Abstract

Cancer patients display reduced humoral responses after initial COVID-19 vaccination. Although vaccination protects against severe COVID-19, T cell immunity is impaired in cancer patients. In recent studies, booster vaccines provide additional protection against SARS-CoV-2. However, more data is needed on different vaccination schedules. This prospective study compares BNT162b2 booster-vaccination after primo-vaccination with BNT162b2 (homologous) versus ChAdOx1 (heterologous) in cancer patients. 441 subjects (314 cancer patients and 127 healthy individuals) received a 3rd dose BNT162b2 (229 homologous vs 212 heterologous) 6-9 months after priming. Vaccine induced adverse events (AE) were captured up to 7 days after vaccination. Humoral immunity was assessed by SARS-CoV-2 anti-S1 IgG antibody levels and SARS-CoV-2 50% neutralization titers (NT50) for Wuhan and Omicron strains. Cellular immunity was examined by analyzing CD4 and CD8 T cell responses against SARS-CoV-2 specific S1 and S2 peptides. All assays were performed on blood samples collected 28 days after 3rd dose. Local AEs were more common after heterologous boosting, while no significant differences were seen for systemic AEs. SARS-CoV-2 anti-S1 IgG antibody levels did not differ significantly between homologous and heterologous boosted subjects (GMT 1755.90 BAU/ml [95% C) 1276.95-2414.48] vs 1495.82 BAU/ml (95% CI 1131.48-1977.46)). However, homologously boosted subjects show significantly higher NT50 values against Omicron. T cell responses were assessed by CD154 (CD40L) and CD137 expression on CD4 and CD8 T cells as general markers of antigen-specific stimulation. Here, no significant differences in T cell responses and cytokine levels of IFNγ, IL-2 and TNFα were observed between both boosting regimens. Homologous and heterologous boosted patients elicit similar SARS-CoV-2 anti-S1 IgG antibody levels. Yet, heterologous boosted subjects report more local AEs and homologous boosted subjects show significantly higher NT50 values against Omicron. No difference between T cell responses in heterologous and homologous boosted cohorts was observed.

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