CA2183260A1 - Prolactin as a vaccine adjuvant - Google Patents

Prolactin as a vaccine adjuvant

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Publication number
CA2183260A1
CA2183260A1 CA002183260A CA2183260A CA2183260A1 CA 2183260 A1 CA2183260 A1 CA 2183260A1 CA 002183260 A CA002183260 A CA 002183260A CA 2183260 A CA2183260 A CA 2183260A CA 2183260 A1 CA2183260 A1 CA 2183260A1
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Prior art keywords
prolactin
composition
human
vaccine
cdna
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Abandoned
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CA002183260A
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French (fr)
Inventor
Susan Richards
Johanne Kaplan
Richard Moscicki
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Genzyme Corp
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Individual
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7088—Compounds having three or more nucleosides or nucleotides
    • A61K31/711—Natural deoxyribonucleic acids, i.e. containing only 2'-deoxyriboses attached to adenine, guanine, cytosine or thymine and having 3'-5' phosphodiester links
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/39—Medicinal preparations containing antigens or antibodies characterised by the immunostimulating additives, e.g. chemical adjuvants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/04—Immunostimulants
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/575—Hormones
    • C07K14/57554—Prolactin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
    • A61K2039/53—DNA (RNA) vaccination
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
    • A61K2039/55511—Organic adjuvants
    • A61K2039/55516—Proteins; Peptides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Organic Chemistry (AREA)
  • Epidemiology (AREA)
  • Molecular Biology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Immunology (AREA)
  • Biochemistry (AREA)
  • Genetics & Genomics (AREA)
  • Engineering & Computer Science (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Zoology (AREA)
  • Endocrinology (AREA)
  • Biotechnology (AREA)
  • Mycology (AREA)
  • Oncology (AREA)
  • Communicable Diseases (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Biophysics (AREA)
  • Toxicology (AREA)
  • Microbiology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Virology (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)

Abstract

The present invention relates to a composition for enhancing the immune response of an animal to an infectious disease vaccine wherein the composition comprises prolactin. Preferably, the composition is human prolactin and the animal to be vaccinated is, as well, human. The present invention further relates to a composition for enhancing the immune response of an animal to an infectious disease vaccine wherein the composition comprises prolactin cDNA. Human prolactin cDNA is preferred.

Description

PROLACTIN AS A VACCINE ADJUVANT

Background of the Invention The use of vaccines to prevent diseases in humans, farm livestock, sports animals and household pets is a common practice, and considerable effort has been, and is being, made to extend this practice to cover a more extensive array of diseases to which these patients are subject. For example, the use of rabies vaccine in animals is by now commonplace, and efforts are being made to obtain suitable vaccines to immunize animals against other dise~ses.
One problem that frequently is encountered in the course of active immunization is that the antigens used in the vaccine are not sufficiently immunogenic to raise the antibody titer to sufficient levels to provide protection against subsequent challenge or to maintain the potential for mounting these levels over extended time periods. Another problem is that the vaccine may be deficient in inducing cell-mediated immunity which is a primary immune defense against bacterial and viral i nfection .
In order to obtain a stronger humoral and/or cellular response, it is common to administer the vaccine in a formulation containing an adjuvant, a material which enhances the immune response of the patient to the vaccine. The most commonly used adjuvants for vaccines are oil preparations and alum. The mechanisms by which such adjuvants function are not understood, and whether or not a particular adjuvant preparation will be sufficiently effective in a given instance is not predictable.
In addition, with the advent of gene therapy it has been reported that some success has been accomplished with using genes or "naked DNA" as vaccines. However, as with some of the conventional vaccines, the immune response obtained was insufficient to afford immunization.

WO 95/21625 ~ 18 ~ 2 6 0 PCT/US95/01866 Accordingly, there is a need for additional effective adjuvant preparations which are suitable for potentiating vaccines for animals in general, and particularly in humans.

5 Summary of the Invention `
The present invention relates to a composition for enhancing the immune response of an animal to an infectious disease vaccine wherein the composition comprises prolactin.
Preferably, the composition is human prolactin and the animal 1C to be vaccinated is, as well, human.
The present invention further relates to a composition for enhancing the immune response of an animal to an infectious disease vaccine wherein the composition comprises prolactin cDNA. Human prolactin cDNA is preferred.
In another aspect, the invention relates to a method of enhancing the immune response of a subject animal to an infectious disease vaccine comprising co-administering an effective amount of prolactin or prolactin cDNA along with a vacci ne .

