CN110507819A - Application of the Artesunate as immunologic adjuvant in preparation rabies vacciness - Google Patents

Application of the Artesunate as immunologic adjuvant in preparation rabies vacciness Download PDF

Info

Publication number
CN110507819A
CN110507819A CN201910745298.1A CN201910745298A CN110507819A CN 110507819 A CN110507819 A CN 110507819A CN 201910745298 A CN201910745298 A CN 201910745298A CN 110507819 A CN110507819 A CN 110507819A
Authority
CN
China
Prior art keywords
artesunate
adjuvant
art
rabies
vaccine
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
CN201910745298.1A
Other languages
Chinese (zh)
Other versions
CN110507819B (en
Inventor
郭霄峰
何红玲
罗均
张月
刘青
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
South China Agricultural University
Original Assignee
South China Agricultural University
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by South China Agricultural University filed Critical South China Agricultural University
Priority to CN201910745298.1A priority Critical patent/CN110507819B/en
Publication of CN110507819A publication Critical patent/CN110507819A/en
Application granted granted Critical
Publication of CN110507819B publication Critical patent/CN110507819B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • 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
    • A61K39/12—Viral antigens
    • 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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • 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
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2760/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses negative-sense
    • C12N2760/00011—Details
    • C12N2760/20011—Rhabdoviridae
    • C12N2760/20111—Lyssavirus, e.g. rabies virus
    • C12N2760/20134—Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • Virology (AREA)
  • Veterinary Medicine (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Mycology (AREA)
  • Immunology (AREA)
  • Microbiology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Epidemiology (AREA)
  • Oncology (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Communicable Diseases (AREA)
  • Molecular Biology (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)

Abstract

The present invention provides application of the Artesunate as immunologic adjuvant in preparation rabies vacciness, and present invention firstly provides artemisinin derivative Artesunate (ART) is used as rabies vacciness adjuvant.The present invention passes through experimental studies have found that artemisinin derivative Artesunate (ART) is as rabies vacciness adjuvant can significantly increase its immunogenicity, can be used as new semple type rabies vaccine candidate adjuvant.The Artesunate (ART) of vaccine effect studies have shown that relatively low-dose of the invention can promote the immune effect of rabies vacciness, can reduce the cost of production vaccine.Vaccine effect studies have shown that artemisinin derivative Artesunate (ART) of the invention can generate better protection as rabies vacciness adjuvant.

