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

• Published in: Viruses Vol. 15; no. 3; p. 627
• Main Authors: Casado, José L, Vizcarra, Pilar, Martín-Hondarza, Adrián, Blasco, Magdalena, Grandal-Platero, Marta, Haemmerle, Johannes, Fernández-Escribano, Marina, Vallejo, Alejandro
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 24-02-2023; MDPI
• Subjects: Antibodies; Antibodies, Viral; B cells; Breakthrough Infections; CD4 antigen; CD8 antigen; coronavirus; Coronaviruses; COVID-19 - prevention & control; COVID-19 vaccines; cross-reactive; Cross-reactivity; Flow cytometry; Health aspects; Humans; Immunoglobulin A; Immunoglobulin G; Immunological memory; Infections; Isotypes; Longitudinal Studies; Lymphocytes B; Lymphocytes T; Medical personnel; memory B-cells; Memory cells; mRNA; mRNA vaccine; Proteins; RNA, Messenger; SARS-CoV-2; SARS-CoV-2 - genetics; Serology; Severe acute respiratory syndrome coronavirus 2; Spike Glycoprotein, Coronavirus - genetics; Spike protein; T cells; Vaccination; Vaccines; Spain; United States > US; Germany; memory B-cells; coronavirus; SARS-CoV-2; cross-reactive; mRNA vaccine
• ISSN: 1999-4915; 1999-4915
• DOI: 10.3390/v15030627

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.
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.
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,
= 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.
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.