan, Humana Press. In the modalities of particular interest, the invention contemplates an adjuvant which is generally referred to as PIKA, which comprises a polyriboinosinic-polyribocytidylic acid (PIC); an antibiotic (for example, kanamycin), and a positively charged ion (for example, a calcium ion); wherein the composition contains molecules of the adjuvant heterogeneous for molecular weight, which have a molecular weight of about 66,000 to 1,200,000 Daltons. That is, the adjuvant composition comprises molecules that have a weight distribution on the scale of about 66,000 to 1,200,000 dalton. In the related embodiments, the molecules of the PIKA composition, the adjuvant polynucleotide, present in the composition are heterogeneous; that is, the weight of the adjuvant molecules is distributed within a scale of molecular weight in which the molecular weight is from about 300,000 to 1,200,000 dalton, or from about 66,000 to 660,000 dalton, or from about 300,000 to 660,000 dalton or about 300,000 to 2,000,000 dalton, or about 66,000 dalton to about 100,000 dalton, from 100,000 to 200,000 dalton, from about 300,000 dalton to about 4,000,000 dalton, or from about 500,000 dalton to 1,000,000 dalton, or from around 1,000,000 dalton to 1,500,000 dalton, or from around 1,500,000 dalton to 2,000,000 dalton, or from around 2,000,000 dalton to 2,500,000 dalton, or from around 2,500,000 dalton to 3,000,000 dalton, or from around 3,000,000 dalton to 3,500,000 dalton, or from around 3,500,000 dalton to 4,000,000 daltons, or from around 4,000,000 daltons to 4,500,000 daltons, or from around 4,500,000 daltons to 5,000,000 daltons. In related embodiments, the molecules of the PIKA composition, the adjuvant polynucleotide, present in the composition, have an average molecular weight equal to or greater than 66,000 dalton, greater than 150,000 dalton, or equal to or greater than 250,000 dalton, or equal to or greater that 350,000 daltons, or equal to or greater than 500,000 daltons, or equal to or greater than 650,000 daltons, or equal to or greater than 750,000 daltons, or equal to or greater than 1,000,000 daltons, or equal to or greater than 1,200,000 daltons, or equal to or greater than 1,500,000 Dalton, or equal to or greater than 2,000,000 dalton. In embodiments of particular interest, the invention incorporates an adjuvant, which is generally referred to as PIKA, which comprises a polyriboinosin-polyribocytidylic acid (PIC), an antibiotic and a positive ion; wherein the composition contains heterogeneous adjuvant molecules; that is, the size of the adjuvant molecules is distributed within a scale of molecular sizes, for a molecular size that has a sediment coefficient of Svedbergs (S) of around 6.43 S at 24.03 S. In related modalities, the molecules of the composition of PIKA, the adjuvant polynucleotide, present in the composition, are heterogeneous; that is, the size of the adjuvant molecules is distributed within a scale of molecular sizes, in which the molecular size is from about 12.8 S to 24.03 S, or from about 3 S to 12 S, or around 6.43 to 18.31 S, or from around 12.8 to 18.31 S, or from around 12.8 S to 30.31 S, or from around 12.8 S to 41.54 S, or from around 13.5 S to 18.31 S, or around 13.5 S at 24.03 S, or from around 16.14 to 22.12 S, or from around 22.12 S to 26.6 S, or from around 26.6S to 30.31 S, or from around 30.31 S to 33.55 S, or from around 33.55 S to 36.45 S, or from around 36.45 S to 39.1 S, or from around 39.1 S to 41.54 S, or from around 41.54 S or 43.83 S, or from around 43.83 S to 45.95 S.

In other related embodiments, the composition of PIKA, the adjuvant polynucleotide, has an average sedimentation coefficient (in svedberg) of more than 9, or more than 12, or more than 13.5 or more than 15, or more than 16, or more of 17, or more than 18, or more than 19, or more than 20, or more than 21, or more than 22, or more than 25, or more than 30.

Immunogenic properties An immunogenic composition, including PIKA and an antigen, can generally induce a specific immune response to the antigen in at least two ways: i) humoral mediated immunity, which includes stimulation of B cells and the production of antibodies or immunoglobulins (other cells are also involved in the generation of an antibody response, for example, cells that present antigen, including macrophages and helper T cells (Thl and Th2), and ii) cell-mediated immunity, which generally involves cell T, including cytotoxic T lymphocytes, although other cells are also involved in the generation of a cytotoxic response of T lymphocytes (e.g., Thl and / or Th2 cells and cells that present antigen). Additionally, the adjuvant polynucleotide composition can alter the quality of the immune response, affecting the subclasses (isotypes) of immunoglobulins produced, as well as their affinities. The degree and nature of the immunogenic response induced by an immunogenic composition of the present can be determined in that way, by measuring the presence of molecules, including cytokines, chemokines and antibodies produced by cells of the immune system. The invention herein provides immunogenic substances comprising the PIKA adjuvant which enhances the overall level of immune response in a host, inducing a mucosal immune response. In certain embodiments, an immunogenic composition herein induces a mucosal immune response and enhances the systemic level of immunity. The induction of a mucosal immune response, as well as the intensification of systemic immunity are of interest to treat infectious diseases caused by pathogenic organisms that enter the body through the mucosal surface. The examples provided demonstrate that an immunogenic composition comprising PIKA and a SARS antigen, when administered by peritoneal injection, induces a systemic immune response, in which the expression of specific IgA and specific IgG in the blood, are measures of activity immunological system. However, an identical immunogenic composition, comprising PIKA and a SARS antigen, when administered by peritoneal injection, did not induce a mucosal immune response, wherein the expression of S-IgA is a measure of mucosal immunological activity. Surprisingly, the identical immunogenic composition, comprising PIKA and a SARS antigen, when administered mucosally, induces a mucosal immune response, as indicated by the expression of specific S-IgA on the mucosal surface. Example 1 illustrates that the presence of the PIKA adjuvant in an immunogenic composition, administered by peritoneal injection, does not induce an enhanced expression of specific S-IgA in the mucosal membrane. However, the presence of the PIKA adjuvant in an immunogenic composition administered mucosally, induces the expression of specific S-IgA in the mucosal membrane, in a dose-dependent manner (Table A). The presence of the PIKA adjuvant in an immunogenic composition, administered by peritoneal injection, caused an increase, dependent on the dose, in the presence of IgA in the blood. Additionally, the presence of the PIKA adjuvant in the mucosally administered immunogenic composition also increased the level of specific IgA in the blood, in a way that depends on the dose (Table B). In addition, the presence of the PIKA adjuvant in an immunogenic composition administered by peritoneal injection, caused an increase, dependent on the dose, in the presence of IgG in the blood. The presence of the PIKA adjuvant in the mucosally administered immunogenic composition also increased the level of specific IgG in the blood, in a manner dependent on the dose (Table C). The results of these examples are summarized in Figures 1 to 3. The production of specific IgG in the blood, induced by the mucosal supply of the PIKA vaccine composition and the SARS antigen, was more than 70 percent of the levels observed for peritoneal delivery (Table B). Thus, the presence of PIKA in an immunogenic substance delivered mucosally has the unexpected additional benefit of inducing an immune response in both mucosal and systemic immunological subsystems. Example 2 demonstrates that the presence of PIKA induces a mucosal as well as a systemic immune response. In addition, it was unexpectedly observed that mucosal administration of an immunogenic composition comprising PIKA induced a mucosal immune response at a remote mucosal site. Additionally, it was unexpectedly observed that mucosal administration of a composition comprising PIKA induced a T-cell mediated immune response. In Example 2, the influenza antigen used was a vaccine against human influenza VAXIGRIP approved by Sanofi Pasteur, which comprises strains H1N1, H3N2 and similar strains, and strain b / Shanghai5 / 361/2002. Influenza antigen alone, and a composition comprising the influenza antigen plus PIKA, administered by subcutaneous injection, induces a specific, systemic, humoral and immune systemic response; but only a weak specific mucosal immune response, when measured by the production of S-IgA on the mucosal surfaces of the lungs and intestines. The administration of the influenza antigen alone and the influenza antigen combined with alum (a recognized vaccine antigen), by means of nasal drops, also induced only a weak specific mucosal immune response (see tables E and F, figures 4 and 5). , when measured by the production of S-IgA in the mucosal surfaces of lungs and intestines. 4 In contrast, the presence of PIKA in an immunogenic composition comprising the influenza antigen, induced an unexpectedly strong specific mucosal site on the mucosal surface of the lung, when measured by the production of S-IgA (Table E, Figure 4 ). It was further observed that, in the remote mucosal site of the intestine there was also a strong, specific mucosal immune response, as indicated by the presence of S-IgA (Table F, Figure 5). Furthermore, the administration of an immunogenic composition comprising PIKA and the influenza antigen, induced a strong specific systemic response, both humoral when measured by specific IgA and specific IgG in the blood serum (see tables G and H, figures 6). and 7), as well as an immune response mediated by T cells, and measured by the production of 11-2 by splenocytes (table I, figure 8). Example 3 further demonstrates that the presence of PIKA enhances the mucosal immune response, while specifically amplifying the cell-mediated immune response. In comparison, the use of an alum adjuvant, under identical experimental conditions, did not enhance the degree of mucosal immunological activity, nor the cell-mediated immune response.

