Recent Advances in Adenovirus-Vectored Vaccines Development

Abstract

Recombinant adenovirus-vectored vaccines based on human adenovirus serotype 5 (HAdV-5) have been extensively studied both pre-clinically and in clinical trials for the past 25 years. Initially, they were considered as the most promising platform for human immunodeficiency virus (HIV) vaccine development. However, HAdV-5-based vaccine did not meet expectations in a large-scale clinical trial called STEP trial.1 In that trial, the vaccine not only showed lack of efficacy, but also suggested an increased trend for HIV acquisition in individuals with pre-existing HAdV-5 neutralizing antibodies.

Researches have developed vectors based on alternative serotypes of human and non-human adenoviruses in order to overcome challenges with HAd5-based vectors. To date, HAdV-35, HAdV-26 and simian adenoviruses ChAd3, ChAd63 and ChAdOx1 have been tested in several phase 1 clinical trials as candidate vaccine component against Mycobacterium tuberculosis, Plasmodium falciparum, HIV, Ebola, HCV and influenza virus. These vectors were chosen because most people have little or no immunity to them, and their biological characteristics, such as utilization of primary cellular receptor and elicitation of innate cytokine responses, differ from HAdV-5.