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Abstract
To assess vaccine immunogenicity in non-infected and previously infected individuals in a real-world scenario, SARS-CoV-2 antibody responses were determined during follow-up 2 (April 2021) of the population-based Tirschenreuth COVID-19 cohort study comprising 3378 inhabitants of the Tirschenreuth county aged 14 years or older. Seronegative participants vaccinated once with Vaxzevria, Comirnaty, or Spikevax had median neutralizing antibody titers ranging from ID50 = 25 to 75. Individuals with two immunizations with Comirnaty or Spikevax had higher median ID50s (of 253 and 554, respectively). Regression analysis indicated that both increased age and increased time since vaccination independently decreased RBD binding and neutralizing antibody levels. Unvaccinated participants with detectable N-antibodies at baseline (June 2020) revealed a median ID50 of 72 at the April 2021 follow-up. Previously infected participants that received one dose of Vaxzevria or Comirnaty had median ID50 to 929 and 2502, respectively. Individuals with a second dose of Comirnaty given in a three-week interval after the first dose did not have higher median antibody levels than individuals with one dose. Prior infection also primed for high systemic IgA levels in response to one dose of Comirnaty that exceeded IgA levels observed after two doses of Comirnaty in previously uninfected participants. Neutralizing antibody levels targeting the spike protein of Beta and Delta variants were diminished compared to the wild type in vaccinated and infected participants.
Highlights
There are four widely used COVID-19 vaccines in Europe and their immunogenicity has been assessed during clinical development [1–3] and post-marketing follow-up studies [4–7]
The antibody response after infection with SARS-CoV-2 was determined as a benchmark for the immunogenicity of vaccines
In sera from the April 2021 visit (T3), we evaluated the neutralizing and the spike protein receptor-binding domain (RBD) binding antibody levels (Roche Elecsys Anti-SARS-CoV-2 S test) after infection in individuals that were unvaccinated as well as in individuals that were vaccinated
Summary
There are four widely used COVID-19 vaccines in Europe and their immunogenicity has been assessed during clinical development [1–3] and post-marketing follow-up studies [4–7]. Assays, and time points of analysis hinder direct comparisons between the different vaccines. Investigations on the immune responses after mix-and-match regimens included conventional homologous immunizations enabling comparisons between different vaccines, but are limited to time points of analyses immediately after the second immunization and particular study populations younger than 60 years of age [8–11]. The cohort was established in June 2020 to assess seroprevalence for SARS-CoV-2 antibodies in the county of Tirschenreuth [12], which was one of the hardest-hit regions in Germany early during the pandemic. Two follow-up surveys including serum sampling and a questionnaire on the participants’ SARS-CoV-2 infection and vaccination history were performed in November 2020 and April 2021 with 3546 and 3391 participants, respectively. Dependence of the antibody responses on the age of vaccinees and on the time since the second immunization were of interest considering the current need for booster immunizations
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