Immune Responses Induced By SARS-CoV-2 Vaccination

Vaccination and infection are two different paths to immunity. Understanding adaptive immune responses to SARS-CoV-2 is important for vaccine development efforts, interpreting disease pathogenesis, and calibration of future pandemic control measures. 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 only detectable in 60-67% of subjects at 6 months. Lastly, subjects with pre-existing cross-reactive CD4+ T cell memory had increased CD4+ T cell and antibody responses to the vaccine, demonstrating the biological relevance of SARS-CoV-2–cross-reactive CD4+ T cells. This work expands our understanding of immune memory to mRNA vaccine in humans, the biological relevance of crossreactive T cells, and possible timing of boosters.

Daniela Weiskopf has devoted her career to understanding the T-cell response to viral pathogens and spent the last sixteen years studying infectious viruses relevant to human health and disease. In 2009, she received her PhD in Immunology from Innsbruck Medical University, Austria, where she performed research analyzing posttranslational modifications of virus-derived epitopes and modulation of the T cell immune response during aging. Following her Ph.D., she obtained post-doctoral training at the La Jolla Institute for Immunology (LJI) where her efforts were dedicated to characterizing human dengue virus-specific CD8+ and CD4+ T cell responses in samples from areas with endemic dengue infection and following experimental dengue vaccination. One important outcome of these studies was the development of dengue-specific epitope megapools (MPs) that allow the testing of virus-specific T cells in small amounts of blood irrespective of HLA restriction of the donor and infecting serotype. She hase further expanded my repertoire to study Zika and Chikungunya virus-specific T-cell responses. She has also become interested in the effects of pre-existing immunity against the dengue virus on subsequent zika virus infection. As a Research Assistant Professor in the Center for Infectious Diseases and Vaccine Research at LJI she has recently focused on the characterization of SARS-CoV-2 specific T cell responses. Understanding adaptive immune responses to SARS-CoV-2 is essential for vaccine development efforts, interpreting disease pathogenesis, and calibrating future pandemic control measures.