ABSTRACT
Multiple COVID-19 vaccines, representing diverse vaccine platforms, successfully protect against symptomatic COVID-19 cases and deaths. Head-to-head comparisons of T cell, B cell, and antibody responses to diverse vaccines in humans are likely to be informative for understanding protective immunity against COVID-19, with particular interest in immune memory. Here, SARS-CoV-2-spike--specific immune responses to Moderna mRNA-1273, Pfizer/BioNTech BNT162b2, Janssen Ad26.COV2.S and Novavax NVX-CoV2373 were examined longitudinally for 6 months. 100% of individuals made memory CD4+ T cells, with cTfh and CD4-CTL highly represented after mRNA or NVX-CoV2373 vaccination. mRNA vaccines and Ad26.COV2.S induced comparable CD8+ T cell frequencies, though memory CD8+ T cells were only detectable in 60-67% of subjects at 6 months. Ad26.COV2.S was not the strongest immunogen by any measurement, though the Ad26.COV2.S T cell, B cell, and antibody responses were relatively stable over 6 months. A differentiating feature of Ad26.COV2.S immunization was a high frequency of CXCR3+ memory B cells. mRNA vaccinees had substantial declines in neutralizing antibodies, while memory T cells and B cells were comparatively stable over 6 months. These results of these detailed immunological evaluations may also be relevant for vaccine design insights against other pathogens.
Subject(s)
Protein S Deficiency , Pulmonary Disease, Chronic Obstructive , COVID-19ABSTRACT
We address whether T cell responses induced by different vaccine platforms (mRNA-1273, BNT162b2, Ad26.COV2.S, NVX-CoV2373) cross-recognize SARS-CoV-2 variants. Preservation of at least 83% and 85% for CD4+ and CD8+ T cell responses was found, respectively, regardless of vaccine platform or variants analyzed. By contrast, highly significant decreases were observed for memory B cell and neutralizing antibody recognition of variants. Bioinformatic analyses showed full conservation of 91% and 94% of class II and class I spike epitopes. For Omicron, 72% of class II and 86% of class I epitopes were fully conserved, and 84% and 85% of CD4+ and CD8+ T cell responses were preserved. In-depth epitope repertoire analysis showed a median of 11 and 10 spike epitopes recognized by CD4+ and CD8+ T cells from vaccinees. Functional preservation of the majority of the T cell responses may play an important role as a second-level defense against diverse variants.