Omicron variant BA.1, BA.5, BQ.1.1, and XBB.1.5 Neutralizing Antibodies Following BNT162b2 BA.4/5 versus mRNA-1273 BA.1 Bivalent Vaccination (preprint)

Neutralization of Omicron subvariants by different bivalent vaccines have not been well evaluated. This study characterized neutralization against Omicron subvariants in 98 individuals receiving dialysis or with a kidney transplant receiving the BNT162b2 (BA.4/BA.5) or mRNA-1273 (BA.1) bivalent COVID-19 vaccine. Neutralization against Omicron BA.1, BA.5, BQ.1.1, and XBB.1.5 increased by 8-fold one month following bivalent vaccination. In comparison to wild-type (D614G), neutralizing antibodies against Omicron-specific variants were 7.3-fold lower against BA.1, 8.3-fold lower against BA.5, 45.8-fold lower against BQ.1.1, and 48.2-fold lower against XBB.1.5. Viral neutralization was not significantly different by bivalent vaccine type for wild-type (D614G) (P=0.48), BA.1 (P=0.21), BA.5 (P=0.07), BQ.1.1 (P=0.10), nor XBB.1.5 (P=0.10). Hybrid immunity conferred higher neutralizing antibodies against all Omicron subvariants. Given that both BNT162b2 (BA.4/BA.5) and mRNA-1273 (BA.1) induced similar neutralization against all Omicron subvariants, this suggests that bivalent vaccines confer protection even when they are antigenically divergent from the circulating variant.

Longitudinal Assessment of SARS-CoV-2 Specific T Cell Cytokine-Producing Responses for 1 Year Reveals Persistence of Multi-Cytokine Proliferative Responses, with Greater Immunity Associated with Disease Severity (preprint)

Cellular-mediated immunity is critical for long-term protection against most viral infections, including coronaviruses. We studied 23 SARS-CoV-2-infected survivors over a one year post symptom onset (PSO) interval by ex vivo cytokine ELISpot assay. All subjects demonstrated SARS-CoV-2-specific IFN-{gamma}, IL-2, and Granzyme B (GzmB) T cell responses at presentation, with greater frequencies in severe disease. Cytokines, mainly produced by CD4+ T cells, targeted all structural proteins (Nucleocapsid, Membrane, Spike) except Envelope, with GzmB > IL-2 > IFN-{gamma}. Mathematical modeling predicted that: 1) cytokine responses peaked at 6 days for IFN-{gamma}, 36 days for IL-2, and 7 days for GzmB, 2) severe illness was associated with reduced IFN-{gamma} and GzmB, but increased IL-2 production rates, 3) males displayed greater production of IFN-{gamma}, whereas females produced more GzmB. Ex vivo responses declined over time with persistence of IL-2 in 86% and of IFN-{gamma} and GzmB in 70% of subjects at a median of 336 days PSO. The average half-life of SARS-CoV-2-specific cytokine-producing cells was modelled to be 139 days (~4.6 months). Potent T cell proliferative responses persisted throughout observation, were CD4 dominant, and were capable of producing all 3 cytokines. Several immunodominant CD4 and CD8 epitopes identified in this study were shared by seasonal coronaviruses or SARS-CoV-1 in the Nucleocapsid and Membrane regions. Both SARS-CoV-2-specific CD4+ and CD8+ T cell clones were able to kill target cells, though CD8 tended to be more potent.