Brief Description of the Drawing Figure 1 shows the amino acid sequence for the prolactin protein .
Figure 2 shows the nucleic acid sequence for the 25 prolactin cDNA.
Figure 3 is a graph illustrating the Bovine serum albumin (BSA)-specific antibody response of rats immunized with BSA
alone or BSA + prolactin.
Figure 4 is a graph illustrating a comparison of the BSA-30 specific proliferative response of rat PBL, at 101 day timepoint, between four rats receiving BSA alone versus BSA +
prolactin .

WO 95/21625 ~ 2 6 0 PCT/US95/01866 Detailed Description of the Invention Definitions As used herein, "prolactin" refers to a polypeptide 5 obtained from tissue cultures or by recombinant techniques and other techniques known to those of skill in the art, exhibiting the spectrum of activities characterizing this protein. The word includes not only human prolactin (hPRL), but also other mammalian prolactin such as, e.g., mouse, rat, rabbit, primate, 0 pig and bovine prolactin. The amino acid sequence of a recombinant hPRL is shown in Figure 1. The recombinant PRL
(r-PRL) is preferred herein.
The term "recombinant prolactin", designated as r-PRL, preferably human prolactin, refers to prolactin having 15 comparable biological activity to native prolactin prepared by recombinant DNA techniques known by those of skill in the art.
In general, the gene coding for prolactin is excised from its native plasmid and inserted into a cloning vector to be cloned and then inserted into an expression vector, which is used to 20 transform a host organism. The host organism expresses the foreign gene to produce prolactin under expression conditions.
As used herein, the term "adjuvant" has its conventional meaning, i.e., the ability to enhance the immune response to a particular antigen. Such ability is manifested by a significant 25 increase in immune-mediated protection. Furthermore, the term "genetic adjuvant" refers to prolactin cDNA which comprises the complement to the DNA sequence encoding the prolactin protein as defined above. The sequence for prolactin cDNA is shown in Figure 2.
General Method Formulations containing prolactin for adjuvant purposes are most conveniently administered by intramuscular or subcutaneous injections or intraperitoneal although other 35 methods of administration are possible.

Standard formulations are either liquid injectables or solids which can be taken up in suitable liquids as suspensions or solutions for injection. Suitable excipients are, for example, water, saline, dextrose, glycerol, ethanol, and so forth.
5 Nontoxic auxiliary substances, such as wetting agents, buffers, or emulsifiers may also be added. m Sustained and continuous release formulations are of considerable variety and could be used i'rr~'the method of the present invention, as is understood by those skilled in the art.
Prolactin can be administered separately from the vaccine or in combination with the vaccine. When prolactin is combined with the vaccine, the composition administered contains an immunogen that is effective in eliciting a specific response to a given pathogen or antigen, a pharmaceutically acceptable vaccine carrier and an immunopotentiating amount of prolactin. The vaccine will normally be administered per manufacturer's instructions. Other adjuvants may be administered either with the vaccine or together with the prolacti n .
Prolactin will typically be used to enhance the protection afforded by animal or human vaccines that are considered "weak" (i.e., provide diminished protection in terms of level, extent, and/or duration). Examples of such vaccines are bacterins such as Pseudomonas Staphylococcal, Enterotoxin Streptococci, cytomegalovirus, HIV, Bordetella bacterin, Escherichia coli bacterins, Haemophilus bacterins, Leptospirosis vaccines, Moraxella bovis bacterin, Pasteurella bacterin and Vibrio fetus bacterin and attenuated live or killed virus products such as bovine respiratory disease vaccine (infectious bovine rhinotracheitis, parainfluenza-3, respiratory syncytial virus), bovine virus diarrhea vaccine, equine influenza vaccine, feline leukemia vaccine, feline respiratory disease vaccine (rhinotracheitis-calicipneumonitis viruses), canine parvovirus vaccine,transmissible gastroenteritis vaccine, pseudorabies vaccine, and rabies vaccine.