Additional Aspects In another embodiment, an immunogenic composition herein is further defined by the relative presence of the PIKA adjuvant and the antigen or antigens; where the presence is measured in terms of one or more characteristics of quantity, concentration, volume, number of molecules or other recognized metric. In related embodiments, an immunogenic composition of the present invention comprises an adjuvant polynucleotide composition and an antigen or several antigens, wherein the presence of the adjuvant and the antigens, in terms of weight or number of molecules, is in a ratio of from 1 to 1000, from less than 1 to 900, from less than 1 to 800, from less than 1 to 700, from less than 1 to 500, from less than 1 to 400, from less than 1 to 300, from less than 1 a 200, from less than 1 to 100, from less than 1 to 50, from less than 1 to 10, from less than 1 to 5, from less than 1 to 2, from around 1 to 1, from more than 2 to 1 , of more than 5 to 1, of more than 10 to 1, of more than 50 to 1, of more than 100 to 1, of more than 200 to 1, of more than 300 to 1, of more than 400 to 1, of more than 500 to 1, of more than 600 to 1, of more than 700 to 1, of more than 800 to 1, of more than 900 to 1, of more than 1,000 a 1. In a further related embodiment, an immunogenic composition herein is defined in terms of dose, which is the amount of vaccine that must be administered to induce the optimal beneficial immune response or, alternatively, the dose scale that can be administer, from the minimum required to elicit an immune response, up to the maximum dose, beyond which the incremental beneficial response is not medically justified, in the context of the potential induction of adverse side effects. In certain embodiments of particular interest, the immunogenic composition comprises the adjuvant polynucleotide composition and the antigen; wherein the presence of the antigen in a unit dose is provided in an amount that is greater than 0.1 ug, is greater than 0.5 ug, is greater than 0.01 mg, is greater than 0.005 mg, is greater than 0.01 mg, is greater than 0.025 mg, is greater than 0.05 mg, is greater than 0.075 mg, is 0.1 mg, is greater than 0.25 mg, is greater than 0.5 mg, is greater than 1.2 mg, is greater than 1.4 mg, is greater than 1.6 mg, is greater than 1.8 mg, is greater than 2.0 mg, is greater than 2.5 mg, is greater than 3 mg, is greater than 3.5 mg, is greater than 4 mg, is greater than 5 mg, is greater than 6 mg, is greater than 7 mg, is greater than 8 mg, is greater than 9 mg, is greater than 10 mg, is greater than 15 mg, is greater than 20 mg, is greater than 25 mg, or is greater than 50 mg. An optimal amount of antigen can be determined, and the optimal ratio of antigen to PIKA adjuvant can be determined by means of common studies that involve observations of antibody titers and other immunogenic responses in the host.

Antigens In one embodiment of particular interest, the invention provides an adjuvant polynucleotide composition, together with an antigen or a vaccine, wherein the source of the antigen is a human antigen, an animal antigen, a plant antigen, one or more agents of infectious agents of any virus, bacteria, including mycobacteria, fungi or parasites, cancer antigen, allergenic agents and other antigens, such as to develop autoimmune diseases.

In certain embodiments, the antigens may be derived from a natural source, either raw or purified, and may be used in their original live form, or after they have been killed or inactivated, or truncated, or attenuated, or transformed into a form not reversible, or detoxified, or mutated to a non-toxic form, or filtered or purified. In some embodiments, the antigen is an isolated microorganism antigen, for example, a viral antigen, a bacterial antigen, a fungal antigen, an allergy antigen, a cancer antigen or an autoimmune antigen. In other embodiments, the antigen is a whole antigen, inactivated. Methods for inactivating a whole antigen are well known in the art; any known method for inactivating an antigen can be used, and can be selected appropriately for the type of antigen of interest. Those methods for inactivating an antigen include, for example, the use of photoreactive compounds, oxidizing agents, irradiation (e.g., UV irradiation, gamma irradiation); combinations of riboflavin and UV irradiation; solvent-detergent treatment (for example, treatment with the organic solvent tri-N-butyl phosphate, with a detergent such as Tween 80); treatment with polyethylene glycol, pasteurization (heat treatment), and treatment at low pH; moderate enzymatic treatment with pepsin or trypsin; phototreatment with methylene blue (MB); treatment with dimethylmethylene blue (DMMB) and visible light; treatment with S-59, a psoralen derivative and UVA illumination; and similar. In a particularly interesting, related embodiment, the antigen can be synthesized by means of solid phase synthesis, or it can be obtained by recombinant genetics, or it can be artificially manufactured otherwise, so as to mimic the immunogenic properties of a pathogen . The antigen can be acellular, capsular, infectious clone, replicon, vectorized, microencapsulated, monovalent, bivalent or multivalent. In some embodiments, an immunogenic composition of the present invention comprises an adjuvant polynucleotide and at least two different antigens; for example, in some embodiments, an immunogenic composition of the present invention comprises two antigens, three antigens, four antigens, five antigens or more than five antigens. Antigen polypeptides can be isolated from natural sources, using common and current methods for protein purification, known in the art, including, but not limited to: liquid chromatography (e.g., high performance liquid chromatography, chromatography in fast protein liquid, etc.); size exclusion chromatography, gel electrophoresis (including one-dimensional gel electrophoresis, two-dimensional gel electrophoresis), affinity chromatography or other purification technique. Peptide synthesis techniques in solid phase can be employed, in which said techniques are known to those having experience in the material. See Jones, The Chemical Synthesi s of Peptides (Clarendon Press, Oxford) (1994). Generally, in such methods a peptide is produced through the sequential addition of activated monomer units, to a growing peptide chain, solid phase bound. Recombinant DNA techniques, well established, can be used for the production of polypeptides; Such methods include, but without limitation to them, for example, an expression construct comprising a nucleotide sequence encoding a polypeptide is introduced into an appropriate host cell (e.g., a eukaryotic host cell, grown in a single cell entity, in a culture). cell in vi tro, for example, a yeast cell, an insect cell, a mammalian cell, etc.), or a prokaryotic cell (for example, developed in a cell culture in vi tro), which generates a genetically modified host cell; under appropriate culture conditions, the protein is produced by the genetically modified host cell. In some embodiments, the antigen is a purified antigen, for example, with a purity of about 25 percent to 50 percent; with a purity of about 50 percent to around 75 percent; with a purity of about 75 percent to around 85 percent; with a purity of about 85 percent to around 90 percent; with a purity of about 90 percent to about 95 percent; with a purity of about 95 percent to about 98 percent; with a purity of about 98 percent to about 99 percent, or with a purity of over 99 percent. The antigen can be acellular, capsular, infectious clone, replicon, vectorized, microencapsulated, monovalent, bivalent or multivalent. The adjuvant polynucleotide composition of the present invention can also be used to enhance the immune response against antigens produced through the use of DNA vaccines and / or proteins expressed in DNA. The DNA sequences in these vaccines encoding the antigen may be "naked" or may be contained in a delivery system, such as in liposomes. In an aspect of particular interest, an immunogenic composition can be defined herein by means of the selection of the antigen or antigens that are used in combination with the PIKA adjuvant. In one embodiment of particular interest, the present invention provides an adjuvant polynucleotide composition and method of use, wherein the adjuvant polynucleotide composition comprises the PIKA adjuvant together with an antigen, wherein exemplary antigens include, but are not limited to, they, the antigens that are of pathogens of infectious disease, that enter the host through a mucosal surface, as described in table N. Consequently, table N describes organisms that can serve as a source of antigens, and diseases that can be the result of infection of the mucosal membrane.

