Are Hamsters a Suitable Model for Evaluating the Immunogenicity of RBD-Based Anti-COVID-19 Subunit Vaccines?

Merkuleva, Iuliia A.; Щербаков, Д. Н.; Borgoyakova, M. B.; Исаева, А. А.; Nesmeyanova, Valentina S.; Volkova, N. V.; Aripov, V. S.; Shanshin, Daniil V.; Karpenko, Larisa I.; Belenkaya, S. V.; Казачинская, Е. И.; Volosnikova, Ekaterina A.; Есина, Т. И.; Сергеев, А. А.; Titova, Kseniia A.; Konyakhina, Yulia V.; Zaykovskaya, А. V.; Pyankov, Oleg V.; Kolosova, E. A.; Viktorina, Olesya E.; Shelemba, A. A.; Рудометов, А. П.; Ilyichev, Alexander A.

doi:10.3390/v14051060

Cited by 13 publications

(12 citation statements)

References 45 publications

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“…Recombinant S protein or its parts (including RBD, S1, S2, trimerized RBD, full length spike ectodomain, etc.) have been evaluated as candidate vaccines in different animal models, at different concentrations, different schedules and formulated with different adjuvants (53)(54)(55)(56)(57)(58)(59)(60). Beyond experimental differences, in all cases the results obtained show that the different versions of S protein have immunostimulatory capacity to some degree.…”

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confidence: 99%

Immunological study of COVID-19 vaccine candidate based on recombinant spike trimer protein from different SARS-CoV-2 variants of concern

Rudi

Aispuro²,

Zurita³

et al. 2022

Front. Immunol.

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The emergency of new SARS-CoV-2 variants that feature increased immune escape marks an urgent demand for better vaccines that will provide broader immunogenicity. Here, we evaluated the immunogenic capacity of vaccine candidates based on the recombinant trimeric spike protein (S) of different SARS-CoV-2 variants of concern (VOC), including the ancestral Wuhan, Beta and Delta viruses. In particular, we assessed formulations containing either single or combined S protein variants. Our study shows that the formulation containing the single S protein from the ancestral Wuhan virus at a concentration of 2µg (SW2-Vac 2µg) displayed in the mouse model the highest IgG antibody levels against all the three (Wuhan, Beta, and Delta) SARS-CoV-2 S protein variants tested. In addition, this formulation induced significantly higher neutralizing antibody titers against the three viral variants when compared with authorized Gam-COVID-Vac-rAd26/rAd5 (Sputnik V) or ChAdOx1 (AstraZeneca) vaccines. SW2-Vac 2µg was also able to induce IFN-gamma and IL-17, memory CD4 populations and follicular T cells. Used as a booster dose for schedules performed with different authorized vaccines, SW2-Vac 2µg vaccine candidate also induced higher levels of total IgG and IgG isotypes against S protein from different SARS-CoV-2 variants in comparison with those observed with homologous 3-dose schedule of Sputnik V or AstraZeneca. Moreover, SW2-Vac 2µg booster induced broadly strong neutralizing antibody levels against the three tested SARS-CoV-2 variants. SW2-Vac 2µg booster also induced CD4+ central memory, CD4+ effector and CD8+ populations. Overall, the results demonstrate that SW2-Vac 2 µg is a promising formulation for the development of a next generation COVID-19 vaccine.

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confidence: 99%

Immunological study of COVID-19 vaccine candidate based on recombinant spike trimer protein from different SARS-CoV-2 variants of concern

Rudi

Aispuro²,

Zurita³

et al. 2022

Front. Immunol.

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“…These results are in partial disagreement with those by Merkuleva and colleagues who evaluated the immune response induced by a trimeric uncoupled RBD based candidate vaccine expressed in mammalian cells in different animal models. They showed a dose dependent virus VN antibody response in the hamster model, that however proved to be inferior to responses found in other animal models 39 . In our hands coupling of the SARS-CoV-2 RBD to a nanoparticle proved to be crucial for the induction of high titre VN antibodies and protection, as we have shown previously for a MERS-CoV candidate vaccine in different animal species 13 .…”

Section: Discussionmentioning

confidence: 68%

Preclinical immunogenicity and protective efficacy of a SARS-CoV-2 RBD based vaccine produced with the thermophilic filamentous fungal expression system Thermothelomyces heterothallica, C1.

