Erfolgreich durch internationale Zusammenarbeit

MORPHOLOGY, PATHOLOGY, PHYSIOLOGY

Cite as: Archiv EuroMedica. 2022. 12; 5: e1. DOI 10.35630/2199-885X/2022/12/5.6

Received 18 August 2022;
Received in revised form 31 August 2022;
Published 12 September 2022

Development of adjuvant compositions for the creation of vaccine preparations

Viktoria Chahirova¹, Dmitriy Kompantsev¹ ,
Anna Chahirova¹ , Larisa Lejneva¹,
Natalia Shabanova¹

¹Pyatigorsk Medical and Pharmaceutical Institute – Branch of Volgograd State Medical University, Pyatigorsk, Russia

download article (pdf)

   annachaxirova@gmail.com

Abstract

In the course of this study, the expediency of using oil adjuvants as part of an antiviral vaccine was established. The choice of excipients is justified. It was found that as auxiliary substances, the most optimal are TEA, lecithin, oleic acid, mannitol. Stable compositions were obtained using TOTAL oils and base oil. A technology for producing oil adjuvant compositions has been developed. The stability of vaccine preparations with the use of oil adjuvant compositions has been studied. The oil adjuvant is convenient in the production process, as it forms a fairly stable emulsion, the vaccine is freely injected. It was found that the most advantageous physical and technological properties for practical use were the vaccine samples with a volume ratio of antigen and adjuvant 40:60.

Keywords: adjuvant, vaccine, oil, emulsifier, stability

Introduction

Avian influenza viruses can infect humans, causing zooanthroponotic infections. Direct contact with infected animals or the environment contaminated with the biological fluids of infected birds is associated with the risk of human infection and can lead to illness (from mild flu-like symptoms to severe acute respiratory illness) or even death of a person [7].

Nowadays, the problem of zooanthroponoses is solved quite simply, there are specially developed vaccines for this, the use of which is a preventive measure and reliable protection for animals and humans [12].

In the fight against various infectious diseases, along with the development of effective vaccines that can cause persistent immunity, it is urgent to further improve existing and develop new substances that can enhance the effect of immunization [4,5].

The use of adjuvants that have an immunostimulating effect is due to the weak immunogenicity of some vaccine preparations [1,2,11]. Nonspecific stimulants are widely used to increase the immunogenicity of antigens, which lose a significant degree of initial immunogenicity during purification [10,13,15].

Currently, dozens of substances of organic and inorganic nature are known that can have an adjuvant effect [8]. Mineral compounds (aluminum oxide hydrate and phosphate gels), polymer substances, complex chemical mixtures (lipopolysaccharides, protein-lipopolysaccharide complexes, etc.); bacteria and bacterial components; lipids and emulsifiers (lanolin, arlacel); substances that cause an inflammatory reaction (saponin, turpentine) and others are used as adjuvants [1, 3, 14].

Purpose of study

Development of non-specific adjuvant stimulants used in industrial immunology.

Materials and methods,

Modern laboratory methods, including biotechnological, technological, and virological, were used to carry out the research.

The mineral oils "Total", "Marcol", base oil Janos VHVI-4, base oil SN-80 were used in the work. The oil adjuvant "Montanid" was used as a comparison. Nonionic emulsifiers were used as emulsifying agents: twin-20, twin-60, twin-80, oleic acid, soy lecithin, triethanolamine, manit, PEG, lanolin, charge, aerosil, etc.

Results and Discussion

Increasing the effectiveness of vaccines is often achieved through the use of non-specific stimulants. Despite the existing achievements, the development of promising adjuvants continues. To date, in medical and veterinary practice, most vaccines contain aluminum oxide hydrate [9]. Its effectiveness for the adsorption of anatoxin, for example, clostridium anatoxin, has been proven. Oil adjuvants (emulsions) came into practice later than others. They are an antigen dissolved or suspended in water, which is dispersed in oil. As a result, the water droplets with the antigen are in the oil phase. This type of emulsion is called "water in oil". Highly purified liquid paraffin is used as an oil. In addition to the oil, an emulsifier must be present to stabilize the mixture. The positive effect of vaccination is achieved by the fact that the mineral oil is not metabolized, so that the drops of the emulsion with the antigen inside them are retained at the injection site for a long time. After the decomposition of the emulsion as a result of enzymatic cleavage of the emulsifier, the antigen is slowly released from these droplets. Oil adjuvants cause the development of a strong inflammatory reaction, which triggers the entire mechanism of the immune response.

