Nonreplicating vectors in HIV vaccines.
OBJECTIVE
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.


RESULTS
The success of the RV144 trial, with a canarypox virus-based regimen, contrasts with the failures of the adenovirus-5 (Ad5)-based regimens in the Step study, the Phambili study [HIV Vaccine Trials Network (HVTN) 503], and the HVTN 505 study which was recently modified to halt vaccinations because of clinical futility.


CONCLUSIONS
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 nonhuman adenoviruses, provide additional avenues for exploration.
Division of Infectious Diseases, Brigham and Women's Hospital, Beth Israel Deaconess Medical Center cHarvard Medical School, Boston, Massachusetts 02115, USA. jjohnson30@partners.org
Jennifer A
JA
Johnson
Dan H
DH
Barouch
Lindsay R
LR
Baden
D016915:AIDS Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000235:genetics* / Q000276:immunology*; D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D028121:Canarypox virus / Q000235:genetics; D002986:Clinical Trials as Topic; D004337:Drug Carriers; D004353:Drug Evaluation, Preclinical; D005822:Genetic Vectors; D015658:HIV Infections / Q000517:prevention & control*; D006801:Humans; D018155:Orthopoxvirus / Q000235:genetics; D016896:Treatment Outcome
D016915:AIDS Vaccines; D004337:Drug Carriers