Anti-Ad26 humoral immunity does not compromise neutralizing antibody responses following Ad26-based booster vaccination with Gam-COVID-Vac

Abstract Replication-incompetent adenoviral vectors have been extensively used as a platform for vaccine design, with at least four anti-COVID-19 vaccines authorized to date. These vaccines elicit a neutralizing antibody response directed against SARS-CoV-2 Spike protein and confer significant level of protection against SARS-CoV-2 infection. Immunization with adenovirus-vectored vaccines is known to be accompanied with the production of anti-vector antibodies, which may translate into reduced efficacy of booster or repeated rounds of vaccination. Here, we used adenovirus-based Gam-COVID-Vac vaccination to address the question of whether anti-vector antibodies may influence the magnitude of SARS-CoV-2-specific humoral response after booster vaccination. We observed that Ad26-based prime vaccination with Gam-COVID-Vac induced the development of Ad26-neutralizing antibodies which persisted in circulation for at least 9 months. Our analysis indicates that high pre-boost Ad26 neutralizing antibody titers do not appear to affect the humoral immunogenicity of the Gam-COVID-Vac boost. The titers of anti-SARS-CoV-2 RBD IgGs and antibodies which neutralized both the wild type and the circulating variants of concern of SARS-CoV-2 such as Delta and Omicron, were independent of the pre-boost levels of Ad26-neutralizing antibodies. Thus, our results support the development of repeated immunization schedule with adenovirus-based COVID-19 vaccines.