Purpose of review We review the broad spectrum of nonreplicating viral vectors which have been studied extensively, from preclinical studies through clinical efficacy trials, and include some of our most promising HIV vaccine candidates. Recent findings The success of the RV144 trial, with an ALVAC (canarypox)-based regimen, contrasts with the failures of the Adenovirus 5-based regimens in the Step study, the Phambili study (HVTN 503), and the HVTN 505 study which was recently modified to halt vaccinations due to clinical futility. Summary The safety profile, immunogenicity, and variety of available candidates make the nonreplicating viral vectors attractive in HIV vaccine development. Building from the success of the RV144 study, further studies of Orthopoxvirus-based vaccines, including Vaccinia-based vaccines, are ongoing and planned for the future. Despite the failures of the Ad5-based vaccines in clinical efficacy trials, other adenovirus serotypes remain promising candidates, especially in prime-boost combination with other products, and with the potential use of mosaic inserts. Other nonreplicating viral vectors such as the rhabdoviruses, alphaviruses and the non-human adenoviruses, provide additional avenues for exploration.
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