TABLE N In a particular embodiment, the present invention provides an adjuvant polynucleotide composition and method of use, wherein the adjuvant polynucleotide composition comprises the PIKA adjuvant together with an allergy antigen that enters the host through a mucosal surface.; wherein the antigen is of human origin or a source of animal allergy, including: vegetables, animals, fungi, insect food, dust and mites and the like. Allergens include, but are not limited to: environmental aeroallergens; plant pollens, such as ragweed / hay fever, grass pollen allergens; grass pollen allergens, Johnson grass, tree pollen allergens, Italian grass, arachnid allergens, such as house dust mite allergens (e.g., Der p I, Der F I, etc.); storage mite allergens; Japanese cedar pollen / hay fever; mold spore allergens; animal allergens (eg, dog allergens, guinea pigs, hamsters, gerbils, rats, mice, etc.); food allergens (eg crustacean allergens, nuts, such as peanuts, citrus fruits); insect allergens, poisons (of hymenoptera, of jicote, of honey bee, of wasp, of hornet, of ant arriera); allergens from other environmental insects, from cockroaches, flies, mosquitoes, etc .; bacterial allergens, such as streptococcal antigens, parasite allergens, such as Ascaris antigen, viral antigens, fungal spores, drug allergens, antibiotics, penicillins and related compounds; other antibiotics, whole proteins, such as hormones (insulin), enzymes (streptokinase), all drugs and their metabolites, capable of acting as incomplete antigens or haptens; industrial chemical substances and their metabolites, capable of acting as haptens and functioning as allergens (for example, acid anhydrides (such as trimellitic anhydride) and isocyanates (such as toluene diisocyanate)); occupational allergens, such as flour (for example, the allergens that cause the baker's asthma), castor bean, coffee bean, and industrial chemicals described above; fly allergens and human proteins in non-human animals. Allergens include, but are not limited to: cells, cell extracts, proteins, polypeptides, peptides, polysaccharides, polysaccharide conjugates, peptides and nonpeptide mimics of polysaccharides and other molecules, small molecules, lipids, glycolipids and carbohydrates. Examples of natural allergens, of animals and plants, include, but are not limited to, specific proteins of the following genera: Canids (Canis familiaris), Dermatophagoides (eg, Dermatofagoides farinae); Felids (Felis domesticus); Ambrosia ('Ambrosia artemisifolia); Lolium (for example, Lolium perenne or Lolium multiflorum), Crytomeria (Cryptomeria japonica); Alternate (Alternaria alternata); Alder, Alnus (Alnus gultinoasa), Betula (Betula verrucosa), Quercus (Quercus alba), Olea (Olea europa); Artemisia (Artemisia vulgaris), Plantago (for example, Plantago lanceolata); Parietaria (for example, parietaria officinalis or Parietaria judaica); Blattella (for example, Blattella germanica); Apis (for example, Apis multiflorum); Cupressus (for example, Cupresus sempervirens, Cupressus arizonica and Cupressus macrocarpa); Juniperus (for example, Juniperus sabinoides, Juniperus virginiana, Juniperus communis and Juniperus ashei); Thuya (for example, Thuya orientalis), Chamaecyparis (for example, Chamaecypaaris obtusa); Periplaneta (for example, Periplaneta americana), Agropyron (for example, Agropyron repens, Sécale (for example, Sécale cereale), Triticum (for example, Triticum aestivum), Dactylis (for example, Dactylis glomerata), Festuca (for example, Festuca elatior), Poa (for example, Poapratensis or Poa compressa); Oats, for example, Avena sativa; Holcus (for example, Holcus lanatus), Anthoxanthum (for example, Anthoxanthum odoratum), Arrhenatherum (for example, Arrhenatherum elatius), Agrostis (for example, Agrostis alba); Phleum (for example, Phleum pratense), Phalaris (for example, Phalaris arundinacea), Paspalum (for example, Paspalum notatum); Sorghum (for example, Sorghum halepensis); and Bromus (for example, Bromus inermis). In one embodiment of particular interest, the present invention provides an adjuvant nucleotide composition and a method of use, wherein the adjuvant polynucleotide composition comprises the PIKA adjuvant together with an autoimmune antigen that enters the host through a surface mucosal In some embodiments, an immunogenic composition of the present invention comprises, in addition to a PIKA adjuvant and an antigen, one or more additional agents, for example, immunomodulatory agents, carriers and the like. In a particular mode of interest, the present invention provides an immunogenic composition and method for its use; wherein the immunogenic composition comprises the PIKA adjuvant, an antigen or a vaccine, together with another immunomodulatory substance, including adjuvants; wherein suitable immunomodulatory substances include, but are not limited to: an aluminum composition, such as aluminum hydroxide; oil-in-water emulsion compositions, or emulsions comprising an immunogenic substance, including Freund's complete adjuvant, an oil-in-water emulsion containing heat killed, dried Mycobacterium tuberculosis organisms; incomplete Freund's adjuvant, emulsions that include mycobacterial cell wall components; emulsions that include squalene (MF-59), detoxified endotoxins, lipid A derivatives, including A-microbial monophosphoryl lipid (MPL); haptens; protein absorbed in nitrocellulose; saponins, including particle immunomodulators, isolated from the bark of Quillaja saponoria, for example, QS21; endogenous human immunomodulators; adjuvants derived from bacteria, including unmethylated CpG dinucleotides; oligodeoxynucleotides (e.g., synthetic oligonucleotides) containing unmethylated CpG dinucleotides; liposomes (e.g., liposomes made of biodegradable materials, such as phospholipids); biodegradable polymer microspheres (e.g., microspheres made from a variety of polymers, such as polylactic-co-glycolic acid (PLGA), polyphosphazene and polyanhydrides); Interlukin-2, Bacillus Calmette-Guerin; granulocyte monocyte colony stimulating factor; Montanide ISA-51, keyhole limpet hemocyanin; DNA, proteins, encapsulated antigens, immunity stimulating complexes (ISCOM), cholera toxin, cholera toxin derivatives, Zonula occludens toxin; thermolabile enterotoxin of Escherichia coli, labile toxin, labile toxin derivatives, pertussis toxin, pertussis toxin derivatives, muramyl dipeptide derivatives, septic series of adjuvants of montanide, poly-di (carboxylatophenoxy) phosphazene, and lengthening factor of leishmania . When administering the immunogenic composition herein, in conjunction with another adjuvant, the adjuvant polynucleotide may be administered in conjunction with another adjuvant, the adjuvant polynucleotide may be administered before and / or after, and / or simultaneously with, the other adjuvant. For example, the adjuvant polynucleotide can be administered with the initial administration of the antigen, after which a booster dose of vaccine comprising either or both adjuvants is administered. Alternatively, the initial dose of vaccine administered may exclude polynucleotide adjuvants, but an immunogenic substance comprising the adjuvant polynucleotide is subsequently administered to the patient. In certain embodiments, the present immunogenic composition can be administered with cytokines or other co-stimulatory molecules, for example: IL-1, IL-2, IL-4, IL-5, IL-6, IL-7, IL-10 , IL-12, IL-15. In a related embodiment of the present invention, an immunogenic substance comprising a PIKA adjuvant, one or more antigenic substances, plus a suitable carrier is provided. The carrier can be, for example, an oil in water emulsion, a suspension, a lipid carrier, aluminum salt, cochleates, ISCOM, liposomes, live bacterial vectors, live viral vectors, microspheres, nucleic acid vaccines, polymers, rings polymeric, sodium fluoride, transgenic plants, virosomes, virus-like particles and other delivery vehicles known in the art. The adjuvant polynucleotide can be administered directly to the subject or it can be co-administered with a delivery complex. When the supply complex is a substance associated with a means of management, for example, a molecule that results in increased affinity binding to the target cell, such as dendritic cell surfaces and / or increased cell uptake by target cells. Examples of the delivery complexes include, but are not limited to: delivery nucleic acids, associated with: a sterol, (e.g., cholesterol), a lipid (e.g., cationic lipid, virosome, or liposome), or an agent specific binding to the target cell (eg, a ligand recognized by a specific receptor of the target cell). Preferred complexes may be sufficiently stable in vivo to prevent significant decoupling, prior to internalization by the target cell. However, the complex can be decomposable under the appropriate conditions, within the cell. In one embodiment of interest, the composition comprising the PIKA adjuvant does not include poly-L-lysine or a derivative thereof.

The equipment In certain embodiments, the invention provides a kit or kit comprising an immunogenic composition herein. In certain embodiments, the invention provides a kit comprising a PIKA adjuvant and an antigen, in separate formulations. In certain embodiments, the invention provides a kit or kit comprising the adjuvant polynucleotide and an immunogenic compound. In a related embodiment, the invention provides a kit comprising the adjuvant polynucleotide and an immunogenic compound; wherein the immunogenic substance is an antigen. In some embodiments, the kit herein comprises an immunogenic composition herein, in a sterile (eg, aqueous) liquid formulation, wherein the formulation is sterile and is provided in a sterile container, a sterile vial or a syringe sterile In some embodiments, a kit of the present invention comprises an immunogenic composition, formulated for injection. In some embodiments, a kit of the present invention comprises an immunogenic composition of the present invention in a sterile liquid formulation, contained within a sterile syringe, and a needle. In some embodiments, a kit of the present invention comprises an immunogenic composition of the present invention in a sterile liquid formulation in a unit dose amount (eg, a single dose), contained within a sterile syringe, and a needle. In some embodiments, the kit herein comprises an immunogenic composition, lyophilized herein, and in a sterile container, and a container comprising a sterile liquid for reconstitution of the lyophilized composition. In some embodiments, a kit or kit of the present invention comprises an immunogenic composition formulated for rectal, nasal, oral (including inhalation), ophthalmic, topical, pulmonary, ocular or transdermal administration, and an appropriate delivery device, eg, a inhaler, a suppository, an applicator or the like. A kit of the present, in some embodiments, will additionally include instructions for its use, including, for example, dosage amounts and dosing frequencies. The instructions, in some modalities, are printed directly on the case. In other modalities, the instructions are provided on a printed material, such as an insert in the package. The instructive can also be provided in other media, for example, electronically, digitally or analogically, for example, in an audio cassette, on an audio tape, on a compact disc, on a digital versatile disc, and the like.