Description

Application of the Artesunate as immunologic adjuvant in preparation rabies vacciness
Technical field
The invention belongs to molecular biosciences field of immunology.It is being prepared more particularly, to Artesunate as immunologic adjuvant Application in rabies vacciness.
Background technique
Hydrophobin (Rabies virus, RABV) is the strong people beast caused with the characteristics of infecting central nervous system Suffer from the rabic cause of disease of infectious disease altogether, once morbidity, lethality are up to 100%.China is rabic district occurred frequently, number of the infected It is only second to India, is in second place of the world.With the increase of domestic pets, the rabic control in China human world and prevention and treatment are still appointed Weight road is remote.However rabies pathogenesis is also imperfectly understood so far, also without treating rabic specific drug, so prevention is mad The most effective measure of dog disease is timely vaccine inoculation.
Currently, be both at home and abroad the protein formulation purified for the rabies vacciness of the mankind, due to a lack of corresponding adjuvant, first It is secondary it is immune need to inject 3-5 needle, take one month.As for animal rabies vaccine, import inactivated vaccine have using it is safe, be easy to The advantages such as preservation, pollution-free danger.Although China's approved several moneys inactivated vaccines with independent intellectual property rights at present, because The factors such as higher of production-scale limitation and production cost, these inactivated vaccines hair more backward for Asia and African economy Price is too high for area in exhibition, limits them in the use of developing country, and most of economically developed city is still Preferred import inactivated vaccine.Domestic inactivated vaccine needs for animals further reduce the cost.
Summary of the invention
The defects of higher the technical problem to be solved by the present invention is to overcome existing vaccine cost and deficiency, provide Artesunate As application of the immunologic adjuvant in preparation rabies vacciness.
The object of the present invention is to provide Artesunate (referred to as (ART)) as active constituent in preparation rabies vacciness adjuvant In application.
By ART and hydrophobia strain mixed immunity mouse, immune in mouse of enhancing inactivation hydrophobin is answered It answers.And the recruitment evaluation of vaccine after identifying and mixing with vaccine, experimental result hair are further carried out as vaccine adjuvant to ART Existing, Artesunate can significantly increase the immunogenicity of rabies vacciness, can be used as new semple type rabies vaccine candidate adjuvant.
In one embodiment of this invention, the Artesunate is as sole active agent.
The present invention also provides a kind of rabies vacciness adjuvant, the rabies vacciness adjuvant includes Artesunate.
In one embodiment of this invention, the Artesunate is as sole active agent.
The present invention also provides application of the Artesunate in preparation rabies vacciness, and the Artesunate is as adjuvant.
The present invention also provides a kind of vaccine compositions, and it includes the hydrophobin strains and Artesunate of inactivation.
In one embodiment of this invention, the hydrophobin strain of the inactivation is selected from CVS-11 strain, rHEP-dG poison Strain, SAD plants, CTN-1 plants, PV plants, at least one of FluryLEP plants.Certainly, above-mentioned strain, all rabies diseases are not limited to Poison strain is suitable for the present invention.
In one embodiment of this invention, in the vaccine composition hydrophobin strain and Artesunate amount ratio It is 0.9 × 105~1.1 × 105The μ of FFU:120~130 g.
In one embodiment of this invention, the content of hydrophobin strain is 1.0 × 10 in the vaccine composition5~ 1.1×105The μ of FFU:120~130 g.
In one embodiment of this invention, the dosage of Artesunate is 5 μ g/g the weight of animals in the vaccine composition.It is green The dosage of artemisic succinate is determined according to the weight of animals such as mouse, and by taking mouse as an example, actual use concentration is 5 μ g/g mouse weights, If every mouse weight is about 25g, the dosage of Artesunate is about 125 μ g.
In one embodiment of this invention, further include dimethyl sulfoxide (DMSO), other solvents can also be used, DMSO exists When dissolving the reagent of some good water solubilities, solute effect is more preferable.
In one embodiment of this invention, Artesunate (g) in the vaccine composition: dimethyl sulfoxide (mL)=1:(8 ~12), preferably 1:10.
It in one embodiment of this invention, further include PBS buffer solution.PBS buffer solution has effects that physiological saline, in stabilization More advantageous, pH 7.20-7.40 in terms of albumen.
In one embodiment of this invention, by volume, Artesunate in the vaccine composition: PBS buffer solution=1: (90~110), preferably 1:100.
The present invention also provides application of the Artesunate in preparation rabies vacciness.The rabies vacciness is for preventing or controlling Treat people or the rabies of other animals.
Optionally, the Artesunate is as adjuvant.
