ABSTRACT
It is uncertain to which extent antibody and T-cell responses after vaccination against SARS-CoV-2 are associated with reduced risk of breakthrough infection and whether their measurement enhances risk prediction. We conducted a phase-4 open-label clinical trial in the pre-omicron era, enrolling 2,760 individuals aged [≥]16 years 35{+/-}8 days after having received the second dose of BNT162b2 (baseline 15-21 May 2021). Over a median 5.9-month of follow-up, we identified incident SARS-CoV-2 breakthrough infections using weekly antigen tests, a confirmatory PCR test, and/or serological evidence for incident infection. We quantified relative risks adjusted for age, sex, and prior SARS-CoV-2 infection for different immunological parameters and assessed improvements in risk discrimination. In contrast to the T-cell response, higher plasma levels of binding antibodies and antibodies in a surrogate neutralization assay were associated with reduced risk of breakthrough infection. Furthermore, assessment of anti-spike IgG levels enhanced prediction of breakthrough infection and may therefore be a suitable measurable correlate of protection in practice.
ABSTRACT
BackgroundIn early March 2020, a SARS-CoV-2 outbreak in the ski resort Ischgl in Austria initiated the spread of SARS-CoV-2 throughout Austria and Northern Europe. In a cross-sectional study, we found that the seroprevalence in the adult population of Ischgl had reached 45% by the end of April. To answer the question of how long immunity persists and what effect this high-level immunity had on virus transmission, we performed a follow-up study in early November, 2020. MethodsOf the 1259 adults that participated in the baseline study, 801 could be included in the follow-up. The study involved the analysis of binding and neutralizing antibodies and T cell responses. In addition, the incidence of SARS-CoV-2 infections in Ischgl was compared to the incidence in similar municipalities in Tyrol throughout 2020. FindingsFor the 801 individuals that participated in both studies, the seroprevalence declined from 51.4% (95% confidence interval (CI) 47.9 - 54.9) to 45.4% (95% CI 42.0 - 49.0). Median antibody concentrations dropped considerably but antibody avidity increased. T cell responses were analysed in 93 cases, including all 4 formerly seropositive cases that had lost antibodies in all assays, three of which still had detectable T cell memory. In addition, the incidence in the second COVID-19 wave that hit Austria in November 2020, was significantly lower in Ischgl than in comparable municipalities in Tyrol or the rest of Austria. InterpretationThis study has important implications as it shows that although antibodies to SARS-CoV-2 declined, T and B cell memory can be detected for up to 8 months. Complemented by infection prevention measures a level of around 40-45% immunity in Ischgl significantly reduced local virus transmission during the second wave in Austria in November 2020. FundingFunding was provided by the government of Tyrol and the FWF Austrian Science Fund.
