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

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.

Early treatment regimens achieve sustained virologic remission in infant macaques infected with SIV at birth.

Early antiretroviral therapy (ART) in HIV-infected infants generally fails to achieve a sustained state of ART-free virologic remission, even after years of treatment. Our studies show that viral reservoir seeding is different in neonatal macaques intravenously exposed to SIV at birth, in contrast to adults. Furthermore, one month of ART including an integrase inhibitor, initiated at day 3, but not day 4 or 5 post infection, efficiently and rapidly suppresses viremia to undetectable levels. Intervention initiated at day 3 post infection and continued for 9 months achieves a sustained virologic remission in 4 of 5 infants. Collectively, an early intervention strategy within a key timeframe and regimen may result in viral remission or successful post-exposure prophylaxis for neonatal SIV infection, which may be clinically relevant for optimizing treatment strategies for HIV-infected or exposed infants.