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Humoral and cellular immune memory to four COVID-19 vaccines

Zeli Zhang, Jose Mateus, Camila H. Coelho, Jennifer M. Dan, Carolyn Rydyznski Moderbacher, Rosa Isela Gálvez, Fernanda H. Cortes, Alba Grifoni, Alison Tarke, James Chang, E. Alexandar Escarrega, Christina Kim, Benjamin Goodwin, Nathaniel I. Bloom, April Frazier, Daniela Weiskopf, Alessandro Sette, Shane Crotty
doi: https://doi.org/10.1101/2022.03.18.484953
Zeli Zhang
1Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology (LJI), La Jolla, CA 92037, USA
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Jose Mateus
1Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology (LJI), La Jolla, CA 92037, USA
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Camila H. Coelho
1Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology (LJI), La Jolla, CA 92037, USA
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Jennifer M. Dan
1Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology (LJI), La Jolla, CA 92037, USA
2Department of Medicine, Division of Infectious Diseases and Global Public Health, University of California, San Diego (UCSD), La Jolla, CA 92037, USA
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Carolyn Rydyznski Moderbacher
1Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology (LJI), La Jolla, CA 92037, USA
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Rosa Isela Gálvez
1Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology (LJI), La Jolla, CA 92037, USA
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Fernanda H. Cortes
1Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology (LJI), La Jolla, CA 92037, USA
3Laboratory of AIDS and Molecular Immunology, Institute Oswaldo Cruz, Fiocruz, Rio de Janeiro, RJ 21040-360, Brazil
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Alba Grifoni
1Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology (LJI), La Jolla, CA 92037, USA
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Alison Tarke
1Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology (LJI), La Jolla, CA 92037, USA
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James Chang
1Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology (LJI), La Jolla, CA 92037, USA
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E. Alexandar Escarrega
1Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology (LJI), La Jolla, CA 92037, USA
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Christina Kim
1Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology (LJI), La Jolla, CA 92037, USA
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Benjamin Goodwin
1Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology (LJI), La Jolla, CA 92037, USA
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Nathaniel I. Bloom
1Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology (LJI), La Jolla, CA 92037, USA
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April Frazier
1Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology (LJI), La Jolla, CA 92037, USA
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Daniela Weiskopf
1Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology (LJI), La Jolla, CA 92037, USA
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  • For correspondence: daniela@lji.org alex@lji.org shane@lji.org
Alessandro Sette
1Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology (LJI), La Jolla, CA 92037, USA
2Department of Medicine, Division of Infectious Diseases and Global Public Health, University of California, San Diego (UCSD), La Jolla, CA 92037, USA
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  • For correspondence: daniela@lji.org alex@lji.org shane@lji.org
Shane Crotty
1Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology (LJI), La Jolla, CA 92037, USA
2Department of Medicine, Division of Infectious Diseases and Global Public Health, University of California, San Diego (UCSD), La Jolla, CA 92037, USA
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  • For correspondence: daniela@lji.org alex@lji.org shane@lji.org
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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.

Competing Interest Statement

A.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

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted March 21, 2022.
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Humoral and cellular immune memory to four COVID-19 vaccines
Zeli Zhang, Jose Mateus, Camila H. Coelho, Jennifer M. Dan, Carolyn Rydyznski Moderbacher, Rosa Isela Gálvez, Fernanda H. Cortes, Alba Grifoni, Alison Tarke, James Chang, E. Alexandar Escarrega, Christina Kim, Benjamin Goodwin, Nathaniel I. Bloom, April Frazier, Daniela Weiskopf, Alessandro Sette, Shane Crotty
bioRxiv 2022.03.18.484953; doi: https://doi.org/10.1101/2022.03.18.484953
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Humoral and cellular immune memory to four COVID-19 vaccines
Zeli Zhang, Jose Mateus, Camila H. Coelho, Jennifer M. Dan, Carolyn Rydyznski Moderbacher, Rosa Isela Gálvez, Fernanda H. Cortes, Alba Grifoni, Alison Tarke, James Chang, E. Alexandar Escarrega, Christina Kim, Benjamin Goodwin, Nathaniel I. Bloom, April Frazier, Daniela Weiskopf, Alessandro Sette, Shane Crotty
bioRxiv 2022.03.18.484953; doi: https://doi.org/10.1101/2022.03.18.484953

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