WO 95/21625 ~ 1 8 3 ~ 6 0 PCT/US95/01866 In addition, because we have demonstrated in vitro and in vivo data that indicate that prolactin can enhance the immune response to an immunogen and thereby function as a vaccine adjuvant, it is believed that the exogenous administration of 5 the prolactin gene would result in the expression of prolactin in vivo which would be available to function as an adjuvant to any immunogen whether administered through conventional means or via gene inoculation. The "genetic adjuvant" could be produced by inserting prolactin cDNA into a DNA delivery 0 vehicle (e.g., plasmid vectors, liposomes, viral vectors). This could be accomplished as described by Pellegrini 1., et al., Molec. Endocrinolgy, 6, 1023 (1992), Maniatis T., et al., Molecvlar Cloning: A Laboratory Manual, 2nd Edition, Cold Spring Harbor Press (1989) and Felger P., et al., Proc. Natl.
Acad. Sci., 84, 7413, (1991). The "genetic adjuvant" is then administered along with either cDNA encoding the immunogen in an appropriate delivery vehicle or "naked" (i.e., solely the cDNA). In addition, the "genetic adjuvant" could be administered along with the immunogen itself. The injection 20 sequence would be optimized per immunogen, i.e., the prolactin cDNA could be co-administered with the immunogen or immunogen cDNA, or administered in advance or subsequent to their administration. It is believed that the prolactin cDNA
could be inserted into the same DNA delivery vehicle. Various 25 routes of administration could be used.

Co-mitogenicity of recombinant human prolactin (r-hPRL) Peripheral blood Iymphocytes (PBL) were isolated from 30 the blood of normal human volunteers by density gradient centrifugation on Ficoll Paque (Pharmacia). Heparinized blood was diluted 3 fold in phosphate-buffered saline (PBS) and centrifuged at 2000 rpm for 20 minutes. The buffy coat, located on the surface of the red blood cell pellet and 35 consisting of white blood cells, was collected and diluted with an equal volume of PBS. The diluted buffy coat was layered on ~183~60 WO 95/21625 ~CT/US95/01866 Ficoll Paque (6 mls of buffy coat on 4 mls of Ficoll Paque in a 15 ml tube) and centrifuged for 30 minutes at 1400 rpm. The PBL layer, found at the Ficoll-plasma interface, was collected and the cells were washed three times in PBS. PBL were then resuspended at 2x106/ml in serum-free AIM-V medium from Gibco and added to the wells of round bottom 96 well microtiter plates in a 100 ~LI volume (2x105 PBL/well).
A suboptimal dose of the T cell mitogen concanavalin A
(Con A; 0.2 ~g/ml) was added in a 50 ,ul volume together with 0 50 ~l of varying concentrations of r-hPRL (0-1000 ng/ml final). Cultures were done in triplicate. The cells were incubated at 37'C/5% CO2 for 72 hours and the amount of proliferation measured by tritiated thymidine incorporation.
Tritiated thymidine (0.5~1 Ci/well) was added for the last 18 hours of incubation and cell-associated radioactivity was measured by scintillation counting after harvesting the cells onto glass fiber filters using a Skatron 96 well cell harvester.
Results, obtained with cells from different individuals, shown in Table 1 below, indicated that r-hPRL was able to enhance the proliferative response of T Iymphocytes to a suboptimal concentration of Con A. This co-mitogenic activity was best observed with r-hPRL concentrations of 1 -10 ng/ml, illustrated in Figure 3.

Tab/e 1 Co-mitogenic activity of recombinant human prolactin (cpm +/- SEM) Con A + r-hPRL (ng/ml) Donor 1 Donor 2 Donor 3 No prolactin 22323+4585 35942+810 16549+1618 0.1 22949+2003 34040+1446 17083+1895 35882+3665 45839+2137 27590i3151 1 0 32832+1972 37658+150 22991 +2358 100 25963+4855 35009i2105 22674+1662 1000 23990 1534 35921 +1690 26646+2574 WO 95t21625 ~ 18 3 2 fi O PCT/US95/01866 Enhancement of antigen-specific proliferation by r-hPRL
To test the ability of r-hPRL to enhance the proliferative 5 response of human T cells to a specific antigen, PBL were incubated with various concentrations of r-hPRL and streptokinase, a common antigen to which most individuals are exposed. Cultures were performed in triplicate in the wells of 96 well round bottom microtiter plates and consisted of 100 111 PBL (2x105/well), 50 ,ul streptokinase (25 ,ug/ml final) and 50 ~l of r-hPRL at varying concentrations (0-1000 ng/ml final). Proliferation was measured by tritiated thymidine incorporation after 6 days of culture at 37C/5%CO2.
The results, shown in Table 2 below, indicated that r-hPRL, at a concentration of 1 ng/ml, significantly enhanced streptokinase-induced proliferation.

