Development of a vaccine adjuvant based on squalene and study of its adjuvant properties

The use of modern subunit vaccines involves adjuvant introduction into their composition. Currently, the search for new and improvement of existing adjuvant systems is actively underway. Squalene- based adjuvants are well-known and approved in a number of countries for clinical use in influenza vacc...

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Main Authors: E. A. Volosnikova, D. N. Shcherbakov, V. V. Ermolaev, N. V. Volkova, O. N. Kaplina, M. B. Borgoyakova, E. D. Danilenko
Format: Article
Language:Russian
Published: St. Petersburg branch of the Russian Association of Allergologists and Clinical Immunologists 2023-06-01
Series:Медицинская иммунология
Subjects:
Online Access:https://www.mimmun.ru/mimmun/article/view/2824
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author E. A. Volosnikova
D. N. Shcherbakov
V. V. Ermolaev
N. V. Volkova
O. N. Kaplina
M. B. Borgoyakova
E. D. Danilenko
author_facet E. A. Volosnikova
D. N. Shcherbakov
V. V. Ermolaev
N. V. Volkova
O. N. Kaplina
M. B. Borgoyakova
E. D. Danilenko
author_sort E. A. Volosnikova
collection DOAJ
description The use of modern subunit vaccines involves adjuvant introduction into their composition. Currently, the search for new and improvement of existing adjuvant systems is actively underway. Squalene- based adjuvants are well-known and approved in a number of countries for clinical use in influenza vaccines. Our study was devoted to the development of an adjuvant composition on the basis of squalene. The resulting adjuvants were composed in a form of oil emulsion containing a hydrophilic and hydrophobic phase. The stability of the emulsion was achieved by treating it with ultrasound at a frequency of 22 kHz. Particle sizes of the obtained emulsions were examined with the use of an electron microscope. The particle size was calculated to be 50-80 nm for the majority of particles (84%). Adjuvant activity was evaluated in 100 male Balb/C mice, weighing 16-18 g. To assess the humoral immune response, immunization was performed twice, with a 14-day interval, by intramuscular injection of 200 mL per animal. The receptor-binding domain (RBD) of the surface S protein of the severe acute respiratory syndrome coronavirus 2 (Delta variant (B.1.617.2)) or ovalbumin (OVA) from chicken eggs were used as antigens. RBD was administered at a dose of 50 mg/animal; OVA was administered at two doses (1 mg or 5 mg/animal). An antigen with aluminum hydroxide was used as a positive control; a saline solution was used as a negative control. The effectiveness of the obtained adjuvants was determined by measuring the titers of specific antibodies in mouse sera in ELISA assays using the recombinant RBD of SARS-CoV-2 S-protein or ovalbumin from chicken eggs. It was shown that the use of squalene-based adjuvants increased the antigens’ immunogenicity. The average titers of specific antibodies against RBD in the experimental group were 4 times higher than in the group immunized with RBD adjuvanted with aluminum hydroxide. An increase in immunogenicity of the antigen adjuvanted with squalene was also observed in the experimental OVA-group. Thus, it was shown that the developed squalene-based adjuvant compositions could be an alternative to the traditional adjuvants based on aluminum salts.
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spelling doaj.art-6cb8669b05484e6081721e4708336eec2024-04-22T13:07:49ZrusSt. Petersburg branch of the Russian Association of Allergologists and Clinical ImmunologistsМедицинская иммунология1563-06252313-741X2023-06-0125368569010.15789/1563-0625-DOA-28241659Development of a vaccine adjuvant based on squalene and study of its adjuvant propertiesE. A. Volosnikova0D. N. Shcherbakov1V. V. Ermolaev2N. V. Volkova3O. N. Kaplina4M. B. Borgoyakova5E. D. Danilenko6State Research Center of Virology and Biotechnology “Vector”State Research Center of Virology and Biotechnology “Vector”State Research Center of Virology and Biotechnology “Vector”State Research Center of Virology and Biotechnology “Vector”State Research Center of Virology and Biotechnology “Vector”State Research Center of Virology and Biotechnology “Vector”State Research Center of Virology and Biotechnology “Vector”The use of modern subunit vaccines involves adjuvant introduction into their composition. Currently, the search for new and improvement of existing adjuvant systems is actively underway. Squalene- based adjuvants are well-known and approved in a number of countries for clinical use in influenza vaccines. Our study was devoted to the development of an adjuvant composition on the basis of squalene. The resulting adjuvants were composed in a form of oil emulsion containing a hydrophilic and hydrophobic phase. The stability of the emulsion was achieved by treating it with ultrasound at a frequency of 22 kHz. Particle sizes of the obtained emulsions were examined with the use of an electron microscope. The particle size was calculated to be 50-80 nm for the majority of particles (84%). Adjuvant activity was evaluated in 100 male Balb/C mice, weighing 16-18 g. To assess the humoral immune response, immunization was performed twice, with a 14-day interval, by intramuscular injection of 200 mL per animal. The receptor-binding domain (RBD) of the surface S protein of the severe acute respiratory syndrome coronavirus 2 (Delta variant (B.1.617.2)) or ovalbumin (OVA) from chicken eggs were used as antigens. RBD was administered at a dose of 50 mg/animal; OVA was administered at two doses (1 mg or 5 mg/animal). An antigen with aluminum hydroxide was used as a positive control; a saline solution was used as a negative control. The effectiveness of the obtained adjuvants was determined by measuring the titers of specific antibodies in mouse sera in ELISA assays using the recombinant RBD of SARS-CoV-2 S-protein or ovalbumin from chicken eggs. It was shown that the use of squalene-based adjuvants increased the antigens’ immunogenicity. The average titers of specific antibodies against RBD in the experimental group were 4 times higher than in the group immunized with RBD adjuvanted with aluminum hydroxide. An increase in immunogenicity of the antigen adjuvanted with squalene was also observed in the experimental OVA-group. Thus, it was shown that the developed squalene-based adjuvant compositions could be an alternative to the traditional adjuvants based on aluminum salts.https://www.mimmun.ru/mimmun/article/view/2824adjuvantsqualeneimmune responses proteinovalbuminimmunization
spellingShingle E. A. Volosnikova
D. N. Shcherbakov
V. V. Ermolaev
N. V. Volkova
O. N. Kaplina
M. B. Borgoyakova
E. D. Danilenko
Development of a vaccine adjuvant based on squalene and study of its adjuvant properties
Медицинская иммунология
adjuvant
squalene
immune response
s protein
ovalbumin
immunization
title Development of a vaccine adjuvant based on squalene and study of its adjuvant properties
title_full Development of a vaccine adjuvant based on squalene and study of its adjuvant properties
title_fullStr Development of a vaccine adjuvant based on squalene and study of its adjuvant properties
title_full_unstemmed Development of a vaccine adjuvant based on squalene and study of its adjuvant properties
title_short Development of a vaccine adjuvant based on squalene and study of its adjuvant properties
title_sort development of a vaccine adjuvant based on squalene and study of its adjuvant properties
topic adjuvant
squalene
immune response
s protein
ovalbumin
immunization
url https://www.mimmun.ru/mimmun/article/view/2824
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AT nvvolkova developmentofavaccineadjuvantbasedonsqualeneandstudyofitsadjuvantproperties
AT onkaplina developmentofavaccineadjuvantbasedonsqualeneandstudyofitsadjuvantproperties
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