Nanoparticles are one of the most modern adjuvants [4]. The nanoparticles associated with the antigen are purposefully absorbed by macrophages, which leads to an increased immune response [8, 14].

In our work, we decided not to deviate from the classical scheme of manufacturing an adjuvant. The components of the emulsion were selected based on the physico-chemical properties of the substances. The following compositions of complex oil adjuvants were obtained, presented in Table No. 1.

Conclusion

Based on the obtained results of technological research, the composition and technology of adjuvant compositions have been developed. The choice of excipients is justified. It was found that as auxiliary substances, the most optimal are TEA, lecithin, oleic acid, mannitol. Stable compositions were obtained using Total oils and base oil. The optimal conditions for the homogenization of the vaccine is a speed of 2800-3000 rpm, with a given time interval of 30-40 minutes. The stability of vaccine preparations with the use of oil adjuvant compositions has been studied. It was found that the most advantageous physical and technological properties for practical use were the vaccine samples with a volume ratio of antigen and adjuvant 40:60.

References

1. Aguilar J. C., Rodriguez E. G. Vaccine adjuvants revisited //Vaccine. – 2007. – Vol. 25. – No 19. - Р. 3752-3762.  DOI: 10.1016/j.vaccine.2007.01.111
2. Allison A. C., Byars N. E. Immunological adjuvants: desirable properties and side-effects //Molecular immunology. – 1991. – Vol. 28. – No 3. – Р. 279-284. https://doi.org/10.1016/0161-5890(91)90074-T
3. Byars N. E., Allison A. C. Immunologic adjuvants: general properties, advantages, and limitations //Laboratory methods in immunology. – 1990. – Р. 39-51.
4. Dufès C., Al Robaian M., Somani S. Transferrin and the transferrin receptor for the targeted delivery of therapeutic agents to the brain and cancer cells //Therapeutic delivery. – 2013. – Vol. 4. – No 5. – Р. 629-640. DOI: 10.4155/tde.13.21
5. Fooladi A.A.I., Sattari M., Nourani M. R. Synergistic effects between Staphylococcal enterotoxin type B and Monophosphoryl lipid A against mouse fibrosarcoma //Journal of BUON. – 2010. – Vol. 15. – No 2. – Р. 340-347.
6. Jennings R., Simms J. R., Heath A. W. Adjuvants and delivery systems for viral vaccines--mechanisms and potential //Developments in biological standardization. – 1998. – Vol. 92. – Р. 19-28.
7. Kanashkova T.A. et al. The specific immunoprophylaxis and immunotherapy of infectious diseases: ucheb. method . grant //Minsk : BSMU, 2009 . - 84. (in Russ.)
8. Kwak L. W., Longo D. L. Modern vaccine adjuvants //Cancer Chemotherapy and Biotherapy. – 1996. – Р. 749-763.
9. Mori A. et al. The vaccine adjuvant alum inhibits IL‐12 by promoting PI 3 kinase signaling while chitosan does not inhibit IL‐12 and enhances Th1 and Th17 responses //European journal of immunology. – 2012. – Vol. 42. – No 10. – Р. 2709-2719. DOI: 10.1002/eji.201242372
10. Niven R. Prospects and challenges: inhalation delivery systems //Therapeutic Delivery. – 2013. – Vol. 4. – No 5. – Р. 519-522. DOI: 10.4155/tde.13.18
11. Pat. 2432173 Russian Federation, MPK A61K39/095. Vaccines containing aluminum adjuvants and histidine / Contorno M., M. Maffei : the applicant and patentee Chiron SRL. - No 2007139924/15 ; appl. 29.10.2007, publ. 10.05.2009.
12. Singh M., O'Hagan D. T. Recent advances in vaccine adjuvants //Pharmaceutical research. – 2002. – Vol. 19. – No. 6. – Р. 715-728.
13. Tomljenovic L., Shaw C. A. Mechanisms of aluminum adjuvant toxicity and autoimmunity in pediatric populations //Lupus. – 2012. – Vol. 21. – No. 2. – Р. 223-230.   DOI: 10.1177/0961203311430221
14. Vogel F. R. Adjuvants in perspective //Developments in biological standardization. – 1998. – Vol. 92. – Р. 241-248.
15. Vogel F.R. et al. A summary compendium of vaccine adjuvants and excipients //Vaccine design: the subunit and adjuvant approach. — 1995, – No 5. — P. 234-250.

back