Neutralizing antibody response to SARS-CoV-2 bivalent mRNA vaccine in SIV-infected rhesus macaques: Enhanced immunity to XBB subvariants by two-dose vaccination

J Med Virol. 2024 Mar;96(3):e29520. doi: 10.1002/jmv.29520.

Abstract

The evolution of SARS-CoV-2 paired with immune imprinting by prototype messenger RNA (mRNA) vaccine has challenged the current vaccination efficacy against newly emerged Omicron subvariants. In our study, we investigated a cohort of macaques infected by SIV and vaccinated with two doses of bivalent Pfizer mRNA vaccine containing wildtype and BA.5 spikes. Using a pseudotyped lentivirus neutralization assay, we determined neutralizing antibody (nAb) titers against new XBB variants, i.e., XBB.1.5, XBB.1.16, and XBB.2.3, alongside D614G and BA.4/5. We found that compared to humans vaccinated with three doses of monovalent mRNA vaccine plus a bivalent booster, the monkeys vaccinated with two doses of bivalent mRNA vaccines exhibited relatively increased titers against XBB subvariants. Of note, SIV-positive dam macaques had reduced nAb titers relative to SIV-negative dams. Additionally, SIV positive dams that received antiretroviral therapy had lower nAb titers than untreated dams. Our study underscores the importance of reformulating the COVID-19 vaccine to better protect against newly emerged XBB subvariants as well as the need for further investigation of vaccine efficacy in individuals living with HIV-1.

Keywords: SARS‐CoV‐2; SIV; mRNA vaccination; neutralizing antibody; rhesus macaque.

MeSH terms

  • Animals
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • COVID-19 Vaccines
  • COVID-19* / prevention & control
  • Humans
  • Macaca mulatta
  • RNA, Messenger
  • SARS-CoV-2 / genetics
  • Vaccination
  • Vaccines, Combined
  • mRNA Vaccines*

Substances

  • Vaccines, Combined
  • mRNA Vaccines
  • COVID-19 Vaccines
  • Antibodies, Neutralizing
  • RNA, Messenger
  • Antibodies, Viral