Pre-clinical testing of two serologically distinct chimpanzee-origin adenovirus vectors expressing spike of SARS-CoV-2

Abstract

AbstractTwo serologically distinct chimpanzee-origin, replication-defective adenovirus (AdC) vectors expressing the spike (S) protein of an early severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) isolate were generated and tested for induction of antibodies in mice. Both vectors induced S protein-specific antibodies including neutralizing antibodies. Levels of antibodies increased after a boost. The effectiveness of the boost depended on vector dose, timing between the two immunizations and the use of homologous versus heterologous AdC vectors. Virus neutralizing antibodies (VNAs) showed only a slight loss of reactivity against variants, which may reflect the pronounced responses against the more conserved S2 subunit of the S protein. Expression of two different S proteins by the AdC vectors used for the prime and the boost did not selectively increase responses against the variants. A vector expressing the fusion peptide of the S2 protein induced highly cross-reactive VNA responses, which, nevertheless, were not sustained.