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Hamsters Protected from SARS-CoV-2 Delta Variant Challenge after Two Doses of Adjuvanted SARS-CoV-2 Recombinant Spike Protein (S-2P) and One Dose of Beta S-2P.

ABSTRACT: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern negatively impact the effectiveness of vaccines. In this study, we challenge hamsters with the delta variant after 2- or 3-dose inoculations with SARS-CoV-2 vaccines constructed from stabilized prefusion spike proteins (S-2P) of Wuhan (W) and beta (B) variants. Compared to 3 doses of W S-2P, 2 doses of W S-2P followed by a third dose of B S-2P induced the highest neutralizing antibody titer against live SARS-CoV-2 virus and enhanced neutralization of omicron variant pseudovirus. Reduced lung live virus titer and pathology suggested that all vaccination regimens protect hamsters from SARS-CoV-2 delta variant challenge.

SUBMITTER: Kuo TY

PROVIDER: S-EPMC9047188 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

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Hamsters Protected from SARS-CoV-2 Delta Variant Challenge after Two Doses of Adjuvanted SARS-CoV-2 Recombinant Spike Protein (S-2P) and One Dose of Beta S-2P.

Kuo Tsun-Yung TY Lien Chia En CE Lin Yi-Jiun YJ Lin Meei-Yun MY Wu Chung-Chin CC Tang Wei-Hsuan WH Campbell John D JD Traquina Paula P Chuang Ya-Shan YS Liu Luke Tzu-Chi LT Cheng Jinyi J Chen Charles C

The Journal of infectious diseases 20221101 9

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern negatively impact the effectiveness of vaccines. In this study, we challenge hamsters with the delta variant after 2- or 3-dose inoculations with SARS-CoV-2 vaccines constructed from stabilized prefusion spike proteins (S-2P) of Wuhan (W) and beta (B) variants. Compared to 3 doses of W S-2P, 2 doses of W S-2P followed by a third dose of B S-2P induced the highest neutralizing antibody titer against live SARS-CoV-2 v ...[more]

PMID: 35451470

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Project description:The ongoing evolution of SARS-CoV-2 variants emphasizes the need for vaccines providing broad cross-protective immunity. This study was undertaken to assess the ability of Advax-CpG55.2 adjuvanted monovalent recombinant spike protein (Wuhan, Beta, Gamma) vaccines or a trivalent formulation to protect hamsters againstBeta or Delta virus infection. The ability of vaccines to block virus transmission to naïve co-housed animals was also assessed. In naïve hosts, the Beta variant induced higher virus loads than the Delta variant, and conversely the Delta variant caused more severe disease and was more likely to be associated with virus transmission. The trivalent vaccine formulation provided the best protection against both Beta and Delta infection and also completely prevented virus transmission. The next best performing vaccine was the original monovalent Wuhan-based vaccine. Notably, hamsters that received the monovalent Gamma spike vaccine had the highest viral loads and clinical disease of all the vaccine groups, a potential signal of antibody dependent-enhancement (ADE). These hamsters were also the most likely to transmit Delta virus to naïve recipients. In murine studies, the Gamma spike vaccine induced the highest total spike protein to RBD IgG ratio and the lowest levels of neutralizing antibody, a context that could predispose to ADE. Overall, the study results confirmed that the current SpikoGen® vaccine based on Wuhan spike protein was still able to protect against clinical disease caused by either the Beta or Delta virus variants but suggested additional protection may be obtained by combining it with extra variant spike proteins to make a multivalent formulation. This study highlights the complexity of optimizing vaccine protection against multiple SARS-CoV-2 variants and stresses the need to continue to pursue new and improved COVID-19 vaccines able to provide robust, long-lasting, and broadly cross-protective immunity against constantly evolving SARS-CoV-2 variants.

Project description:As the COVID-19 pandemic transitions into endemicity, seasonal boosters are a plausible reality across the globe. We hypothesize that intranasal vaccines can provide better protection against asymptomatic infections and more transmissible variants of SARS-CoV-2. To formulate a protective intranasal vaccine, we utilized a VLP-based platform. Hepatitis B surface antigen-based virus like particles (VLP) linked with receptor binding domain (RBD) antigen were paired with the TLR4-based agonist adjuvant, BECC 470. K18-hACE2 mice were primed and boosted at four-week intervals with either VLP-RBD-BECC or mRNA-1273. Both VLP-RBD-BECC and mRNA-1273 vaccination resulted in production of RBD-specific IgA antibodies in serum. RBD-specific IgA was also detected in the nasal wash and lung supernatants and were highest in VLP-RBD-BECC vaccinated mice. Interestingly, VLP-RBD-BECC vaccinated mice showed slightly lower levels of pre-challenge IgG responses, decreased RBD-ACE2 binding inhibition, and lower neutralizing activity in vitro than mRNA-1273 vaccinated mice. Both VLP-RBD-BECC and mRNA-1273 vaccinated mice were protected against challenge with a lethal dose of Delta variant SARS-CoV-2. Both vaccines limited viral replication and viral RNA burden in the lungs of mice. CXCL10 is a biomarker of severe SARS-CoV-2 infection and we observed both vaccines limited expression of serum and lung CXCL10. Strikingly, VLP-RBD-BECC when administered intranasally, limited lung inflammation at early timepoints that mRNA-1273 vaccination did not. VLP-RBD-BECC immunization elicited antibodies that do recognize SARS-CoV-2 Omicron variant. However, VLP-RBD-BECC immunized mice were protected from Omicron challenge with low viral burden. Conversely, mRNA-1273 immunized mice had low to no detectable virus in the lungs at day 2. Together, these data suggest that VLP-based vaccines paired with BECC adjuvant can be used to induce protective mucosal and systemic responses against SARS-CoV-2.

Dataset Information

Hamsters Protected from SARS-CoV-2 Delta Variant Challenge after Two Doses of Adjuvanted SARS-CoV-2 Recombinant Spike Protein (S-2P) and One Dose of Beta S-2P.

Publications

Hamsters Protected from SARS-CoV-2 Delta Variant Challenge after Two Doses of Adjuvanted SARS-CoV-2 Recombinant Spike Protein (S-2P) and One Dose of Beta S-2P.

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