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Generation and screening of a large collection of novel simian Adenovirus allows the identification of vaccine vectors inducing potent cellular immunity in humans

机译：产生和收集了大量的新型猿猴腺病毒的筛选允许疫苗载体的诱导在人类中有效的细胞免疫的识别

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Replication defective Adenovirus vectors based on the human serotype 5 (Ad5) have been shown to induce protective immune responses against diverse pathogens and cancer in animal models and to elicit robust and sustained cellular immunity in humans. However, most humans have anti-Ad5 neutralising antibodies that can impair the immunological potency of such vaccines. Here we show that most 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. To identify novel vaccine carriers suitable for vaccine delivery in humans we isolated and sequenced over a thousand Adenovirus strains from chimpanzees (ChAd). Replication-defective vectors were generated from different ChAd serotypes and were screened for neutralization by human sera and for ability to grow in human cell lines already approved for clinical studies. Most importantly, we devised a screening strategy to rank the ChAd vectors by immunological potency in mice which predicts their immunogenicity in non-human primates and humans. The vectors studied varied by up to a thousand-fold in potency for CD8 T cell induction in mice. Two of the most potent ChAd vectors were selected for clinical studies as carriers for Malaria and Hepatitis C virus (HCV) genetic vaccines. These ChAd vectors were found to be safe and immunologically potent in Phase I clinical trials thereby validating our screening approach. The ChAd vectors that we have developed represent a large collection of non cross-reactive, potent vectors that can be exploited for diverse vaccine strategies.

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