The formulations An immunogenic composition of the present is provided in any of a variety of formulations. For example, an immunogenic composition can be prepared herein as a liquid solution of dry, injectable powder, for example, an aqueous or saline solution, or as a suspension, a cream, an emulsion, a tablet, a coated tablet, a microcapsule a suppository, drops, pills, granules, dragee, capsule, gel, syrup or suspension. In some embodiments, an immunogenic composition of the present for mucosal delivery is formulated, for example, delivery by means of inhalation, delivery via the respiratory tract, oral delivery, rectal supply, vaginal delivery, etc. The preparation of formulations of a desired immunogenic composition is described generally in Vaccine, 4a. edition, by Stanley A. Platkin and co-authors, W. B. Saunders Company, 4th. edition, 2003. Suitable formulations are also described, for example, in A. Gennaro (2000) "Remington: The Science and Practice of Pharmacy, 20th edition, Lippincott, Williams and Wilkins, Pharmaceutical Dosage Forms and Drug Delivery Systems (1999) , H., C. Ansel et al., Eds., 7th edition, Lippincott, Williams and Wilkins, and Handbook of Pharmaceutical Excipient (2000), AH Kibbe et al., eds., 3a. edition, Amer. Pharmaceutical Assoc. An immunogenic composition herein may be microencapsulated, enrobed, coated on gold microscopic particles, contained in liposomes, nebulized in aerosols, formed into pellets for implantation in the skin, or dried on a sharp object (eg, a needle) for be scraped inside the skin. In another embodiment, the immunogenic substance herein can be supplied alone or in conjunction with a dispersion system. In some embodiments, the dispersion system is selected from the group consisting, for example, of macromolecular complexes, nanocapsules, microspheres, beads and lipid-based systems. The lipid-based systems optionally include oil-in-water emulsions, micelles, mixed micelles or liposomes. In certain embodiments, an immunogenic composition herein, comprising the PIKA adjuvant is in the form of an acceptable solution for pharmaceutical use, which may routinely contain concentrations, acceptable for pharmaceutical use, of salt, regulating agents, preservatives, compatible carriers, adjuvants and, optionally, other therapeutic ingredients. The composition may contain additives, for example: disintegrators, binders, coating agents, swelling agents, lubricants, flavors, sweeteners or solubilizers, and the like. In certain embodiments, an immunogenic composition of the present invention comprising the PIKA adjuvant is administered in its net form or in the form of a pharmaceutically acceptable salt. In certain embodiments, the adjuvant composition of PIKA and an immunogenic composition comprising the PIKA adjuvant and an antigenic compound, is freeze-dried (lyophilized) for stability and long-term storage, in solid form. The method of freeze drying is known to those who have experience in the field. In an aspect of particular interest, the invention provides an adjuvant composition or an immunogenic composition, wherein the immunogenic composition or adjuvant composition contained in the immunogenic composition is in solid or liquid form or in solution or in suspension.

