Maintenance of Broad Neutralising Antibodies and Memory B Cells 12 Months Post-Infection Is Predicted by SARS-CoV-2 Specific CD4+ T Cell Responses

Abstract

Understanding the long-term maintenance of SARS-CoV-2 immunity is critical for prediction of protection against reinfection. In a cohort of 24 participants, the association of disease severity and early immunological measurements on the maintenance of humoral immune responses 12 months post-infection were examined. All severely affected participants maintained a stable subset of SARS-CoV-2 receptor-binding domain (RBD) specific memory B cells (MBCs) and good neutralising antibody breadth against the majority of the variants of concern, including the Delta variant. Modelling these immune responses on vaccine efficacy data indicated a level equivalent to a vaccine efficacy of approximately 45-76% against symptomatic reinfection (variant dependent). Overall, these findings indicate durable humoral responses in most participants, provide an estimate of the level of protection and identifies the magnitude and phenotype of baseline antigen-specific CD4+ T cell response as a predictor of maintenance of both antibody neutralisation breadth and RBD-specific MBC levels at 12 months post-infection.Funding: The Kirby Institute is funded by the Australian Government Department of Health and Ageing. The views expressed in this publication do not necessarily represent the position of the Australian Government. Research reported in this publication was supported by Snow Medical Foundation as an investigator-initiated study. The content is solely the responsibility of the authors. RAB, MM, CR and ARL are fellows funded by National Health and Medical Research Council (NHMRC). MWAC is in part funded by the Research Infrastructure Programme of UNSW.Declaration of Interests: The authors declare no competing interests.Ethics Approval Statement: The protocol was approved by the Human Research Ethics Committees of the Northern Sydney Local Health District and the University of New South Wales, NSW Australia (ETH00520) and was conducted according to the Declaration of Helsinki and International Conference on Harmonization Good Clinical Practice (ICH/GCP) guidelines and local regulatory requirements. Written informed consent was obtained from all participants before study procedures.