Kinetics and durability of humoral responses to SARS-CoV-2 infection and vaccination

We analyzed the kinetics and durability of the humoral responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and vaccination using >8,000 longitudinal samples collected over a three-year period (April 2020 – April 2023) in the New York City metropolitan area. Upon primary immunization, participants with pre-existing immunity mounted higher antibody responses faster and achieved higher steady-state levels compared to naïve individuals. Antibody durability was characterized by two phases: an initial rapid decay, followed by a phase of stabilization with very slow decay resulting in an individual spike binding antibody steady state. Booster vaccination equalized the differences in antibody levels between participants with and without hybrid immunity, but the antibody titers reached decreased with each successive antigen exposure. Break-through infections increased antibody titers to similar levels as an additional vaccine dose in naïve individuals. Our study provides strong evidence for the fact that SARS-CoV-2 antibody responses are long lasting, with an initial waning phase followed by a stabilization phase. ### Competing Interest Statement The Icahn School of Medicine at Mount Sinai has filed patent applications relating to SARS-CoV-2 serological assays and NDV-based SARS-CoV-2 vaccines which list Florian Krammer as co-inventor. Dr. Viviana Simon is also listed on the SARS-CoV-2 serological assays patent. Mount Sinai has spun out a company, Kantaro, to market serological tests for SARS-CoV-2. Florian Krammer has consulted for Curevac, Merck and Pfizer, and is currently consulting for 3rd Rock Ventures, GSK, Gritstone and Avimex and he is a co-founder and scientific advisory board member of CastleVax. The Krammer laboratory is also collaborating with Pfizer on animal models of SARS-CoV-2. ### Funding Statement This work was funded in part by the Centers of Excellence for Influenza Research and Surveillance (CEIRS, contract # HHSN272201400008C), the Centers of Excellence for Influenza Research and Response (CEIRR, contract # 75N93021C00014), by the Collaborative Influenza Vaccine Innovation Centers (CIVICs contract # 75N93019C00051), by philanthropic donations and by institutional funds including the Mount Sinai Center for Vaccine Research and Pandemic Preparedness. This effort was also in part supported by the Serological Sciences Network (SeroNet) in part with Federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. 75N91021F00001 via 21X092F1 Mod 01. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products or organizations imply endorsement by the U.S. Government. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study protocol IRB-20-03374 / STUDY-20-00442 was approved by the Institutional Review Board of the Mount Sinai Hospital. All study participants signed written consent forms prior to providing data or biospecimen. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors after publication