For parenteral administration in an aqueous solution, for example, the solution must be suitably regulated, if necessary, and the liquid diluent first becomes isotonic with sufficient saline or glucose. These particular aqueous solutions are especially suitable for intravenous and intraperitoneal administration. In this regard, the sterile aqueous media that can be employed will be those known to those skilled in the art in the light of the present disclosure. Exemplary injection means which may be used in the present invention include a regulator with and without preservatives and dispersing agents, and edible oil, mineral oil, cod liver oil, squalene, mono-, di- or triglyceride , and a mixture of them. In some embodiments, an immunogenic composition of the present will be formulated in specific forms, suitable for mucosal administration. Said forms, both sterile and non-sterile, may include, for example: capsules, liquid solutions, liquid drops, emulsions, suspensions, elixirs, creams, suppositories, gels, capsules, including soft capsules, sprays, inhalants, aerosols, powders, tablets , coated tablets, microcapsules, suppositories, drops, pills, dragees, syrups, suspensions, enemas, granules or troches. Any inert carrier, such as salt or phosphate buffered saline, stabilizers, propellants, encased in a gelatin capsule or in a microcapsule or vector, which aids in mucosal application, or any such carrier, wherein the The compounds used in the method of the present invention have solubility properties suitable for use in the methods of the present invention. The immunogenic composition herein can be administered to an individual by means of a pharmaceutical delivery system for the inhalation route (oral, intratracheal, intranasal). In that manner, an immunogenic composition can be formulated herein in a form suitable for administration by inhalation. The pharmaceutical delivery system is one that is suitable for respiratory therapy by topical administration of a bacterial composition of the present to the mucosa covering the bronchi. This invention can use a system that depends on the power of a compressed gas to expel the bacteria from a container. An aerosol or a pressure pack can be used for that purpose. Thus, in some embodiments, an immunogenic composition of the present is formulated for delivery to a respiratory tissue, for example, by inhalation. In some embodiments, an immunogenic composition of the present is aerosolized to create an aerosol. When used herein, the term "aerosol" is used in its conventional sense, in reference to very fine liquid or solid particles, carried by a propellant gas under pressure, to a site of therapeutic application. When a pharmaceutical aerosol is employed in this invention, the aerosol contains the immunogenic composition, which may be dissolved, suspended or emulsified in a mixture of a fluid carrier and a propellant. The aerosol can be in the form of a solution, a suspension, an emulsion, a powder or a semi-solid preparation. The aerosols used in the present invention are intended for administration as fine solid particles, or as liquid sprays, through the respiratory tract of a subject. Various types of propellers can be used, known to those with experience in the field. Examples of suitable propellants include, but are not limited to, hydrocarbons or other suitable gas. In the case of pressurized aerosol, the dose unit can be determined by providing a value to supply a dosed amount. There are several different types of inhalation methodologies that can be employed in connection with the present invention. An immunogenic composition of the present can be formulated basically in three different types of formulations for inhalation. First, an immunogenic composition can be formulated herein with low boiling propellants. Said formulations are generally administered by conventional metered dose inhalers (MDI). However, conventional MDIs can be modified, so as to increase the ability to obtain a repeatable dosage, using technology that measures the inspiratory volume and the flow velocity of the subject, as discussed in U.S. Patent Nos. 5,404,871 and 5,542,410. Alternatively, the immunogenic composition of the present may be formulated in aqueous or ethanolic solutions, and may be delivered by conventional nebulizers. In some embodiments, such formulations in solution are nebulized using devices and systems such as those described in U.S. Patent Nos. 5,497,763, 5,544,646, 5,718,222 and 5,660,166. Additionally, an immunogenic composition can be formulated to dry powder formulations. Said formulations can be administered by simply inhaling the dry powder formulation, after creating an aerosol spray of the powder. The technology for accomplishing this is described in U.S. Patent No. 5,775,320 and U.S. Patent No. 5,740,794. Formulations suitable for intranasal administration include: nasal sprays, nasal drops, aerosol formulations, and the like. The present invention provides a package for use in the delivery of an immunogenic composition herein within a respiratory tract or respiratory tract of an individual. In general, a package suitable for delivery to a respiratory tract comprises a container containing a flowable formulation, suitable for delivery to the respiratory tract (eg, by inhalation), of an adjuvant polynucleotide as described above, and an antigen In some embodiments the package is a metered dose inhaler, and the adjuvant polynucleotide and the antigen are formulated with a propellant. In some embodiments, an immunogenic composition is formulated as a sustained release formulation (e.g., a controlled release formulation). For example, in some embodiments, an immunogenic composition is formulated herein in the form of pellets or cylinders, and implanted intramuscularly or subcutaneously, as storage injections or as implants. Such implants will generally employ known inert materials, such as biodegradable polymers. Injectable storage forms are made by forming arrays of microcapsules of an immunogenic composition herein, in biodegradable polymers, such as polylactide-polyglycolide. Examples of other suitable biodegradable polymers include: poly (orthoesters) and poly (anhydrides). Injectable storage formulations are also prepared by trapping the composition in liposomes or microemulsions, which are compatible with the body tissue. Delivery release systems also include the following examples: systems based on polymers, microcapsules, lipids, hydrogel release systems, syllable systems, peptide systems, peptide-based systems, wax coatings, compressed tablets, partially fused implants. Other forms of sustained release are known to those skilled in the art. For oral delivery, an immunogenic composition herein, in some embodiments, will include a coating material soluble in enteric medium. Suitable enteric medium-soluble coating material includes: hydroxypropylmethylcellulose acetate succinate (HPMCAS), hydroxypropylmethylcellulose phthalate (HPMCP), cellulose acetate phthalate (CAP), polyvinyl phthalic acetate (PVPA), Eudragit ™, and Shellac. As a non-restrictive example of an adequate oral formulation, an immunogenic composition is formulated herein, together with one or more pharmaceutical excipients, and coated with an enteric coating, such as described in U.S. Patent No. 6,346,269. For example, an immunogenic composition of the present and a stabilizer are applied by coating on a core comprising excipients acceptable for pharmaceutical use, to form a core coated with active agent.; A sub-coating layer is applied to the core coated with active agent, which is then coated with an enteric coating layer. The core includes, in general, pharmaceutically inactive components, such as lactose, a starch, mannitol, sodium carboxymethylcellulose, sodium starch glycolate, sodium chloride, potassium chloride, pigments, alginic acid salts, talc, titanium dioxide, stearic acid, stearate, microcrystalline cellulose, glycerin, polyethylene glycol, triethyl citrate, tributyl citrate, propanil triacetate, dibasic calcium phosphate, tribasic sodium phosphate, calcium sulfate, cyclodextrin and castor oil. Suitable solvents include aqueous solvents. Suitable stabilizers include alkali metals and alkaline earth metals, phosphate bases and salts of organic acid and organic amines. The undercoating layer comprises one or more of: an adhesive, a plasticizer and an anti-tack agent. Suitable anti-flaking agents include: talc, stearic acid, stearate, sodium stearyl fumarate, glyceryl behenate, kaolin and aerosil. Suitable adhesives include polyvinylpyrrolidone (PVP), gelatin, hydroxyethylcellulose (HEC), hydroxypropylcellulose (HPC), hydroxypropylmethylcellulose (HPMC), vinyl acetate (VA), polyvinyl alcohol (PVA), methylcellulose (MC), ethylcellulose (EC), phthalate of hydroxypropylmethylcellulose (HPMCP), cellulose acetate phthalates (CAP), xanthan gum, alginic acid, salts of alginic acid, Eudragit ™, methacrylic acid / methyl methacrylate copolymer, with polyvinyl acetate phthalate (PVAP). Suitable plasticizers include: glycerin, polyethylene glycol, triethyl citrate, tributyl citrate, propanil triacetate, and castor oil. Suitable enteric-soluble coating material includes hydroxypropylmethylcellulose acetate succinate (HPMCAS), hydroxypropylmethylcellulose phthalate (HPMCP), cellulose acetate phthalate (CAP), polyvinyl phthalic acetate (PVPA), Eudragit ™ and Shellac. Suitable oral formulations also include an immunogenic composition herein, formulated with any of the following: microgranules (see, e.g., U.S. Patent No. 6,458,398), biodegradable macromers (see, e.g., U.S. Patent No. 6,703,037) , biodegradable hydrogels (see, for example, Graham and McNeil (1989 Biomaterials, 5: 27-36), biodegradable particulate vectors (see, for example, U.S. Patent No. 5,736,371), bioabsorbable lactone polymers (see, for example, example, the US patent No. 5,631,015); slow-release protein polymers (see, for example, U.S. Patent No. 6,699,504, Pelias Technologies, Inc.); a block copolymer of poly (lactide-co-glycolide / polyethylene glycol (see, for example, U.S. Patent No. 6,630,155, Atrix Laboratories, Inc.); a composition comprising a biocompatible polymer and particles of metal cation stabilized agent, dispersed within the polymer (see, for example, U.S. Patent No. 6,379,701; Alkermes Controlled Therapeutics, Inc.); and microspheres (see, e.g., U.S. Patent No. 6,303,148; Octoplus, BV.) Suitable oral formulations include also an immunogenic composition herein, formulated with any of the following: a carrier, such as Emisphere® (Emisphere Technologies, Inc.); TIMERx, a hydrophilic matrix combining xanthan gums and locust bean gums which, in the presence of dextrose, forms a strong binder gel in water (Penwest), Germinex ™ (Penwest), Procise ™ (GlaxoSmithKine), SAVIT ™ (Mistral Pharma Inc.), RingCap ™ (Alza Corp.), Smartrix® (S) martrix Technologies, Inc ); SQZgel ™ (MacroMed, Inc.); Geomatriz ™ (Skye Pharma, Inc.); Oros® Tri-layer (Alza Corporation); and similar. Also suitable for use are formulations such as those described in U.S. Patent No. 6,296,842 (Alkermes Controlled Therapeutics, Inc.); and U.S. Patent No. 6,187,330 (Scios, Inc.); and similar. Also suitable for use herein are formulations comprising an intestinal absorption enhancing agent. Enhancers of intestinal absorption include, but are not limited to: calcium chelators (eg, citrate, ethylenediaminetetraacetic acid); surfactants, for example, sodium dodecylsulfate, bile salts, palmitoylcarnitine, and the sodium salts of fatty acids); toxins (for example, Zonula occludens toxin) and the like. In a related embodiment, an immunogenic composition of the present is formulated with one or more agents that inhibit degradation, by gastrointestinal enzymes and / or gastrointestinal acids. In some embodiments, an immunogenic composition is formulated herein with one or more agents that protect the components of the composition against degradation by enzymes and / or gastrointestinal acids. In some embodiments, an immunogenic composition of the present is formulated with one or more agents that enhance absorption by the mucosal tissues. In some embodiments, an immunogenic composition is formulated herein for vaginal delivery, providing a vaginal delivery system. In an exemplary embodiment, the vaginal delivery system is a buffer or a buffer-like device, comprising an immunogenic composition herein. Buffers for drug delivery are known in the art, and any buffer can be used in conjunction with a drug delivery system herein. Buffers for drug delivery are described, for example, in U.S. Patent No. 6,086,909. If a buffer or a buffer-like device is used, there are numerous methods by which an immunogenic composition can be incorporated into the device. For example, the immunogenic composition of the present can be incorporated into a bioadhesive gel-like reservoir at the tip of the device. Alternatively, the immunogenic composition herein may be in the form of a powder material, located at the tip of the buffer. The immunogenic composition herein can also be absorbed into fibers, at the tip of the buffer, for example, by dissolving the immunogenic composition herein in a pharmaceutically acceptable carrier, and absorbing the immunogenic composition present in the fibers of the buffer. The immunogenic composition of the present can also be dissolved in a coating material which is applied to the tip of the buffer. Alternatively, the immunogenic composition of the present can be incorporated in an insertable suppository, which is placed in association with the tip of the tampon. In other embodiments, an immunogenic composition is formulated herein for use with a vaginal ring, providing a vaginal delivery system that is a vaginal ring. The vaginal rings usually consist of an inert elastomeric ring, coated with another elastomer layer containing an immunogenic composition herein. You can easily insert the rings, leave them in place for a desired period of time (for example, up to seven days), then they can be withdrawn by the user. The ring may optionally include a third, external, rate-controlling layer, which contains no immunogenic composition. The immunogenic composition herein can be incorporated into the polyethylene glycol, through the elastomeric silicone ring, to act as a reservoir for the immunogenic composition herein. In other modalities, a suitable vaginal delivery system is a vaginal sponge. The immunogenic composition of the present is incorporated into a silicone matrix, which is coated on a cylindrical, drug-free polyurethane vaginal sponge, as described in the literature. Diaphragms, tablets and suppositories are other examples of drug delivery systems that can be used in the present invention. These systems have been described extensively in the literature. Another system is a container comprising an immunogenic composition of the present (e.g., a tube) that is adapted to be used with an applicator, e.g., for rectal or vaginal delivery. An immunogenic composition of the present is incorporated in creams, lotions, foams, paste, ointments and gels, which can be applied to the vagina, using an applicator. The processes for preparing pharmaceutical products in the formats of cream, lotion, foam, paste, ointment and gel can be found in the literature. An example of a suitable system is an ordinary, fragrance-free lotion formulation containing glycerol, ceramides, mineral oil, petrolatum, parabens, fragrance and water, such as the product sold under the JERGENS ™ brand (Andrew Jergens Co., Cincinnati, Ohio, USA). Suitable non-toxic systems, acceptable for pharmaceutical use, to be used in the compositions of the present invention, will be apparent to those of ordinary skill in the art of pharmaceutical formulations, and examples are described in Remington's Pharmaceutical Sciences, 19a . edition, AR Gennaro, ed., 1995. The selection of suitable carriers will depend on the exact nature of the particular vaginal dosage form desired, for example, if the active ingredient or active ingredients are to be formulated (s) in a cream, lotion, foam, ointment, paste, solution or gel, as well as the identity of the ingredient or active ingredients. Other suitable delivery devices are those described in U.S. Patent No. 6,476,079.

