Abstract
The ongoing coronavirus disease 2019 (COVID-19) pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Most of the currently approved SARS-CoV-2 vaccines use the prototype strain-derived spike (S) protein or its receptor-binding domain (RBD) as the vaccine antigen. The emergence of several novel SARS-CoV-2 variants has raised concerns about potential immune escape. In this study, we performed an immunogenicity comparison of prototype strain-derived RBD, S1, and S ectodomain trimer (S-trimer) antigens and evaluated their induction of neutralizing antibodies against three circulating SARS-CoV-2 variants, including B.1.1.7, B.1.351, and B.1.617.1. We found that, at the same antigen dose, the RBD and S-trimer vaccines were more potent than the S1 vaccine in eliciting long-lasting, high-titer broadly neutralizing antibodies in mice. The RBD immune sera remained highly effective against the B.1.1.7, B.1.351, and B.1.617.1 variants despite the corresponding neutralizing titers decreasing by 1.2-, 2.8-, and 3.5-fold relative to that against the wild-type strain. Significantly, the S-trimer immune sera exhibited comparable neutralization potency (less than twofold variation in neutralizing GMTs) towards the prototype strain and all three variants tested. These findings provide valuable information for further development of recombinant protein-based SARS-CoV-2 vaccines and support the continued use of currently approved SARS-CoV-2 vaccines in the regions/countries where variant viruses circulate.
Highlights
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the ongoing coronavirus disease 2019 (COVID-19) pandemic [1,2,3]
The S1 subunit can be further divided into the N-terminal domain (NTD) and the C-terminal domain (CTD); the latter can directly bind to the host cell receptor angiotensin-converting enzyme 2 (ACE2) and is referred to as the receptor-binding domain (RBD) [4,5]
The identity of the three recombinant proteins was confirmed by SDS-PAGE and western blot analyses (Figure 1A)
Summary
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the ongoing coronavirus disease 2019 (COVID-19) pandemic [1,2,3]. Several SARS-CoV-2 variants of concern have emerged and are circulating worldwide, including the B.1.1.7 lineage first identified in the United Kingdom, the B.1.351 lineage in South Africa, and the P.1 lineage in Brazil. These variants, especially B.1.351, contain multiple mutations in the S protein and show increased resistance to neutralization by some potent monoclonal antibodies, convalescent plasma, and vaccinee sera [6,7], threatening the protective efficacy of currently approved vaccines that were developed based on the original SARS-CoV-2 virus from initial outbreaks. In an attempt to assess the recombinant protein vaccines developed based on the SARS-CoV-2 prototype strain (Wuhan-Hu-1), three recombinant proteins, namely, RBD, S1, and S ectodomain trimer (S-trimer), were produced in mammalian cells and subsequently analyzed for their immunogenicity and ability to induce cross-neutralizing antibodies against SARS-CoV-2 variants
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