Term " adjuvant " is the pharmacy or immunological reagent or composition for changing other agent efficacies, refer in a broad sense from Body does not provide wide spectrum substance that is immune, but can increasing the immunogenicity of the antigen of co-administration.Adjuvant can be added to vaccine In, increase the quantity and lasting protection of antibody by increasing immune response, to reduce the external of injection to the maximum extent Substance.Adjuvant can also be used for improving the effect of vaccine, be changed by helping to the immune anti-of certain types of immune system cell It answers, for example, according to the purpose of vaccine, by activating T cell rather than the B cell of secretory antibody.Therefore, adjuvant can be advantageously Adjust cytokine-expressing/secretion, antigen presentation, type of immune response etc..In the present invention, the situation of the term refers to work For the compound or composition of the carrier or auxiliary substance of immunogene and/or other drugs reactive compound.
Wherein above-mentioned " antigen ", which is typically meant that, can be identified by immune system and can for example be adapted to by being formed to be used as Property immune response a part antibody or antigen specific T-cell come trigger antigen specific immune reaction substance.Antigen It is divided into two classes: comlete antigen and incomplete antigen according to property.Comlete antigen (complete antigen) abbreviation antigen, is one The existing immunogenicity of class, and have immunoreactive substance, such as most protein, bacterium, virus, bacterial exotoxin and intestines poison Element etc..Incomplete antigen, that is, haptens (hapten) is that only have immunoreactivity, and the substance of non-immunogenicity, such as absolutely mostly The hydrolysate and all lipoids of number polysaccharide (capsular polysaccharide of such as pneumococcus), capsular polysaccharide.
The invention has the following advantages:
Present invention firstly provides artemisinin derivative Artesunate (ART) is used as rabies vacciness adjuvant.
The present invention passes through experimental studies have found that artemisinin derivative Artesunate (ART) can be shown as rabies vacciness adjuvant The immunogenicity for writing enhancing rabies vacciness, can be used as new semple type rabies vaccine candidate adjuvant.
The Artesunate (ART) of vaccine effect studies have shown that relatively low-dose of the invention can promote exempting from for rabies vacciness Epidemic disease effect can reduce the cost of production vaccine.
Vaccine effect studies have shown that artemisinin derivative Artesunate (ART) of the invention is used as rabies vacciness adjuvant Better protection can be generated.
Detailed description of the invention
Fig. 1 is shown as a kind of chemical formula of artemisinin derivative Artesunate (ART).
Fig. 2, which is shown as ART, influences statistical chart to KM mouse weight, while setting up PBS control group.
Peripheral blood anti-rabies virus neutralizing antibody water after mouse is immunized in the CVS-11 that Fig. 3 is shown as combining ART inactivation Flat statistical chart, while setting up PBS control group (P < 0.05 *).
Peripheral blood anti-rabies virus neutralizing antibody water after mouse is immunized in the rHEP-dG that Fig. 4 is shown as combining ART inactivation Flat statistical chart, while setting up PBS control group (P < 0.05 *).
Fig. 5 is shown as the survival rate statistical chart of CVS-11 attack mouse after ART is immunized mouse 14 days as vaccine adjuvant.
Specific embodiment
The present invention is further illustrated below in conjunction with Figure of description and specific embodiment, but embodiment is not to the present invention It limits in any form.Unless stated otherwise, the present invention uses reagent, method and apparatus routinely try for the art Agent, method and apparatus.
Unless stated otherwise, following embodiment agents useful for same and material are commercially available.
Currently, the World Health Organization is recommended to use inactivation rabies vacciness according to its safety, in order to develop it is more effective and Cheaper inactivated vaccine, we, which can take, improves the means such as virus titer or the better adjuvant of searching.
Fig. 1 is shown as the chemical formula of artemisinin derivative Artesunate (ART) used by following embodiment, Artesunate (ART) No. CAS is 88495-63-0, molecular formula: C19H28O8, molecular weight: 384.42, No. EINECS: 618-170-5.
Artesunate used in following embodiment is purchased from TCI AmericaPortland company (Tokyo chemical conversion industry Co., Ltd.).
Artemisinin derivative Artesunate (ART) adjuvant in following embodiment, is the CVS-11 or rHEP-dG with inactivation Strain is mixed with ART, forms rabies virus vaccine.
Specifically: ART is initially dissolved in DMSO, and the CVS-11 in PBS with inactivation is dissolved in when then using in vivo Or rHEP-dG hydrophobin mixing.According to Artesunate (g): DMSO (mL)=1:10 ratio, the i.e. Artesunate of 1g are molten In 10mL DMSO, the Artesunate being then dissolved in DMSO is redissolved in PBS buffer solution solution, Artesunate and PBS The volume ratio of buffer is 1:100, and PBS buffer solution is phosphate buffer, pH 7.2-7.4.
Use the ART as adjuvant, rabies vacciness induction can be promoted to generate in higher anti-rabies virus and anti- Body, and better protecting effect is generated, reduce the cost of Canine vaccine.
Specifically, in the immunologic adjuvant, Artesunate is the dosage and 1.0 × 10 by 5 μ g/g mouse weights5FFU inactivation CVS-11 or rHEP-dG mixing, by right leg gastrocnemius intramuscular injection be immunized mouse after collect peripheral blood, utilize neutralize experiment Study anti-rabies virus neutralize antibody titers.