Effect of recombinant human prolactin on streptokinase-specific proliferation Streptokinase + r-hPRL (ng/ml) Proliferation (cpm +/- SEM) No prolactin 31807+4235 0.1 30220+5448 50964+6469 1 0 35620+11318 1 00 36713+2230 1 000 33494+7990 2 1 8 3 2 6 0 PCI~/US95/01866 Effect of prolactin in enhancing the immune response to an immunogen Twenty-four 150 gram male Sprague-Dawley rats were divided into 4 groups. The contro~group received an intraperitoneal injection of 10 ~-,ug BSA mixed with alum. The other 3 groups received intraperitoneal injections of 10 ~9 BSA mixed with alum along with either 180 ~19 prolactin, 375 ~9 prolactin or 750 ,ug prolactin. Tail vein bleeds were taken weekly for 4 weeks and the serum evaluated for antibody to BSA by a Radioimmunosorbent Assay (RIA). The animals were boosted after the 4th bleed with 10,ug BSA mixed with alum.
Tail vein bleeds were taken over a 7 week period to obtain serum which was evaluated for the development of antibody to BSA by RIA.

Bovine serum albumin (BSA)-specific proliferation of peripheral blood Iymphocytes from rats immunized with BSA
+/- r-hPRL
To measure the effect of r-hPRL on the cellular response of rats immunized with BSA, blood was collected from individual animals sacrificed 101 days after boosting. To isolate peripheral blood Iymphocytes (PBL), blood samples were diluted 4 fold in the phosphate-buffered saline (PBS) and centrifuged at 2000 rpm for 20 minutes. The buffy coat was collected and contaminating red blood cells were removed by the addition of Tris-ammonium chloride Iysis buffer followed by a 10 minute incubation at 37C. PBL were then washed twice in PBS and resuspended at 5x106/ml in RPMI-1640 medium supplemented with 100 u/ml penicillin, 100 ,ug/ml streptomycin, 20 mM Hepes buffer, 2 mM L-glutamine, 5x10-5 M 2-mercaptoethanol and 5% heat-inactivated fetal calf serum.
PBL were added to the wells of flat bottom 96 well microtiter plates in a 100 ,ul volume (5x105 cells/well) and cultured in the presence of medium alone (background control) or 1000 !lg/ml BSA added in a 100 ,ul volume. Cultures were done in triplicate. Proliferation was measured by tritiated thymidine incorporation after 5 days of culture at 37C/5% CO2.
The results indicated that, overall, PBL rats immunized with BSA + 180 ,ug rhPRL displayed higher levels of BSA-5 specific proliferation than PBL from rats immunized withantigen alone. This observation suggests that r-hPRL may act to enhance the cellular component of the immune response to an immunizing antigen. Results are compiled in Table 3 below and are illustrated in Figures 5 and 6.

Table 3 BSA-specific proliferation of rat PBL (cpm +/- SEM) 101 days after boosting Group Background BSA-specific response BSA alone Rat 1 918 + 35 1236 + 100 Rat 2 559 + 169 1392 + 185 Rat 3 614 + 51 930 + 265 Rat 4 242 + 21 2122 + 257 BSA + 180 ~9 PRL
Rat 1 426 + 99 2552 + 30 Rat 2 269 + 18 756 i 37 Rat 3 723 + 185 4328 + 77 Rat 4 676 + 29 2023 + 397 2183~60 SEQUENCE LISTING

(l) GENERAL INFORMATION~

5 (i) APPLICANT: Richards,Susan Kaplan, Johanne Moscicki, Richard (ii) TITLE OF INVENTION: PROLACTIN AS ADJUVANT

(iii) NUMBER OF SEQUENCES: 2 (iv) CORRESPONDENCE ADDRESS:
(A) ADDRESSEE: William G. Gosz (B) STREET: One Kendall Square (C) CITY: Ca",bridge (D) STATE: MA
(E) COUNTRY: U.S.A.
(F) ZIP: 02139 (v) COMPUTER READABLE FORM:
(A) MEDIUM TYPE: Floppy disk (B) COMPUTER: IBM PC compatible (C) OPERATING SYSTEM: PC-DOSIMS-DOS
2 5 (D) SOFTWARE: Patentln Release #l .0, Version #l .2 (vi) CURRENT APPLICATION DATA:
(A) APPLICATION NUMBER:
(B) FILING DATE:
3 0 (C) CLASSIFICATION:

