Abstract

Emerging SARS-CoV-2 variants with the potential to escape binding and neutralizing antibody responses pose a threat to vaccine efficacy. We recently reported expansion of broadly neutralizing activity of vaccine-elicited antibodies in humans 8 months following a single immunization with Ad26.COV2.S. Here, we assessed the 15-month durability of antibody responses and their neutralizing capacity to B.1.617.2 (delta) and B.1.351 (beta) variants following a single immunization of Ad26.COV2.S in mice. We report the persistence of binding and neutralizing antibody titers following immunization with a concomitant increase in neutralizing antibody breadth to delta and beta variants over time. Evaluation of bone marrow and spleen at 15 months postimmunization revealed that Ad26.COV2.S-immunized mice tissues contained spike-specific antibody-secreting cells. We conclude that immunization with Ad26.COV2.S elicits a robust immune response against SARS-CoV-2 spike, which expands over time to neutralize delta and beta variants more robustly, and seeds bone marrow and spleen with long-lived spike-specific antibody-secreting cells. These data extend previous findings in humans and support the use of a mouse model as a potential tool to further explore the dynamics of the humoral immune response following vaccination with Ad26.COV2.S.

Highlights

  • Several vaccines have been developed against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)[1,2,3,4], the virus responsible for the coronavirus disease 2019 (COVID-19) pandemic[5,6]

  • To compare the immunogenicity of two candidate adenovirus serotype 26 (Ad26) vaccines expressing modified versions of the SARS-CoV-2 full-length spike (S) protein, groups of female wild-type BALB/c mice were immunized with a single dose of 1 × (N = 5), 1 × (N = 5), or 1 × (N = 10) viral particles Ad26.COV2.S or Ad26.S.dTM.PP via the intramuscular (IM) route

  • Evaluation of binding antibody titers by enzyme-linked immunosorbent assay (ELISA) showed induction of WA1/2020 S-specific titers in mice immunized with Ad26.S.dTM.PP, though responses appeared

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Summary

Introduction

Several vaccines have been developed against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)[1,2,3,4], the virus responsible for the coronavirus disease 2019 (COVID-19) pandemic[5,6]. We explored the kinetics of binding antibody responses to emerging SARS-CoV-2 variants of concern in the mice immunized npj Vaccines (2022) 23

Results
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