Immunological Memory to Common Cold Coronaviruses Assessed Longitudinally Over a Three-Year Period

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Abstract
Immune memory to Common Cold Coronaviruses (CCCs) influences SARS-CoV-2 infection outcome, and is crucial for pan-corona vaccine development. We performed a longitudinal analysis of pre-pandemic samples collected from 2016-2019, and assessed CCC-specific CD4+ T cell and antibody responses, comparing to other respiratory viruses and ubiquitous pathogens. Notably, CCC responses were detected in most subjects, with comparable frequencies as other common antigens, and were sustained over time. CCC-specific CD4+ T cell responses were associated with low HLA-DR+CD38+ cell quantity and their magnitude did not correlate with yearly changes in CCC infection prevalence. Similarly, CCC-specific spike RBD-specific IgG responses were stable throughout the sampling period. Finally, high CCC-specific CD4+ T cell reactivity, but not antibody titers, was associated with pre-existing SARS-CoV-2 immunity. These results suggest that steady and sustained CCC responses are likely from a stable pool of memory CD4+ T cells, due to repeated earlier exposures and possibly occasional reinfections.

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