Heterologous versus homologous boosting regimens elicit qualitatively distinct, BA.5 cross reactive T cells in transplant recipients

Abstract The Omicron BA.5 subvariant of SARS-CoV-2 markedly escapes neutralizing antibodies induced by vaccination due to mutations in the Spike (S) protein. Solid organ transplant recipients (SOTRs) suffer high COVID-19 morbidity, yet show poor ancestral strain recognition after vaccination. CD8+ T cell responses may provide a crucial second line defense. Therefore, it is critical understand which vaccine regimens induce robust, conserved responses. We evaluated anti-S IgG titers, pseudo-neutralization, and S-specific CD4 CD8 SOTRs following homologous mRNA (mRNA-1273 or BNT16b2) heterologous Ad26.COV2.S (JNJ-78436735) boosting. Homologous boosting with three doses highest titers. However, both demonstrated significantly lower pseudo-neutralization against compared strain. In contrast, cells maintained cross-reactivity recognition. higher polyfunctional phenotypes associated metabolic immunologic activation. Comparing two platforms, mRNA-1273 IL-21+ peripheral follicular helper increased antibody titers BNT16b2. Heterologous did not increase boosting, as were low across all individuals. These data demonstrate that can cross-reactive emerging variants concern SOTRs, but currently available strategies do robust U01AI138897 U54CA260491