SARS-CoV-2-specific T cell responses: a comparative analysis between QuantiFERON SARS-CoV-2, T-SPOT.COVID, and an in-house Omicron ELISpot.

BACKGROUND: T cell immunity plays a pivotal role in mitigating the severity of coronavirus disease 2019 (COVID-19). Therefore, reliable functional T cell assays are required to evaluate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T cell immunity in specific patient populations. METHODS: We recruited a cohort of 23 healthcare workers who received their bivalent Omicron BA.1 / ancestral mRNA booster vaccination or were infected with the Omicron variant at a median of 144 days and 227 days before blood collection, respectively. In this cohort, we compared the performances of two widely utilized commercial SARS-CoV-2 interferon-gamma release assays (IGRAs), i.e., QuantiFERON SARS-CoV-2 and T-SPOT.COVID, and an in-house designed Omicron enzyme-linked immunospot (ELISpot). RESULTS: The QuantiFERON SARS-CoV-2 and T-SPOT.COVID assays detected SARS-CoV-2 spike-specific T cells in 34.8 % and 21.7 % of participants, respectively. Moreover, our in-house designed ELISpot that included Omicron BA.4 and BA.5 full-spike peptides detected T cell responses in 47.8 % of participants and was strongly associated with the T-SPOT.COVID. CONCLUSION: The evaluation of SARS-CoV-2 T cell immunity using commercially accessible assays may yield disparate outcomes as results from different assays are not directly comparable. A specific Omicron ELISpot should be considered to assess Omicron-specific T cell immunity.

Ancestral SARS-CoV-2 and Omicron BA.5-specific neutralizing antibody and T-cell responses after Omicron bivalent booster vaccination in previously infected and infection-naive individuals.

Coronavirus disease-2019 (COVID-19) bivalent ancestral/Omicron messenger RNA (mRNA) booster vaccinations became available to boost and expand the immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron infections. In a prospective cohort study including 59 healthcare workers, we assessed SARS-CoV-2 ancestral and Omicron BA.5-specific neutralizing antibody and T-cell responses in previously infected and infection-naive individuals. Also, we assessed the effect of an ancestral/Omicron BA.1 bivalent mRNA booster vaccination on these immune responses. 10 months after previous monovalent mRNA vaccinations, ancestral SARS-CoV-2 S1-specific T-cell and anti-RBD IgG responses remained detectable in most individuals and a previous SARS-CoV-2 infection was associated with increased T-cell responses. T-cell responses, anti-RBD IgG, and Omicron BA.5 neutralization activity increased after receiving an ancestral/Omicron BA.1 bivalent booster mRNA vaccination. An Omicron BA.5 infection in addition to bivalent vaccination, led to a higher ratio of Omicron BA.5 to ancestral strain neutralization activity compared to no bivalent vaccination and no recent SARS-CoV-2 infection. In conclusion, SARS-CoV-2 T-cell and antibody responses persist for up to 10 months after a monovalent booster mRNA vaccination. An ancestral/Omicron BA.1 bivalent booster mRNA vaccination increases these immune responses and also induces Omicron BA.5 cross-neutralization antibody activity. Finally, our data indicate that hybrid immunity is associated with improved preservation of T-cell immunity.