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3100-12-31
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PRIOR SARS-COV-2 INFECTION ENHANCES INITIAL MRNA VACCINE RESPONSE WITH A LOWER IMPACT ON LONG-TERM IMMUNITY
Author
Affilliation
Center for Vaccines and Immunology. University of Georgia. Athens, GA/Florida Research and Innovation Center. Cleveland Clinic. Port Saint Lucie, FL.
Department of Immunology. St. Jude Children's Research Hospital. Memphis, TN.
Center for Vaccines and Immunology. University of Georgia. Athens, GA/Florida Research and Innovation Center. Cleveland Clinic. Port Saint Lucie, FL.
Monoclonal Antibody Discovery Lab. Foundation Toscana Life Sciences. Siena, Italy.
Monoclonal Antibody Discovery Lab. Foundation Toscana Life Sciences. Siena, Italy.
Monoclonal Antibody Discovery Lab. Foundation Toscana Life Sciences. Siena, Italy.
Fondazione Biotecnopolo di Siena. Siena, Italy.
Integrated Research Group in Biomarkers. René Rachou Institute. Oswaldo Cruz Foundation. Belo Horizonte, MG, Brazil.
Center for Vaccines and Immunology. University of Georgia. Athens, GA/Florida Research and Innovation Center. Cleveland Clinic. Port Saint Lucie, FL/Department of Infectious Diseases. University of Georgia. Athens, GA/Department of Infection Biology. Lerner Research Institute. Cleveland Clinic. Cleveland, OH.
Department of Immunology. St. Jude Children's Research Hospital. Memphis, TN.
Center for Vaccines and Immunology. University of Georgia. Athens, GA/Florida Research and Innovation Center. Cleveland Clinic. Port Saint Lucie, FL.
Monoclonal Antibody Discovery Lab. Foundation Toscana Life Sciences. Siena, Italy.
Monoclonal Antibody Discovery Lab. Foundation Toscana Life Sciences. Siena, Italy.
Monoclonal Antibody Discovery Lab. Foundation Toscana Life Sciences. Siena, Italy.
Fondazione Biotecnopolo di Siena. Siena, Italy.
Integrated Research Group in Biomarkers. René Rachou Institute. Oswaldo Cruz Foundation. Belo Horizonte, MG, Brazil.
Center for Vaccines and Immunology. University of Georgia. Athens, GA/Florida Research and Innovation Center. Cleveland Clinic. Port Saint Lucie, FL/Department of Infectious Diseases. University of Georgia. Athens, GA/Department of Infection Biology. Lerner Research Institute. Cleveland Clinic. Cleveland, OH.
Abstract
Spike-encoding mRNA vaccines in early 2021 effectively reduced SARS-CoV-2–associated morbidity and mortality. New booster regimens were introduced due to successive waves of distinct viral variants. Therefore, people now have a diverse immune memory resulting from multiple SARS-CoV-2 Ag exposures, from infection to following vaccination. This level of community-wide immunity can induce immunological protection from SARS-CoV-2; however, questions about the trajectory of the adaptive immune responses and long-term immunity with respect to priming and repeated Ag exposure remain poorly explored. In this study, we examined the trajectory of adaptive immune responses following three doses of monovalent Pfizer BNT162b2 mRNA vaccination in immunologically naive and SARS-CoV-2 preimmune individuals without the occurrence of breakthrough infection. The IgG, B cell, and T cell Spike-specific responses were assessed in human blood samples collected at six time points between a moment before vaccination and up to 6 mo after the third immunization. Overall, the impact of repeated Spike exposures had a lower improvement on T cell frequency and longevity compared with IgG responses. Natural infection shaped the responses following the initial vaccination by significantly increasing neutralizing Abs and specific CD4+ T cell subsets (circulating T follicular helper, effector memory, and Th1-producing cells), but it had a small benefit at long-term immunity. At the end of the three-dose vaccination regimen, both SARS-CoV-2–naive and preimmune individuals had similar immune memory quality and quantity. This study provides insights into the durability of mRNA vaccine-induced immunological memory and the effects of preimmunity on long-term responses.
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