The role of naturally occurring and vaccine-induced Ad26 neutralizing antibodies in immunogenicity of Ad26-based vaccines

Adenovirus 26 (Ad26) is frequently used as a vaccine vector targeting infectious diseases. Neutralizing antibodies (NAbs) induced by natural infection or immunization against some viral vaccine vectors may impact vaccine-induced immunogenicity and efficacy. We evaluated the natural seroprevalence and impact of Ad26 NAbs on vaccine immunogenicity using data combined from 21 clinical studies including 3851 participants from 15 countries. Ad26 NAb seroprevalence was higher in Africa than the United States and Europe. An inconsistently observed, clinically negligible negative trend was observed between naturally occurring Ad26 NAbs and vaccine-induced immune responses in participants who received Ad26-based Ebola or HIV vaccine regimens. Assessment of the impact of vaccine-induced anti-vector immunity after repeated vaccination found that an Ad26-based COVID-19 vaccine received 1-12 months before an Ad26-based RSV vaccine did not seem to impact post vaccination RSV immune responses. Within the study limitations, our data suggest that Ad26-based vaccines can be used in countries with high Ad26 seroprevalence and for repeated vaccination without compromising the vaccine antigen-induced immune response.