(viii) ATTORNEY/AGENT INFORMATION:
(A) NAME: Gosz, William G
(B) REGISTRATION NUMBER: 27,787 (C) REFERENCE/DOCKET NUMBER: GEN 4-2.0 WO 95121625 ~ 18 3 2 6 0 PCTIUS95/01866 (ix) TELECOMMUNICATION INFORMATION:
(A) TELEPHONE: 5088722583 (B) TELEFAX: 6173747225 (2) INFORMATION FOR SEQ ID NO:1:

(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 351 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (iv) ANTI-SENSE: NO

(v) FRAGMENT TYPE: N-terminal 2 0 (Vi) ORIGINAL SOURCE:
(A) ORGANISM: human prolactin (xi) SEQUENCE DESCRIPTION: SEQ ID NO:1:

Thr lle Gly Phe His Met Pro Arg Leu Cys His Glu Cys Lys Phe Arg Met Thr Thr Arg Ala Asn Ser Leu Ala Thr Glu Phe His Met Pro Arg Leu Ser Glu Gln Cys His Glu Cys Lys Phe Arg Met Thr Gly Glu Asn 3 5 Glu Arg Ala Thr Glu Asp Ser Tyr Met Asx Leu Ser Thr His Met Pro ~1~ 3 ~ ~ O PCT/US95/01866 Arg Leu Leu Cys Ser His Met Pro Arg Leu Asx Pro Met Arg Asn Ala 5 Glu Asn Thr Glu Arg Glu Asp Asp Glu Phe lle Asn lle Thr lle Asn 95' :;
His Met Ala Asn Pro Arg Glu Pro Arg Leu Ala Cys Thr lle Asn Pro Arg Leu Met Arg Asn Ala Ala Cys Cys Glu Ser Ser lle Asn His Met Pro Arg Leu Pro Glu Pro Leu Glu Asn Gly Thr His Leu Tyr Cys His Glu Cys Lys His Met Pro Arg Leu Leu Pro lle Cys Pro Gly Gly Ala 2 0 Ala Arg Cys Gln Val Thr Leu Arg Asp Leu Phe Asp Arg Ala Val Val Leu Ser His Tyr lle His Asn Leu Ser Ser Glu Met Phe Ser Glu Phe Asp Lys Arg Tyr Thr His Gly Arg Gly Phe lle Thr Lys Ala lle Asn Ser Cys His Thr Ser Ser Leu Ala Thr Pro Glu Asp Lys Glu Gln Ala Gln Gln Met Asn Gln Lys Asp Phe Leu Ser Leu lle Val Ser lle Leu 3 5 Arg Ser Trp Asn Glu Pro Leu Tyr His Leu Val Thr Glu Val Arg Gly WO 95/21625 ~ 1 8 3 2 6 ~ PCI/US95/01866 Met Gln Glu Ala Pro Glu Ala lle Leu Ser Lys Ala Val Glu lle Glu Glu Gln Thr Lys Arg Leu Leu Glu Gly Met Glu Leu lle Val Ser Gln Val His Pro Glu Thr Lys Glu Asn Glu lle Tyr Pro Val Trp Ser Gly Leu Pro Ser Leu Gln Met Ala Asp Glu Glu Ser Arg Leu Ser Ala Tyr Tyr Asn Leu Leu His Cys Leu Arg Arg Asp Ser His Lys lle Asp Asn Tyr Leu Lys Leu Leu Lys Cys Arg lle lle His Asn Asn Asn Cys (2) INFORMATION FOR SEQ ID NO:2:

(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 1100 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: cDNA

WO 95/21625 2 1 8 3 2 6 0 PCI`/US95/01866 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:2:

CATCCAmC ATCTATTTCT GAGAAGGTCC TTAATGATCC GTTCCATTGC MGCTTCTTT 1020 wo 95/21625 2 1 ~ 3 2 6 0 PCT/USg5/01866 TAGTTGTATC TCTmGMT CCATGCTTGG GTGTMCAGG TCTCCTCTTA MMMTMAA 1080

