Impact of Previous Common Human Coronavirus Exposure on SARS-CoV-2-Specific T-Cell and Memory B-Cell Response after mRNA-Based Vaccination

Abstract

Objective: T-cell responses against SARS-CoV-2 are observed in unexposed individuals, attributed to previous common human coronavirus (HCoV) infections. We evaluated the evolution of this T-cell cross-reactive response and the specific memory B-cells (MBCs) after the SARS-CoV-2 mRNA-based vaccination and its impact on incident SARS-CoV-2 infections. Methods: This was a longitudinal study of 149 healthcare workers (HCWs) that included 85 unexposed individuals that were subdivided according to previous T-cell cross-reactivity, who were compared to 64 convalescent HCWs. Changes in specific T-cell response and memory B-cell (MBC) levels were compared at baseline and after two doses of the SARS-CoV-2 mRNA-based vaccine. Results: A cross-reactive T-cell response was found in 59% of unexposed individuals before vaccination. Antibodies against HKU1 positively correlated with OC43 and 229E antibodies. Spike-specific MBCs was scarce in unexposed HCWs regardless of the presence of baseline T-cell cross-reactivity. After vaccination, 92% and 96% of unexposed HCWs with cross-reactive T-cells had CD4+ and CD8+ T-cell responses to the spike protein, respectively. Similar results to that were found in convalescents (83% and 92%, respectively). Contrarily, higher than that which was observed in unexposed individuals without T-cell cross-reactivity showed lower CD4+ and CD8+ T-cell responses (73% in both cases, p = 0.03). Nevertheless, previous cross-reactive T-cell response was not associated with higher levels of MBCs after vaccination in unexposed HCWs. During a follow-up of 434 days (IQR, 339–495) after vaccination, 49 HCWs (33%) became infected, with a significant positive correlation between spike-specific MBC levels and isotypes IgG+ and IgA+ after vaccination and a longer time to get infected. Interestingly, T-cell cross-reactivity did not reduce the time to vaccine breakthrough infections. Conclusion: While pre-existing T-cell cross-reactivity enhances the T-cell response after vaccination, it does not increase SARS-CoV-2-specific MBC levels in the absence of previous infection. Overall, the level of specific MBCs determines the time to breakthrough infections, regardless of the presence of T-cell cross-reactivity.

Effectiveness, Immunogenicity and Harms of Additional SARS-CoV-2 Vaccine Doses in Kidney Transplant Recipients: A Systematic Review

“…Due to the high methodological variance in investigating t-cell responses the results were highly heterogenous. As cellular responses are generally robust in the healthy population, the impaired cellular response in KTRs is likely provoked by MPA and other immunosuppressives affecting lymphocytes and thus preventing the generation of a broad immune response [64][65][66].…”

Tetanus-diphtheria vaccine can prime SARS-CoV-2 cross-reactive T cells

“…Adaptive immune responses to SARS-CoV-2 induced by both infection and vaccines are surely influenced by pre-existing cross-reactive immunity ( 19 – 22 ). Cross-reactive immunity occurs when memory T and B cells elicited by a primary encounter with pathogens/antigens recognize and respond to different pathogens/antigens ( 23 , 24 ).…”

Unbiased spectral cytometry immunome characterization predicts COVID-19 mRNA vaccine failure in older adults and patients with lymphoid malignancies

“…Indeed, although all of these vaccines induce systemic immune responses, little is known on their alterations from the immunological point of view. Hence, although the specific mechanisms of acquired humoral and cellular memory have been largely described, it has not been possible, up to date, to determine subsequent vaccine failure [1][2][3][4] .…”