2012 Science Translational Medicine Vol. 4, Issue 115. 115ra2
Colloca S, Barnes E, Folgori A, Ammendola V, Capone S, Cirillo A, Siani L, Naddeo M, Grazioli F, Esposito ML, Ambrosio M, Sparacino A, Bartiromo M, Meola A, Smith K, Kurioka A, O'Hara GA, Ewer KJ, Anagnostou N, Bliss C, Hill AV, Traboni C, Klenerman P, Cortese R, Nicosia A
In the quest for novel vaccines against chronic infectious diseases (ie: HIV, HCV, Tuberculosis) and cancer, the use of genes as vaccines (genetic vaccination) is a promising strategy because it efficiently stimulates both arms of the adaptive immune system. Adenoviruses are particularly efficient for the induction of CD8 effector and memory responses, a feature that is often missing when ‘traditional’ protein-based vaccines are used. However, most humans have anti-Ad5 neutralising antibodies that can impair the immunological potency of such a vector for human vaccine delivery. Other human Adenoviruses from rare serotypes are far less potent as vaccine vectors than Ad5 in mice and non-human primates, casting doubt on their potential efficacy in humans.
In the published work by Colloca et al., we have addressed the issue of lack of suitable Adenovirus by generating a ‘library’ of replication incompetent Adenovirus vectors isolated from chimpanzees (ChAd). Screening of this library by a combination of in vitro and in vivo approaches led to the identification of several candidates that are not neutralised by antibodies present in humans, have high immunological potency and can be produced in human cell lines approved by regulatory agencies. In a recent unpublished work, we have also shown that ChAd can protect from infection by different pathogens (RSV, Influenza, Ebola) in relevant animal models and can be considered suitable candidate carriers for vaccine delivery in humans. Consistently, two of the most potent ChAd vectors were selected for clinical studies as carriers for Malaria and Hepatitis C virus genetic vaccines where they proved to be safe and immunologically very potent.
In non human primates and in humans ChAd are extremely effective at priming immune responses that develop into long-term memory responses and are readily re-expanded in vivo by second encountering with the encoded pathogenic antigen. This feature can also be exploited by using ChAd vectors in heterologous prime/boost regimens with different ChAd vectors, or with different vaccine platforms (other vectors, naked DNA or proteins) as boosters.
In summary, ChAd vectors represent a platform technology that can be exploited for diverse vaccine strategies against infectious diseases and cancer.