The methods In one aspect of particular interest, the invention provides a method for eliciting and / or enhancing immune responses to an antigenic compound, comprising administering to a host an immunogenic composition herein. In some modalities, the guest is a human. In other embodiments, the host is a non-human animal, for example, a non-human mammal, a bird species, etc. Additionally, the present invention provides a method for increasing the immune responses to an antigenic compound by administering to a host an immunogenic composition herein. The host can be a human or a non-human animal. The subject can be exposed to the antigen through environmental contact and, therefore, at the risk of developing, for example, an allergic reaction, an infectious disease, an autoimmune disease or a cancer. In other embodiments, the subject, for example, has an infectious disease, an autoimmune disease, a cancer or an allergy, as a result of prior exposure to an antigen through environmental contact. In certain embodiments, the adjuvant is administered together with the antigen. In other embodiments, the adjuvants are administered before or after administration of the antigen.

In some embodiments, an immunogenic composition of the present will be administered by mucosal administration. Mucosal administration includes administration to the respiratory tissue, for example, by inhalation, nasal drops, eye drops, etc.; oral administration, anal or vaginal routes of administration, for example, by suppositories, and the like. In an aspect of particular interest, the invention provides a method for enhancing immunological responses to an antigenic compound, comprising administering to an host an immunogenic composition for enhancing the antigenicity of an antigenic compound comprising the adjuvant polynucleotide composition. In some of these modalities, the guest is human. In other embodiments, the host is a non-human animal (e.g., a non-human primate, a rodent or other non-human mammal, a species of bird, etc.). In certain embodiments, the adjuvant polynucleotide composition can be used in the context of a vaccine. Optionally, the vaccine composition contains additional adjuvants. The classes of vaccines included are against respiratory, digestive, genitourinary infectious diseases; sensory diseases, allergy and against autoimmune diseases. An immunogenic composition of the present is administered in an "effective amount", ie, an amount of an immunogenic composition herein, that is effective in a selected route of administration, to elicit, induce or enhance an immune response.

In some embodiments, an immune response is elicited to the antigens produced by a pathogenic microorganism. In some embodiments, the amount of an immunogenic composition herein is effective to limit an infection, and / or to eradicate an infection, and / or to reduce a symptom associated with an infection, by a pathogenic organism. For example, in some embodiments, administration of an immunogenic composition of the present to an individual is effective to treat an infectious disease, wherein treating an infectious disease comprises one or more of the following: reducing the number of pathogens present in the individual (for example, reduce viral load, reduce bacterial load, reduce the number of protozoa, reduce the number of helminths) and / or reduce a parameter associated with the infectious disease, including, but not limited to: reduction of the level of a product produced by the infectious agent (e.g., a toxin, an antigen and the like); and reducing an undesirable physiological response to the infectious agent (e.g., fever, tissue edema and the like). The exact amount of said compositions, required, will vary from one subject to another, depending on the species, age, weight and general conditions of the subject, the severity of the disease, the infection, or the condition being treated or preventing; the particular compound used, its mode of administration, and the like. An appropriate amount can be determined by one who has ordinary experience in the field, using only routine experimentation given the teachings herein. After an initial administration, subjects may receive one or more booster immunizations, spaced appropriately. In some embodiments, serial doses of an immunogenic composition are administered. In those embodiments, the first dose of an immunogenic composition herein may be as a result of the administration of a vaccine. The second dose of an immunogenic composition herein is administered to the individual after the individual has been immunologically enrolled by exposure to the first dose. Reinforcement may be given a few days, weeks or months after the initial immunization, depending on the response and the patient's condition. For example, the booster dose is administered from about 2 days to about 12 months after the initial dose; for example, from about 2 days to about 7 days, from about 1 week to about two weeks, from about two weeks to about four weeks, from about four weeks to about eight weeks, about eight weeks to about six months, or about six months to about 12 months, after the initial dose. The present invention further contemplates the use of a third, fourth, fifth, sixth or subsequent booster immunization using, for example, a third, fourth, fifth, sixth or subsequent dose. In certain embodiments, the administration means may comprise a combination of alternative routes; for example: the dose administered systemically (for example, by peritoneal, intramuscular, subcutaneous or intradermal administration) may be followed by a dose delivered mucosally (for example, intranasal, inhalation) or vice versa. At least one of the doses administered as part of the general protocol would comprise the PIKA adjuvant. In certain embodiments, the adjuvant polynucleotide can be administered either with the first dose of antigen administered, or with any subsequent dose, administered, or at all doses administered to the patient. In certain embodiments, the composition of the immunogenic composition administered may vary between the original administration and the boost and / or between the booster doses. By way of example, the original dose administered may comprise a DNA vaccine; while the booster dose is in the form of a recombinant protein vaccine. At least one of the doses administered as part of the general protocol would comprise the PIKA adjuvant. Whether an antibody response to an antigen has been induced or enhanced in an individual is easily determined using common and current assays. For example, immunological assays may be used, such as enzyme-linked immunosorbent assays (ELISA), radioimmunoassays (RIAs), immunoprecipitation assays, and protein spot analyzes ("Western" spots) and analyzes neutralization (e.g., neutralization of viral infectivity in an in vi tro or in vivo assay), to detect the presence of antibody specific for a microbial antigen in a body fluid, or other biological sample, e.g., serum, a secretion or other fluid, of an individual. That a CD4 immune response has been induced to an antigen in an individual, is easily determined using common and current analyzes, for example, fluorescence activated cell sorting (FACS) (see, for example, Waldrop and coauthors (1997) J) Clin Invest. 99: 1739-1750); intracellular cytokine analysis, which detects cytokine production after stimulation with antigen (see, for example, Suni and co-authors (1998) J. "Immunol., Methods 212: 89-98; Nomura and coauthors. (2000) Cytometry 40: 60-68; Ghanekar and coauthors (2001) Clin.

Diagnostic Lab. Immunol. , 8: 628-631); by MHC-peptide multimeric spotting analysis, for example, the use of soluble MHC class II / peptide multimers (e.g., fluorescently labeled) (see, e.g., Bill and Kotzin (2002) Arthri tis Res. , 4: 261-265; Altman and coauthors (1996) Science 274: 94-96; and Murali-Krishna and co-authors (1998) Immuni ty 8: 17-187); by enzyme-linked immunoscreen analysis (ELISPOT) (see, for example, Hutchings and coauthors (1989), J. Immunol. Methods, 120: 1-8; and Czerkinsky and co-authors (1983) J. "Immunol. 109-121), and the like As a non-limiting example of intracellular cytokine analysis, whole blood is stimulated with antigen and costimulatory antibodies (eg, anti-CD28, anti-CD49d) for two hours or more, Brefeldin A is added to In order to inhibit cytokine secretion, cells are processed for analysis in FACS, using fluorescently labeled antibodies, to CD4 and to cytokines, such as THF-a, IFN-ga ma and IL-2.

It can be determined whether a CD8 response specific for the antigen (eg, cytotoxic T cell (CTL ") was induced to an antigen (eg, to a pathogen), using any of numerous assays known in the art, including, but without limitation to them: measuring the specific lysis by CTL of target cells, which express the antigen on its surface, said target cells having incorporated a detectable label, which is released from the target cells after lysis, and which can be measure using, for example, a 51 Cr release assay, a fluorescence based cytolysis assay of lanthanide, and the like.