In addition, artemisinin derivative Artesunate (ART) also exists in the application as vaccine adjuvant or in terms of preparing vaccine Within protection scope of the present invention.
Artemisinin derivative Artesunate (ART) is initially dissolved in DMSO, is dissolved in PBS when then using in vivo In, it is used after being mixed with CVS-11 the or rHEP-dG hydrophobin of inactivation.The immunologic adjuvant Artesunate is by 5 μ g/g Dosage is mixed with the CVS-11 of inactivation or rHEP-dG, collects serum after mouse is immunized by right leg gastrocnemius intramuscular injection, is used Neutralize experiment detection anti-rabies virus neutralize antibody titers.The present invention is also to ART side effect, ART Adjuvanted vaccines immunogenicity It is studied with the biological characteristics such as malicious protection are attacked, to assess the safety and effect of its as vaccine adjuvant.The results show that ART will not generate significant side effect as new vaccine adjuvant in Mice Body, and ART can significantly increase vaccine as adjuvant Immunogenicity promotes vaccine-induced body to generate the anti-rabies virus neutralizing antibody with Vaccine effectiveness, can preferably protect Protect the attack that body resists lethal rabies virus.
In terms of specific research method, the present invention utilizes immunology the relevant technologies, has studied in Mice Body ART as novel The recruitment evaluation of vaccine adjuvant.
Embodiment 1
The research that novel rabies virus vaccine adjuvant ART influences mouse weight
SPF grade Kunming (KM) mouse of 3-4 week old is divided into 2 groups, i.e. ART group and PBS control group, every group comprising 6 small Mouse.ART is injected with the dosage of 5 μ g/g by the right leg gastrocnemius muscle of mouse, and control group injects equivalent PBS.It is every after administration The weight of its detection mouse, monitors 15 days altogether.By the weight before respectively injecting on the weight ratio of all mouse, weight ratio is studied Example situation of change.As shown in Figure 2, the results showed that, ART not will lead to treatment mouse weight and mitigate, this is similar to PBS treatment.More Importantly, there is not abnormal symptom in treatment mouse.Therefore, the ART treatment that dosage is 5 μ g/g is safe to mouse.
Embodiment 2
Artesunate (ART) in the intracorporal immunogenicity of KM mouse and attacks malicious Protective strategy to rabies vacciness
1, experimental method
CVS-11 and rHEP-dG are inactivated with UV respectively.Then ART is mixed with the CVS-11 of inactivation or rHEP-dG, PBS is used as vehicle control.The SPF grade kunming mouse of 6~7 week old is divided into 4 groups, i.e., ART+CVS-11 group, PBS+CVS-11 group, ART+rHEP-dG group and PBS+rHEP-dG control group, every group includes 6 mouse.The right leg gastrocnemius injection of every mouse of experimental group 1.0×105The hydrophobin of FFU inactivation and the mixture of ART, the volume of mixture are 200 μ L, and ART's contains in mixture Measuring is 5 μ g ART/g mouse weights, Artesunate (g): dimethyl sulfoxide (mL)=1:10, by volume, Artesunate: PBS Buffer=1:100, control group intramuscular injection penetrate 1.0 × 105The hydrophobin of FFU inactivation and PBS mixture.7th after immune It and the 14th day acquisition peripheral blood, and by fluorescence antibody virus neutralization (FAVN) testing inspection serum anti-rabies virus And antibody level, rabies standard serum are purchased from the World Health Organization (WHO), detection method is in strict accordance with world animal health Organize the standard practice instructions of (World Organisation for Animal Health, OIE).
2, experimental result
As shown in Figure 3, the results showed that, the hydrophobin that mouse generates is immunized with the CVS-11 joint ART of inactivation and neutralizes Antibody level is significantly higher than PBS control group.As shown in figure 4, the mad dog that mouse generates is immunized with the rHEP-dG joint ART of inactivation Sick virucidin's level is significantly higher than PBS control group.
Fig. 3 and Fig. 4's the result shows that, when ART is applied to rabies vacciness as adjuvant, it is not limited to a certain specific Inactivation hydrophobin strain, but can be adapted for the hydrophobin strain of various inactivations.
3, further, in order to verify after mouse obtains high level immunity whether there is protection to strong virus attack, In CVS-11 strain living is passed through intramuscular injection infecting mouse by 14d after immune, while being arranged without immune rabies vacciness Control group, the morbidity and death condition of continuous 3 weeks observation mouse, records survival rate daily.As shown in Figure 5, the results showed that, it uses ART as adjuvant mouse than there is higher survival rate with the mouse of PBS control.
The above results show that artemisinin derivative Artesunate (ART) enhances inactivation rabies epidemic disease when being used as adjuvant The immune response of seedling.
The above embodiment is a preferred embodiment of the present invention, but embodiments of the present invention are not by above-described embodiment Limitation, other any changes, modifications, substitutions, combinations, simplifications made without departing from the spirit and principles of the present invention, It should be equivalent substitute mode, be included within the scope of the present invention.

