Recent Advances in Adenovirus-Vectored Vaccines Development
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.
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.
Vaccine Ad35-TBS (or AERAS-402) consists of recombinant replication-defective
HAdV-35 vector expressing M.tb antigens Ag85A, Ag85B and TB10.4 as a single fusion protein.
A phase 1 trial in healthy Bacillus Calmette-Guerin (BCG)-vaccinated adults
in South Africa demonstrated that the vaccine is safe and immunogenic.
In addition, the vaccine safety and immunogenicity has been
reported in healthy adults living in the US. In the study, volunteers
were primed with BCG three or six months prior to AERAS-402 boosting. Also, AERAS-402
was safe and immunogenic in healthy infants previously vaccinated with BCG at birth.
Vaccin Res Open J. 2017; 2(1): e2-e4. doi: 10.17140/VROJ-2-e004