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Potent neutralization of SARS-CoV-2 including variants of concern by vaccines presenting the receptor-binding domain multivalently from nanoscaffolds.

ABSTRACT: The persistence of the global severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has brought to the forefront the need for safe and effective vaccination strategies. In particular, the emergence of several variants with greater infectivity and resistance to current vaccines has motivated the development of a vaccine that elicits a broadly neutralizing immune response against all variants. In this study, we used a nanoparticle-based vaccine platform for the multivalent display of the receptor-binding domain (RBD) of the SARS-CoV-2 spike (S) protein, the primary target of neutralizing antibodies. Multiple copies of RBD were conjugated to the SpyCatcher-mi3 protein nanoparticle to produce a highly immunogenic nanoparticle-based vaccine. RBD-SpyCatcher-mi3 vaccines elicited broadly cross-reactive antibodies that recognized the spike proteins of not just an early isolate of SARS-CoV-2, but also three SARS-CoV-2 variants of concern as well as SARS-CoV-1. Moreover, immunization elicited high neutralizing antibody titers against an early isolate of SARS-CoV-2 as well as four variants of concern, including the delta variant. These results reveal the potential of RBD-SpyCatcher-mi3 as a broadly protective vaccination strategy.

SUBMITTER: Halfmann PJ

PROVIDER: S-EPMC8459632 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:The SARS-CoV-2 pandemic has, as of July 2022, infected more than 550 million people and caused over 6 million deaths across the world. COVID-19 vaccines were quickly developed to protect against severe disease, hospitalization and death. In the present study, we performed a direct comparative analysis of four COVID-19 vaccines: BNT162b2 (Pfizer/BioNTech), mRNA-1273 (Moderna), ChAdOx1 (Oxford/AstraZeneca) and Ad26.COV2.S (Johnson & Johnson/Janssen), following primary and booster vaccination. We focused on the vaccine-induced antibody-mediated immune response against multiple SARS-CoV-2 variants: wildtype, B.1.1.7 (Alpha), B.1.351 (Beta), B.1.617.2 (Delta) and B.1.1.529 (Omicron). The analysis included the quantification of total IgG levels against SARS-CoV-2 Spike, as well as the quantification of antibody neutralization titers. Furthermore, the study assessed the high-throughput ACE2 competition assay as a surrogate for the traditional pseudovirus neutralization assay. The results demonstrated marked differences in antibody-mediated immune responses. The lowest Spike-specific IgG levels and antibody neutralization titers were induced by one dose of the Ad26.COV2.S vaccine, intermediate levels by two doses of the BNT162b2 vaccine, and the highest levels by two doses of the mRNA-1273 vaccine or heterologous vaccination of one dose of the ChAdOx1 vaccine and a subsequent mRNA vaccine. The study also demonstrated that accumulation of SARS-CoV-2 Spike protein mutations was accompanied by a marked decline in antibody neutralization capacity, especially for B.1.1.529. Administration of a booster dose was shown to significantly increase Spike-specific IgG levels and antibody neutralization titers, erasing the differences between the vaccine-induced antibody-mediated immune response between the four vaccines. The findings of this study highlight the importance of booster vaccines and the potential inclusion of future heterologous vaccination strategies for broad protection against current and emerging SARS-CoV-2 variants.

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Potent neutralization of SARS-CoV-2 including variants of concern by vaccines presenting the receptor-binding domain multivalently from nanoscaffolds.

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