Claims (9)

1. application of the Artesunate as active constituent in preparation rabies vacciness adjuvant.
2. rabies vacciness adjuvant according to claim 1, which is characterized in that the Artesunate as sole active at Point.
3. a kind of rabies vacciness adjuvant, which is characterized in that the rabies vacciness adjuvant includes Artesunate.
4. rabies vacciness adjuvant according to claim 3, which is characterized in that Artesunate is as sole active agent.
5. application of the Artesunate in preparation rabies vacciness, which is characterized in that the Artesunate is as adjuvant.
6. a kind of vaccine composition, which is characterized in that it includes the hydrophobin strains and Artesunate of inactivation.
7. vaccine composition according to claim 6, which is characterized in that the hydrophobin strain of the inactivation is selected from At least one of CVS-11 strain, rHEP-dG strain.
8. vaccine composition according to claim 6, which is characterized in that hydrophobin strain in the vaccine composition Amount ratio with Artesunate is 0.9 × 105~1.1 × 105The μ of FFU:120~130 g.
9. vaccine composition according to claim 8, which is characterized in that hydrophobin strain in the vaccine composition Amount ratio with Artesunate is 1.0 × 105~1.1 × 105The μ of FFU:120~130 g.
CN201910745298.1A 2019-08-13 2019-08-13 Application of artesunate as immunologic adjuvant in preparation of rabies vaccine Active CN110507819B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201910745298.1A CN110507819B (en) 2019-08-13 2019-08-13 Application of artesunate as immunologic adjuvant in preparation of rabies vaccine

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201910745298.1A CN110507819B (en) 2019-08-13 2019-08-13 Application of artesunate as immunologic adjuvant in preparation of rabies vaccine

Publications (2)

Publication Number Publication Date
CN110507819A true CN110507819A (en) 2019-11-29
CN110507819B CN110507819B (en) 2021-02-19

Family

ID=68625709

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201910745298.1A Active CN110507819B (en) 2019-08-13 2019-08-13 Application of artesunate as immunologic adjuvant in preparation of rabies vaccine

Country Status (1)

Country Link
CN (1) CN110507819B (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114983999A (en) * 2022-06-09 2022-09-02 四川大学 New application and verification method of artemisinin and derivatives thereof

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1758905A (en) * 2003-02-12 2006-04-12 乔治敦大学 Use of artemisinin for treating tumors induced by oncogenic viruses and for treating viral infections
WO2010105096A2 (en) * 2009-03-11 2010-09-16 University Of Massachusetts Modulation of human cytomegalovirus replication by micro-rna 132 (mir132), micro-rna 145 (mir145) and micro-rna 212 (mir212)
WO2014124430A1 (en) * 2013-02-11 2014-08-14 Emory University Nucleotide and nucleoside therapeutic compositions and uses related thereto
CN109675027A (en) * 2017-10-18 2019-04-26 辽宁成大生物股份有限公司 A kind of rabies vacciness adjuvant, vaccine composition and its application