Suitable Subjects for Treatment Suitable subjects for treatment with a method hereof for inducing an immune response to a microbial pathogen, and methods for treating or preventing an infection with a microbial pathogen, include individuals who had been infected with a microbial pathogen. pathogenic microorganism; individuals who are susceptible to infection by a pathogenic microorganism, but who have not yet been infected; and individuals who are at risk of becoming infected with a pathogenic microorganism, but who have not yet been infected. Suitable subjects include: infants, children, adolescents and adults. Suitable subjects for treatment with a method hereof for inducing an immune response to a microbial pathogen, and methods for treating or limiting an infection with a microbial pathogen, include the pediatric target population, eg, individuals between one year of age and about 17 years of age, including infants (for example, from about one month of age to about one year of age; children (for example, from about 1 year of age to about 12 years of age; of age) and adolescents (for example, from about 13 years of age to about 17 years of age) .The subjects are suitable for treatment with a method of this to induce an immune response to a microbial pathogen, and methods for Treating or limiting an infection with a microbial pathogen include neonates, for example, an individual (e.g., a human neonate) from one day to about 14 days of age, e.g. about 1 day to about 2 days of age; from about two days to about ten days of age, or from around ten days to about 14 days of age. In a particular embodiment, the subject is a human child of about ten years or less, for example, about five years of age or younger, and the immunogenic compositions are administered in one or more of the following times: two weeks, one month, two months, three months, four months, five months, six months, seven months, eight months, nine months, ten months, eleven months, twelve months, 15 months, 18 months or 21 months after birth; or at 2 years, 3 years, 4 years, 5 years, 6 years, 7 years, 8 years, 9 years, or 10 years of age. In some embodiments, an immunogenic composition of the present is administered to an individual on the age scale of about six months to about six years; wherein the individual receives a first dose at approximately six months of age, and subsequent booster doses, for example, two to three subsequent booster doses, for example, at two years of age, four years of age, and six years old In a particular embodiment, the subject is a human adult from about 17 years of age to 49 years of age. In some modalities, the subject is an elderly human adult, 50 to 65 years of age, 65 to 75 years of age, 75 to 85 years of age or over 85 years of age. In some embodiments, an immunogenic composition of the present is administered to an individual shortly after having been in contact (e.g., shortly after a confirmed or suspected contact) with a real or potential source of the microbial pathogen, e.g., an individual. who knows he has or suspects having an infection with a microbial pathogen. For example, in some embodiments, an immunogenic composition of the present is administered to an individual within about 1 hour, within about 2 hours, within about 5 hours, within about 8 hours, within about 12 hours, within about 18 hours, within about 24 hours, within about 2 days, within about 4 days, within about 7 days, within about 2 weeks or within about a Month after having been in contact with an individual known to have or suspected of having an infection with a microbial pathogen. In some embodiments, an immunogenic composition of the present is administered to an individual who is known or suspected of being a carrier of a microbial pathogen, whether or not it exhibits symptoms of the infection. Suitable subjects for treatment with a method hereof for inducing an immune response to a microbial pathogen, and methods for treating or limiting an infection with a microbial pathogen, include individuals deficient in CD4 + T cells ("CD4 + deficient individuals"). ), for example, individuals who have lower than normal numbers of functional CD4 + lymphocytes. As used herein, the term "normal individual" refers to an individual having levels and function (s) of CD4 + T lymphocyte within the normal scale of the population, for humans, typically from 500 to 1500 CD4 + T lymphocytes per mm3 of blood. Individuals deficient in CD4 + include individuals who have an acquired immunodeficiency or a primary immunodeficiency. An acquired immunodeficiency may be a temporary deficiency of CD4 +, such as that caused by radiation therapy or chemotherapy. Also suitable for treatment with the methods of the invention are individuals with intact, healthy immune systems, but who are at risk of becoming deficient of CD44 ("at-risk" individuals). Individuals at risk include, but are not limited to, individuals who are more likely than the general population to become deficient in CD4 +. Individuals at risk of becoming deficient in CD4 + include, but not limited to, individuals who are at risk of HIV infection due to sexual activity with HIV-infected individuals; intravenous drug users; individuals who may have been exposed to blood infected with HIV, blood products or other body fluids contaminated with HIV; a baby that has passed through the natural birth canal of an individual infected with HIV; babies that are being fed by mothers infected with HIV; and similar. Suitable subjects for treatment with the formulations and methods of the present invention for treating allergy include any individual who has been diagnosed as having an allergy. The appropriate subjects for treatment using the methods and agents described herein, include individuals known to have allergic hypersensitivity to one or more allergens. Appropriate subjects for treatment include those who have any of the allergic disorders mentioned above. Subjects who are at risk of having an allergic reaction to one or more allergens are also suitable for the treatment. Individuals who fail treatment with one or more common therapies to treat an allergic disorder are also suitable. Suitable subjects for treatment include individuals living in industrialized nations; individuals living in developing countries; individuals who live in rural areas; individuals living in relatively isolated areas, and the like. The target population for an immunogenic composition herein will vary, depending on the microbial pathogen. The foregoing description generally describes the present invention. The following examples will be of assistance in the understanding of the present invention. These examples are described solely for purposes of illustration, and are not intended to limit the scope of the invention.

Changes of form and substitution of equivalents are contemplated, that the circumstances could suggest or return expedients. Even though specific terms have been used here, these terms are intended to have a descriptive meaning and not purposes of limitation.

EXAMPLES EXAMPLE 1 Systemic immune response induced by peritoneal and mucosal administration of PIKA in combination with a SARS antigen This example demonstrates that the immunogenic substance comprising PIKA and a SARS antigen induces a strong systemic immune response when administered by peritoneal injection, and a strong immune response, both in local and remote sites of administration, for example, both immunological responses are elicited. mucosal as systemic when administered mucosally. Six groups of Balb / c mice were inoculated with a SARS antigen composition plus the PIKA adjuvant (a heterogeneous composition of PIKA molecules, predominantly within a weight scale distribution of about 66 kDa to 1,200 kDa). The amount of antigen and adjuvant used is described in Tables A to C below. A repeated inoculation was administered after two weeks, and an additional booster was administered after another two weeks. In week six, a blood sample was taken and the presence of specific IgA and specific IgG in the blood serum was detected by ELISA. The mice were sacrificed, the lungs were removed, dissected and washed to remove the supernatant. The resulting mucosal extract was tested for the presence of specific S-IgA. The results that are presented in tables A, B and C (also in figures 1, 2 and 3) show that the presence of PIKA in the immunogenic composition administered by intraperitoneal injection intensifies the immune system response, when measured by the increase , dependent on the dose, on the expression of specific IgG in the blood. However, no impact on mucosal immunological activity was observed when it was measured by the presence of specific S-IgA in the samples taken from the lungs. The presence of PIKA in the mucosally administered immunogenic composition enhances the mucosal immune response, when measured by the dose-dependent increase in specific S-IgA expression on the mucosal surfaces of the lungs. Additionally, there was an intensification, dose dependent, in the systemic immune response, when measured by the presence of specific IgA and IgG in the blood serum samples.

TABLE A ELISA detection of specific IgA antibody titers in the murine lung supernatant (diluted 6x), after immunization with vaccines comprising PIKA or alum and / or whole, inactivated SARS antigen.

Units: Average optical density, absorption at 405 nm.

TABLE B Detection by ELISA of specific IgA antibody titers in murine serum (diluted 100x) after immunization with vaccines comprising PIKA or alum, and / or whole, inactivated SARS antigen.

Units: Average optical density, absorption at 405 nm.

TABLE C Detection by ELISA of specific IgG antibody titers in murine serum (diluted l, 000x) after immunization with vaccines comprising PIKA or alum and / or whole, inactivated SARS antigen.

Units: Average optical density, absorption at 405 nm.

EXAMPLE 2 Mucosal and Systemic Immunological Response Induced by the Administration of PIKA in Combination with an Influenza Antigen This example demonstrates that an immunogenic substance comprising PIKA and an influenza antigen induces a strong mucosal immune response, both at the local site and at sites remote from administration; that is, both in the respiratory and intestinal mucosal membranes, as well as a systemic immune response, when administered mucosally. Five groups of Balb / c mice were vaccinated on day zero and day 20, with compositions as described in table D.

TABLE D Vaccine composition and route of administration The influenza antigen used is a VAXIGRIP influenza vaccine, divided, purified, inactivated, of Sanofi Pasteur, which is approved for human use, which comprises strains equal to H1N1, H3N2 and strain b / Shanghai5 / 361/2002. Blood samples were collected after day 35 and tested for the presence of a specific humoral immune response in ELISA. The mice were sacrificed after seven weeks; The lungs and intestines were removed, dissected and washed to remove the supernatant. The resulting mucosal extract was tested for the presence of specific S-IgA in ELISA. The results presented in Table E demonstrate that the presence of PIKA in the mucosally administered immunogenic composition enhances the mucosal immune response in the lungs, when measured by the expression of specific S-IgA on the mucosal surfaces of the lungs.

TABLE E Detection by ELISA of specific S-IgA titers from the murine lung supernatant, after immunization with vaccines comprising PIKA and / or the divided, inactivated influenza antigen.

Units: Average optical density, absorption at 405 nm; NS: Neutral saline solution. Additionally, the results presented in Table F (Figure 5) demonstrate that the presence of PIKA in the mucosally administered immunogenic composition enhances the mucosal immune response in the remote mucosal site of the intestine, when measured by the expression of S- Specific IgA in the mucosal surfaces of the intestine.

TABLE F Detection by ELISA of specific S-IgA titers from the murine gut supernatant, after immunization with vaccines comprising PIKA and / or the divided, inactivated influenza antigen.

Units: average optical density, absorption at 405 nm In addition, the results presented below demonstrate that the presence of PIKA in the mucosally administered immunogenic composition enhances the systemic immune response, when measured by specific IgG expression (Table G, Figure 6 ) and the specific IgA (Table H, Figure 7) in blood serum samples.

TABLE G Units: Average optical density, absorption at 405 nm.

TABLE H Detection by ELISA of specific IgA titers, from murine blood serum, after immunization with vaccines comprising PIKA and / or inactivated, divided influenza antigen, Units: Average optical density, absorption at 405 nm. A suspension of spleen cells was prepared and a sample of the cell suspension of each mouse was placed in 6-12 concavities of the ELISPOT plate and cultured. Each concavity of the ELISPOT plate contained 200 uL of splenocyte suspension, equivalent to approximately 2.5xl05 cells per concavity. For each mouse sample of the cultured splenocytes, half of the concavities containing the splenocytes were incubated with culture medium, and the other half of the concavities was stimulated using the influenza antigen. Plates were incubated at 37 ° C for 20 hours under environmentally controlled conditions, prior to final preparation, and read using an ordinary ELISPOT plate reader. Table I below (see also figure 7) presents the results regarding the number of cells, by concavity, that produce IL-2. It was observed that the administration of the immunogenic substance comprising PIKA and the influenza antigen induces a significantly higher level of cells that produce IL-2, compared to PIKA or the influenza antigen alone. This indicates that the antigen with PIKA induces an immune response mediated by T cells.