Claims (16)

Claims
1. A composition for enhancing the immune response of an animal to an infectious disease vaccine, wherein the composition comprises prolactin.
2. The composition of claim 1 wherein the prolactin is human prolactin.
3. A composition for enhancing the immune response in accordance with claim 1 wherein the animal is a human.
4. The composition of claim 1 wherein the prolactin comprises an amino acid sequence selected from all or a portion of the amino acid sequence of Figure 1 (SEQ ID
NO.:1).
5. A composition for enhancing the immune response of an animal to an infectious disease vaccine wherein the composition comprises prolactin cDNA.
6. The composition of claim 5 wherein the prolactin is human prolactin cDNA.
7. A composition for enhancing the immune response in accordance with claim 5 wherein the animal is a human.
8. The composition of claim 5 wherein the cDNA comprises a cDNA sequence selected from all or a portion of the cDNA sequence of Figure 2 (SEQ ID NO.:2).
9. A method of enhancing the immune response of a subject animal to an infectious disease vaccine comprising co-administering an effective amount of prolactin along with a vaccine.
10. The method of claim 9 wherein the prolactin is human prolactin.
11. A method for enhancing the immune response in accordance with claim 9 wherein the animal is a human.
12. The method of claim 9 wherein the prolactin comprises an amino acid sequence selected from all or a portion of the amino acid sequence of Figure 1 (SEQ ID NO.:1).
13. A method of enhancing the immune response of a subject animal to an infectious disease vaccine comprising co-administering an effective amount of prolactin cDNA
along with a vaccine.
14. The method of claim 13 wherein the prolactin is human prolactin.
15. A method for enhancing the immune response in accordance with claim 13 wherein the animal is a human.
16. The method of claim 13 wherein the prolactin comprises an cDNA sequence selected from all or a portion of the cDNA sequence of Figure 2 (SEQ ID NO.:2).
CA002183260A 1994-02-14 1995-02-14 Prolactin as a vaccine adjuvant Abandoned CA2183260A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US19635094A 1994-02-14 1994-02-14
US08/196,350 1994-02-14

Publications (1)

Publication Number Publication Date
CA2183260A1 true CA2183260A1 (en) 1995-08-17

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ID=22725034

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CA002183260A Abandoned CA2183260A1 (en) 1994-02-14 1995-02-14 Prolactin as a vaccine adjuvant

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EP (1) EP0952846A1 (en)
JP (1) JPH09509415A (en)
AU (1) AU700104B2 (en)
CA (1) CA2183260A1 (en)
WO (1) WO1995021625A1 (en)

Families Citing this family (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU2749697A (en) * 1996-04-30 1997-11-19 Genzyme Corporation Use of prolactin as a tgf-beta antagonist
WO1998031385A1 (en) * 1997-01-21 1998-07-23 Genzyme Corporation Enhancement of hematopoietic cells
AU770994B2 (en) 1999-08-25 2004-03-11 Accuplex, L.L.C. Diagnostic assays of secreted biological fluids for detection of infection and inflammatory conditions
NZ518319A (en) 1999-10-22 2004-04-30 Univ Nebraska Nucleic acid molecules encoding serum amyloid A isoforms from mammalian colostrum used to treat and prevent enteric infections
AU2002364507A1 (en) * 2001-11-21 2003-06-10 Board Of Regents Of The University Of Nebraska Mammary-associated serum amyloid a3 promoter sequences and uses for same
US7368546B2 (en) 2003-01-21 2008-05-06 The Board Of Regents Of The University Of Nebraska Human SAA3 nucleic acid molecule, protein, and methods of use for same

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4725549A (en) * 1980-09-22 1988-02-16 The Regents Of The University Of California Human and rat prolactin and preprolactin cloned genes
US5028591A (en) * 1987-09-14 1991-07-02 Pitman-Moore, Inc. Method for stimulating the immune system
GB8821656D0 (en) * 1988-09-15 1988-10-12 Health Lab Service Board Pharmaceutical compositions for eliciting immunostimulant effect

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AU1876595A (en) 1995-08-29
EP0952846A1 (en) 1999-11-03
JPH09509415A (en) 1997-09-22
EP0952846A4 (en) 1999-11-03
AU700104B2 (en) 1998-12-24
WO1995021625A1 (en) 1995-08-17

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