Carolyn Rydyznski Moderbacher

T cell, and antibody responses are protective, but uncoordinated responses frequently fail to control disease, with a connection between aging and impaired adaptive immune responses to SARS-CoV-2.

A smaller-dose jab does the job Low-dose messenger RNA (mRNA) vaccines potentially allow health providers to administer more doses from a limited vaccine supply and can be less reactogenic. Whether low-dose COVID-19 mRNA vaccines generate immune responses comparable to currently approved doses remains an open question, however. Mateus et al . report the results of a clinical trial comparing patients who received a 25-μg mRNA-1273 (Moderna) COVID-19 vaccine to 100-μg mRNA-1273 COVID-19 vaccinees and severe acute respiratory syndrome coronavirus 2–infected individuals. The low-dose Moderna vaccine generated long-lived T cell immunity that was equivalent between younger and older patients and that could be enhanced by the presence of cross-reactive T cells. Moreover, antibody and T cell responses induced by the low-dose vaccine were comparable to natural infection and about half as strong as those seen with high-dose vaccination. —STS

SUMMARY 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.