TABLE I Detection by ELISPOT of murine splenocytes that produce IL-2 after immunization with PIKA and / or the divided influenza antigen, inactivated.

Units: Average number of cells that produce IL-2 by 2.5 x 105 splenocytes.

EXAMPLE 3 Mucosal and systemic immune response induced by the administration of PIKA in combination with an influenza antigen This example demonstrates that an immunogenic substance comprising PIKA and an influenza antigen induces a strong humoral, mucosal and systemic immunological response, specific for the antigen, and an immunological response of T cells, after their administration to the mucosal surface. Five groups of Balb / c mice were immunized (three per group) on day zero, day 14 and day 30, with compositions as described in the tables that follow. The influenza antigen used is a divided, purified, inactivated VAXIGRIP influenza vaccine from Sanofi Pasteur, which is approved for human use, comprising strains similar to H1N1, H3N2 and strain b / Shanghai5 / 361/2002. Blood samples were collected 14 days after the third immunization and tested for the presence of a specific IgG in the serum, by means of ELISA. The mice were sacrificed 14 days after the third immunization; The lungs and intestines were removed, dissected and washed to remove the supernatant. The resulting supernatant was tested for the presence of specific S-IgA by means of ELISA. The results presented in Table J (Figure 9) demonstrate that the presence of PIKA in the mucosally administered immunogenic composition enhances the mucosal immune response in the lungs, when measured by specific S-IgA expression on the mucosal surfaces of lungs. Immunization with Al (OH) 3 and the antigen, by intranasal route, did not induce the production of S-IgA on the mucosal surface of the lungs.

TABLE J Detection by ELISA of specific S-IgA in the lung supernatant (dilution: 32x) after immunization with vaccines comprising PIKA or Al (OH) 3 adjuvant and / or inactivated divided influenza.

Units: Average optical density value The results presented in Table K (Figure 10) demonstrate that the presence of PIKA in the mucosally administered immunogenic composition enhances the mucosal immune response in the intestine, when measured by the expression of S- Specific IgA in the mucosal surfaces of the intestine. Immunization of Al (OH) 3 with antigen, intranasally, did not induce the production of S-IgA on the mucosal surface of the intestine.

TABLE K ELISA detection of specific S-IgA in the intestine supernatant (dilution: 32x) after immunization with vaccines comprising PIKA or Al (OH) 3 adjuvant and / or inactivated, divided influenza antigen.

Units: Average optical density value A suspension of spleen cells was prepared and a sample of the cell suspension of each mouse was placed in 6 concavities of the ELISPOT plate and cultured; each concavity of the ELISPOT plate contained 200 uL of splenocyte suspension, equivalent to approximately 3.0 x 10 5 cells per concavity. For each mouse sample of cultured splenocytes, half of the concavities containing the splenocytes were incubated with culture medium; and the other half of the concavities was stimulated using the influenza antigen. Plates were incubated at 37 ° C, 5 percent C02 for twenty hours, before final preparation and reading using an ordinary ELISPOT plate reader. Table L below (see also Figure 11) presents the results for the number of cells per 1.0 x 106 splenocytes that produce interferon-gamma. It was observed that the administration of the immunogenic substance comprising PIKA and the antigen of the influence induced a significantly higher level of interferon-gamma producing cells, compared to PIKA or with the influenza antigen alone.

TABLE L Detection by ELISPOT of murine splenocytes that produce interferon-gamma, after immunization with PIKA and / or with the divided influenza antigen, inactivated.

Units: Number of cells that produce interferon-gamma by 1.0 x 106 splenocytes. Table M below (see also Figure 12) presents the results for the number of cells per 1.0 x 106 splenocytes that produce IL-2. It was observed that the administration of the immunogenic substance comprising PIKA and the influenza antigen induced a significantly higher level of cells that produce IL-2, compared to PIKA or with the influenza antigen alone.

Units: Number of cells that produce IL-2 by 1.0 x 106 splenocytes. The ability of PIKA to induce an amplified production of interferon-gamma and IL-2 by splenocytes indicates that the immunization of antigen with PIKA, intranasally, and by subcutaneous injection, induces a strong immune response mediated by T cells. immunization with Al (OH) 3 and the antigen, intranasally, does not promote the T cell response that promotes the antigen alone. However, the addition of Al (OH) 3 to the antigen does not promote an enhanced immune response of T cells, when administered intranasally or by subcutaneous injection.

Claims (11)

1 CLAIMS

1. - An immunogenic composition comprising: (a) an adjuvant polynucleotide comprising: a polyriboinosinic-polyribocytidylic acid (PIC), at least one antibiotic and at least one positive ion; and (b) at least one antigen; wherein the composition is formulated for mucosal administration.

2. The immunogenic composition according to claim 1, wherein the composition comprises: heterogeneous compositional molecules of the adjuvant polynucleotide composition, for molecular weight, wherein the molecular weight is at least 66,000 daltons.

3. The immunogenic composition according to claim 1 or claim 2, wherein the composition comprises heterogeneous molecules of the adjuvant polynucleotide composition, for molecular weight, wherein the molecular weight is from about 66,000 to 1,200,000 dalton.

4. The immunogenic composition according to any of claims 1 to 3, wherein the composition comprises heterogeneous molecules of the adjuvant polynucleotide composition, for molecular weight, wherein the molecular weight is at least 150,000 dalton.

5. The immunogenic composition according to any of claims 1 to 4, wherein the immunogenic composition additionally comprises at least one immunomodulator.

6. The immunogenic composition according to any of claims 1 to 5, wherein the immunogenic composition additionally comprises at least one agent that enhances mucosal absorption.

7. - The immunogenic composition according to any of claims 1 to 6, wherein the immunogenic composition or the adjuvant comprised in the immunogenic composition, are in the form of a liquid, a liquid solution, liquid drops, a solid, capsules, emulsions, suspensions, elixirs, creams, suppositories, gels, soft capsules, sprays, inhalants, aerosols, tablets, coated tablets, pills, dragees, powders, syrup, thick suspension, microcapsules, enemas, granules or troches.

8. - The immunogenic composition according to any of claims 1 to 7, wherein at least one of the adjuvant composition or the immunogenic composition is freeze-dried.

9. The immunogenic composition according to any of claims 1 to 8, wherein the immunogenic composition is administered by inhalation, rectal supply, vaginal delivery, nasal delivery, oral delivery, pulmonary delivery, ophthalmic supply, topical delivery, delivery ocular or transdermal supply.

10. The immunogenic composition according to any of claims 1 to 9, for use in enhancing the mucosal immunogenic response of a host. The use of the immunogenic composition or the adjuvant comprised in the immunogenic composition, according to any of claims 1 to 10, in the preparation of a medicament for enhancing the mucosal immunogenic response of a host. 12. The use according to claim 11, wherein the medicament is for enhancing a mucosal immune response at a local site and a remote site. 13. The use of the immunogenic composition or the adjuvant comprised in the immunogenic composition, according to any of claims 1 to 10, in the preparation of a medicament for inducing an immune response mediated by T cells, in a host. 14. - The use according to any of claims 11 to 13, wherein the medicament is administered by inhalation, by rectal supply, vaginal supply, nasal delivery, oral supply, pulmonary supply, ophthalmic supply, topical delivery, ocular delivery or transdermal supply. 15. The use according to any of claims 11 to 14, wherein the host has an infectious disease, and administration of the antigenic compound elicits an immunological response against the pathogen causing the infectious disease. 16. A kit comprising the immunogenic composition according to any of claims 1 to 10. 17. A delivery system comprising an immunogenic composition according to any of claims 1 to 10, wherein the system of delivery enhances the supply of the immunogenic composition to the mucosal surface. 18. A method for enhancing a mucosal immune response comprising administering to an host an immunogenic composition according to any of claims 1 to 10. 19. The method according to claim 18, wherein the host has an immunogenic composition. infectious disease, and administration of the antigenic compound elicits an immunological response against the pathogen causing the infectious disease. 20. A method for enhancing a mucosal immune response at a local site and at a remote site, comprising administering to an host an immunogenic composition according to any of claims 1 to 10. 21.- A method for inducing a response T-cell-mediated immunology, which comprises administering to a host an immunogenic composition according to any of claims 1 to 10. 22. The use according to any of claims 11 to 15, or the method of conformance with any of claims 18 to 21, wherein the host is a human. 23. Use according to any of claims 11 to 15, or the method according to any of claims 18 to 21, wherein the host is a non-human animal.