Osterhaus

González-Hernández

Kaiser

et al. 2023

Preprint

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The emergency use of vaccines has been the most efficient way to control the ongoing COVID-19 pandemic. However, the emergence of SARS-CoV-2 variants of concern has reduced the efficacy of currently used vaccines. The receptor-binding domain (RBD) of the SARS-CoV-2 spike protein is the main target for virus neutralizing (VN) antibodies. Here, we evaluated the immunogenicity and efficacy of a SARS-CoV-2 RBD vaccine candidate produced in the Thermothelomyces heterothallica (formerly Myceliophthora thermophila), C1 protein expression system, in a Syrian golden hamster (Mesocricetus auratus) infection model. One dose of 10 µg RBD vaccine based on SARS-CoV-2 Wuhan strain, coupled to a nanoparticle in combination with aluminum hydroxide as adjuvant, efficiently induced VN antibodies and reduced viral load and lung damage upon SARS-CoV-2 challenge infection. The VN antibodies, neutralized SARS-CoV-2 variants of concern D614G, Alpha, Beta and Gamma. Our results support the use of the Thermothelomyces heterothallica, C1 protein expression system to produce recombinant vaccines against SARS-CoV-2 and other virus infections, in order to help overcome limitations associated with the use of mammalian expression systems.

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“…Using a similar AH-adjuvanted pre-fusion stabilized (S-2P) we found high neutralizing antibody responses 42 days after a single immunization in mice ( 34 ) and previous studies have demonstrated that the HexaPro antigen adjuvanted with AH elicits robust neutralizing antibody responses in mice when using a standard vaccine regimen (two doses given three weeks apart and evaluation of responses two weeks later) ( 49 ). In contrast, more recent studies have demonstrated that alum adjuvanted recombinant spike or RBD-based vaccines are poor at inducing neutralizing antibody responses, particularly in Syrian hamsters ( 50 , 51 ). In the present study, AH-adjuvanted spike protein was poor at inducing neutralizing antibody responses in Syrian hamsters, regardless of whether the vaccine was administered in an accelerated schedule (10 days apart) or a standard schedule (21 days apart).…”

Section: Discussionmentioning

confidence: 94%

SARS-CoV-2 spike HexaPro formulated in aluminium hydroxide and administered in an accelerated vaccination schedule partially protects Syrian Hamsters against viral challenge despite low neutralizing antibody responses

et al. 2023

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SARS-CoV-2 continues to pose a threat to human health as new variants emerge and thus a diverse vaccine pipeline is needed. We evaluated SARS-CoV-2 HexaPro spike protein formulated in Alhydrogel® (aluminium oxyhydroxide) in Syrian hamsters, using an accelerated two dose regimen (given 10 days apart) and a standard regimen (two doses given 21 days apart). Both regimens elicited spike- and RBD-specific IgG antibody responses of similar magnitude, but in vitro virus neutralization was low or undetectable. Despite this, the accelerated two dose regimen offered reduction in viral load and protected against lung pathology upon challenge with homologous SARS-CoV-2 virus (Wuhan-Hu-1). This highlights that vaccine-induced protection against SARS-CoV-2 disease can be obtained despite low neutralizing antibody levels and suggests that accelerated vaccine schedules may be used to confer rapid protection against SARS-CoV-2 disease.

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Are Hamsters a Suitable Model for Evaluating the Immunogenicity of RBD-Based Anti-COVID-19 Subunit Vaccines?

Cited by 13 publications

References 45 publications

Immunological study of COVID-19 vaccine candidate based on recombinant spike trimer protein from different SARS-CoV-2 variants of concern

Immunological study of COVID-19 vaccine candidate based on recombinant spike trimer protein from different SARS-CoV-2 variants of concern

Preclinical immunogenicity and protective efficacy of a SARS-CoV-2 RBD based vaccine produced with the thermophilic filamentous fungal expression system Thermothelomyces heterothallica, C1.

SARS-CoV-2 spike HexaPro formulated in aluminium hydroxide and administered in an accelerated vaccination schedule partially protects Syrian Hamsters against viral challenge despite low neutralizing antibody responses

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