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1758905A (en) * 2003-02-12 2006-04-12 乔治敦大学 Use of artemisinin for treating tumors induced by oncogenic viruses and for treating viral infections
CN103393672A (en) * 2003-02-12 2013-11-20 乔治敦大学 Use of artemisinin for treating tumors induced by oncogenic viruses and for treating viral infections
WO2010105096A2 (en) * 2009-03-11 2010-09-16 University Of Massachusetts Modulation of human cytomegalovirus replication by micro-rna 132 (mir132), micro-rna 145 (mir145) and micro-rna 212 (mir212)
WO2014124430A1 (en) * 2013-02-11 2014-08-14 Emory University Nucleotide and nucleoside therapeutic compositions and uses related thereto
CN109675027A (en) * 2017-10-18 2019-04-26 辽宁成大生物股份有限公司 A kind of rabies vacciness adjuvant, vaccine composition and its application

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
EGERUAN B. IMOUKHUEDE等: "LOW-LEVEL MALARIA INFECTIONS DETECTED BY A SENSITIVE POLYMERASE CHAIN REACTION ASSAY AND USE OF THIS TECHNIQUE IN THE EVALUATION OF MALARIA VACCINES IN AN ENDEMIC AREA", 《AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE》 *
李小雯等: "青蒿琥酯抗病毒作用的研究进展", 《临床医药文献杂志》 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114983999A (en) * 2022-06-09 2022-09-02 四川大学 New application and verification method of artemisinin and derivatives thereof

Also Published As

Publication number Publication date
CN110507819B (en) 2021-02-19

Similar Documents

Publication Publication Date Title
JP2562827B2 (en) Adjuvant mixture
KR20180054629A (en) Methods and compositions for immuno-protection against over-the-pathogenic E. coli
JP5848243B2 (en) Immunogenic composition against dengue virus
Dhungyel et al. Footrot vaccines and vaccination
James et al. The influence of adjuvant on induction of protective immunity by a non-living vaccine against schistosomiasis.
Marcinkiewicz et al. Eliminating factor H-binding activity of Borrelia burgdorferi CspZ combined with virus-like particle conjugation enhances its efficacy as a Lyme disease vaccine
CN107073097A (en) Double adjuvant vaccine compositions, preparation and use
CN107296955B (en) Immunogenic bordetella bronchiseptica compositions
KR100447297B1 (en) Improved Inactivated Vaccine
Relyveld et al. [3] Preparation of vaccines by the action of glutaraldehyde on toxins, bacteria, viruses, allergens, and cells
KR0162074B1 (en) Solutions containing antigen and zinc hydroxide or iron hydroxide as an adjuvant and processes for preparing such solutions
TWI648063B (en) Composition and method for immunization against C. difficile
CN110507819A (en) Application of the Artesunate as immunologic adjuvant in preparation rabies vacciness
CN100572532C (en) A kind of duck plague vaccine and special strains thereof
Sampath et al. An immunogenicity study of a newly introduced purified Vero cell rabies vaccine (Abhayrab) manufactured in India
Grubhofer An adjuvant formulation based on N-acetylglucosaminyl-N-acetylmuramyl-L-alanyl-D-isoglutamine with dimethyldioctadecylammonium chloride and zinc-L-proline complex as synergists
Hosty et al. Human antirabies gamma globulin
CN110179975B (en) Vegetable oil vaccine adjuvant and preparation method and application thereof
Panse et al. Passive immunity in experimental cholera
CN101717779B (en) Fusion protein suitable for anthrax antitoxin and vaccines
WO2016036503A1 (en) Antigen compositions and methods of use for treating extraintestinal pathogenic e. coli infections
DK2376113T3 (en) PREPARATIONS AND DOSAGE REGIMES WHICH INCLUDES A CLOSTRIDIUM VACCINE AND levamisole
Heneine et al. Stepwise iodination. A general procedure for detoxification of proteins suitable for vaccine development and antiserum production
CN103154013A (en) Trisaccharide derivates, and their use as adjuvants
Veeraraghavan et al. The value of duck-embryo vaccine and high-egg-passage Flury vaccine in experimental rabies infection in guinea-pigs

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant