NVX-CoV2373 vaccination induces functional SARS-CoV-2-specific CD4+ and CD8+ T cell responses (preprint)

NVX-CoV2373 is an adjuvanted recombinant full-length SARS-CoV-2 spike trimer protein vaccine demonstrated to be protective against COVID-19 in efficacy trials. Here we demonstrate that vaccinated subjects made CD4+ T cell responses after one and two doses of NVX-CoV2373, and a subset of individuals made CD8+ T cell responses. Characterization of the vaccine-elicited CD8+ T cells demonstrated IFN{gamma} production. Characterization of the vaccine-elicited CD4+ T cells revealed both circulating T follicular helper cells (cTFH) and TH1 cells (IFN{gamma}, TNF, and IL-2) were detectable within 7 days of the primary immunization. Spike-specific CD4+ T cells were correlated with the magnitude of the later SARS-CoV-2 neutralizing antibody titers, indicating that robust generation of CD4+ T cells, capable of supporting humoral immune responses, may be a key characteristic of NVX-CoV2373 which utilizes Matrix-M adjuvant.

Humoral and cellular immune memory to four COVID-19 vaccines (preprint)

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.

Low dose mRNA-1273 COVID-19 vaccine generates durable T cell memory and antibodies enhanced by pre-existing crossreactive T cell memory (preprint)

Understanding human immune responses to SARS-CoV-2 RNA vaccines is of interest for a panoply of reasons. Here we examined vaccine-specific CD4+ T cell, CD8+ T cell, binding antibody, and neutralizing antibody responses to the 25 ug Moderna mRNA-1273 vaccine over 7 months post-immunization, including multiple age groups, with a particular interest in assessing whether pre-existing crossreactive T cell memory impacts vaccine-generated immunity. Low dose (25 ug) mRNA-1273 elicited durable Spike binding antibodies comparable to that of convalescent COVID-19 cases. Vaccine-generated Spike memory CD4+ T cells 6 months post-boost were comparable in quantity and quality to COVID-19 cases, including the presence of TFH cells and IFNg-expressing cells. Spike CD8+ T cells were generated in 88% of subjects, with equivalent percentages of CD8+ T cell memory responders at 6 months post-boost compared to COVID-19 cases. Lastly, subjects with pre-existing crossreactive CD4+ T cell memory had increased CD4+ T cell and antibody responses to the vaccine, demonstrating a biological relevance of SARS-CoV-2 crossreactive CD4+ T cells.