Due to the low sample number, there were insufficient data to assess the T-cell correlation patterns for this group (Number?3a and b). Open in a separate window Figure 2 Factors associated with March 2022 S- or N-IgG, N-Ab titers, or S- or M/N-T cell IFN-gamma levels. sensitive measure of viral exposure. Large N-IgG titers, Omicron-N-Ab activity, and S-specific-T-cell reactions were all associated with a reduced probability of (re)illness over time. Summary Population-level SARS-CoV-2 immunity is definitely JNJ-17203212 S-IgG-dominated, but heterogeneous. M/N-T-cell reactions can distinguish earlier illness from vaccination, and monitoring a combination of N-IgG, Omicron-N-Ab, and S-T-cell reactions may help estimate safety against SARS-CoV-2 (re)illness. Keywords: SARS-CoV-2, Cross immunity, Seroprevalence, Neutralizing antibodies, T cell reactions, Interferon-gamma launch assay Introduction It is right now well-understood that exposure to SARS-CoV-2 elicits strong antibody (Ab) and T cell-mediated immune reactions to multiple viral proteinsin particular JNJ-17203212 spike (S), nucleocapsid (N), and membrane (M) proteins [1], [2], [3], [4], [5]. In contrast to illness, the messenger RNA-based COVID-19 vaccines used widely in the United States and Europe elicit reactions to the viral S protein; the Rabbit Polyclonal to SCARF2 only antigenic component of these vaccines [6,7]. As the correlate(s) of safety needed to prevent illness or severe illness have yet to be clearly defined [8], data on population-level humoral and cellular immune responsiveness to SARS-CoV-2 remain important for understanding (i) the scope of viral exposure and (ii) what proportion of the population possesses some degree of virus-specific immunity. Although much is now known concerning population-level Ab reactions to SARS-CoV-2 illness, our understanding of T cell-mediated immunity is much less comprehensive. JNJ-17203212 T-cell reactions have been explained following both vaccination [9], [10], [11], [12], [13] and illness, including slight or asymptomatic JNJ-17203212 instances actually without seroconversion [1], [2], [3],5,[13], [14], [15], [16]. However, extensive studies of T-cell reactions, particularly at the population level, are lacking, partially due to the labor-intensive and relatively low-throughput nature of assays designed to evaluate them, such as enzyme-linked immunospot (ELISpot) and circulation cytometry-based assays. To address this, adaptation of interferon (IFN)-gamma launch assays (IGRAs), such as those used in and Cytomegalovirus screening [17,18], may aid in the detection of SARS-CoV-2-specific T cells in a larger quantity of samples. Importantly, as both humoral and cellular reactions contribute to immunity against SARS-CoV-2, a better understanding of the heterogeneous mixtures of immune memory space which can protect against disease may help to inform vaccination strategies, including the administration of additional booster vaccine doses. Here, we carried out a population-based cohort study evaluating Ab and T-cell reactions to SARS-CoV-2 among individuals aged 16+ in Zurich, Switzerland, including individuals of varying vaccination and illness statuses. In March 2022, for those study participants (n?=?1044) we evaluated total SARS-CoV-2 S- and N-immunoglobulin(Ig)G Ab levels, as well while neutralizing Ab (N-Ab) activity to wildtype (WT) computer virus, Delta, and Omicron variants using a surrogate neutralization assay. Inside a randomly selected subset of individuals (n?=?328), we further assessed T-cell reactions to S, M, and N proteins by IGRA. To investigate longitudinal changes in immune reactions over time we reassessed Ab (n?=?964) and T cell (n?=?141) reactions 3 months later, in June 2022. Overall, we found unique immune response patterns among participants depending on the reported illness and vaccination statuses. Already at the beginning of the study, nearly all participants experienced detectable S-IgG reactions. In contrast, N-IgG and M/N-specific T-cell reactions increased significantly over time, despite existing S-IgG, indicating viral (re)exposure. Importantly, participants with the highest N-IgG titers and Omicron-N-Ab activity, and those with IFN-gamma-producing S-reactive T cells all experienced significantly reduced probability of (re)illness between March and June 2022. Collectively, our results indicate that population-level immune reactions to SARS-CoV-2 are S-IgG-dominated but heterogeneous. They suggest a role for assessing M/N-specific T cells in estimating earlier viral exposure and further suggest that monitoring a combination of N-IgG, Omicron-N-Ab, and S-reactive T-cell reactions may help to forecast population-level safety against Omicron SARS-CoV-2 (re)illness. Abbreviated methods Complete information and methods on statistical analyses are available in the supplementary materials. Participant test and recruitment collection People aged 16+ surviving in the canton of Zurich, Switzerland were arbitrarily chosen by age-stratified intervals from a inhabitants registry and asked to participate. Altogether, 4875 individuals had been approached and 1044 enrolled (21.4% involvement, Supplementary Body 1). Initial research visits were executed from March 1st through 31st, 2022 and second research trips (964/1044, 92.3% involvement, Supplementary Body 1) were executed from June 7th through July 11th, 2022. At each go to, individuals provided information relating to prior COVID-19 vaccination and positive SARS-CoV-2 exams. From each participant, 10 ml of venous bloodstream was gathered and plasma was cryopreserved before evaluation of S-Ig.
