Efficacy, safety, and biodistribution of intranasally delivered adenoviral COVID-19 vaccine in hamsters
TL;DR
It is confirmed that mucosal delivery leads to effective protection against infection in hamsters and support that intranasal delivery is a promising approach for mucosal vaccine administration against respiratory infection pathogens and extend the knowledge of Adeno-vector persistence.
Abstract
Coronavirus disease 2019 (COVID-19) continues to cause outbreaks around the world despite the vast COVID-19 vaccination programs. Thus, it is important to continue developing better vaccines to protect vulnerable populations. Here, we studied the efficacy, safety, persistence and biodistribution of an adenovirus-based COVID-19 vaccine delivered intranasally. Our results confirmed that mucosal delivery leads to effective protection against infection in hamsters. A comparative study of different adenoviral vectors demonstrated that specifically Ad5-S-3M, expressing the SARS-CoV-2 spike glycoprotein ectodomain with inclusion of three common receptor binding domain mutations, induced a robust humoral immune response and effectively protected hamsters from SARS-CoV-2 infection. In addition, longitudinal analysis of vaccinated hamsters’ tissues demonstrated durable vaccine transgene expression and persistent vector DNA in the nasal turbinates. This persistence may be beneficial in increasing the duration of immunity. Expression of the S-3M did not cause any aberrant changes in the hamster tissues and resulted in very few changes in cellular mRNA expression in target tissues. Safety and biodistribution assessment demonstrated restricted non-target tissue distribution of intranasally delivered vector and no significant changes in clinical blood chemistry, underlining the safety of the vaccine. These results further support that intranasal delivery is a promising approach for mucosal vaccine administration against respiratory infection pathogens and extend our knowledge of Adeno-vector persistence.