@article {Zhang2022.03.18.484953, author = {Zeli Zhang and Jose Mateus and Camila H. Coelho and Jennifer M. Dan and Carolyn Rydyznski Moderbacher and Rosa Isela G{\'a}lvez and Fernanda H. Cortes and Alba Grifoni and Alison Tarke and James Chang and E. Alexandar Escarrega and Christina Kim and Benjamin Goodwin and Nathaniel I. Bloom and April Frazier and Daniela Weiskopf and Alessandro Sette and Shane Crotty}, title = {Humoral and cellular immune memory to four COVID-19 vaccines}, elocation-id = {2022.03.18.484953}, year = {2022}, doi = {10.1101/2022.03.18.484953}, publisher = {Cold Spring Harbor Laboratory}, 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{\textemdash}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.Competing Interest StatementA.S. is a consultant for Gritstone Bio, Flow Pharma, ImmunoScape, Avalia, Moderna, Fortress, Repertoire, Gerson Lehrman Group, RiverVest, MedaCorp, and Guggenheim. SC has consulted for GSK, JP Morgan, Citi, Morgan Stanley, Avalia NZ, Nutcracker Therapeutics, University of California, California State Universities, United Airlines, Adagio, and Roche. LJI has filed for patent protection for various aspects of T cell epitope and vaccine design work. All other authors declare no conflict of interest}, URL = {https://www.biorxiv.org/content/early/2022/03/21/2022.03.18.484953}, eprint = {https://www.biorxiv.org/content/early/2022/03/21/2022.03.18.484953.full.pdf}, journal = {bioRxiv} }