Immunogenicity and efficacy of vaccine boosters against SARS-CoV-2 Omicron subvariant BA.5 in male Syrian hamsters

Abstract

The SARS-CoV-2 Omicron subvariant BA.5 rapidly spread worldwide and replaced BA.1/BA.2 in many countries, becoming globally dominant. BA.5 has unique amino acid substitutions in the spike protein that both mediate immune escape from neutralizing antibodies produced by immunizations and increase ACE2 receptor binding affinity. In a comprehensive, long-term (up to 9 months post primary vaccination), experimental vaccination study using male Syrian hamsters, we evaluate neutralizing antibody responses and efficacy against BA.5 challenge after primary vaccination with Ad26.COV2.S (Janssen) or BNT162b2 (Pfizer/BioNTech) followed by a homologous or heterologous booster with mRNA-1273 (Moderna) or NVX-CoV2373 (Novavax). Notably, one high or low dose of Ad26.COV2.S provides more durable immunity than two primary doses of BNT162b2, and the NVX-CoV2373 booster provides the strongest augmentation of immunity, reduction in BA.5 viral replication, and disease. Our data demonstrate the immunogenicity and efficacy of different prime/boost vaccine regimens against BA.5 infection in an immune-competent model and provide new insights regarding COVID-19 vaccine strategies.

Antigen-display exosomes provide adjuvant-free protection against SARS-CoV-2 disease at nanogram levels of spike protein

“…Furthermore, we show that injection of spike-EMAD13 exosomes elicited protective immunity against SARS-CoV-2 disease at doses of just 0.5-5 ng of spike protein, without adjuvant. Given that the FDA-approved recombinant spike protein vaccine, NVX-CoV2373, is dosed at 5-25 μg of spike protein and requires co-injection with an inflammatory adjuvant( 20, 21 ), our results support the hypothesis that exosome display technologies increase antigen immunogenicity significantly. Given our ability to genetically program antigens onto the exosomes surface, and work by others showing that exosomes can be lyophilized without dramatically altering their stability( 22, 23 ), exosome display technology has potential applications to both expression-dependent and structural vaccines.…”

“…Immunized animals also had significant virus neutralizing activity, which in high-dose animals was comparable to that of subjects immunized with FDA-approved spike mRNA vaccines( 51 ). Notably, these protective immune responses were induced by just 0.5-5 ng of exosome-displayed spike protein, without adjuvant, whereas the FDA-approved recombinant spike protein vaccine is dosed in hamsters at 1000-fold higher amounts of spike protein, 5 μg, and together with an inflammatory adjuvant( 21 ).…”

Immunogenicity and safety of a live-attenuated SARS-CoV-2 vaccine candidate based on multiple attenuation mechanisms

“…For example, a reduction in neutralizing antibodies was observed in humans after six months (Zhang et al, 2022). In hamsters, these were undetectable after 250 days (Machado et al, 2023). Therefore, we evaluated the persistence of the immune response induced by BK2102 using a hamster model.…”

Analysis of the protective efficacy of approved COVID-19 vaccines against Omicron variants and the prospects for universal vaccines

“…The ancestral amino acids at 69-70del, L452R, F486V, and position Q493 differ from BA.2 ( 81 ). The spike protein of BA.5 contains a unique amino acid substitution, which not only facilitates the evasion of nAbs produced by vaccination but also enhances its binding affinity to the ACE2 receptor ( 82 ).…”

“…Compared with that of D614G, the ID50 titer of BA.4/5 decreased 12-fold (7687 vs. 628) after three doses of the original COVID-19 mRNA vaccine ( 25 ). The study observed that the 50% plaque reduction neutralization test (PRNT50) titer in male serum was 1.61 times higher than that of BA.1 (1686 vs. 1049) after two doses of mRNA vaccine and one dose of BNT162b2 vaccine ( 82 ). Neutralization assays were conducted on plasma samples obtained from the inoculated individuals at 1–5 months after receiving three doses of an mRNA vaccine (BNT162b2 or mRNA-1273).…”