Stephenson, KathrynBarouch, Dan2014-03-112013Stephenson, Kathryn E., and Dan H Barouch. 2013. “A global approach to HIV-1 vaccine development.” Immunological Reviews 254 (1): 295-304. doi:10.1111/imr.12073. http://dx.doi.org/10.1111/imr.12073.0105-2896http://nrs.harvard.edu/urn-3:HUL.InstRepos:11879922Summary A global human immunodeficiency virus-1 (HIV-1) vaccine will have to elicit immune responses capable of providing protection against a tremendous diversity of HIV-1 variants. In this review, we first describe the current state of the HIV-1 vaccine field, outlining the immune responses that are desired in a global HIV-1 vaccine. In particular, we emphasize the likely importance of Env-specific neutralizing and non-neutralizing antibodies for protection against HIV-1 acquisition and the likely importance of effector Gag-specific T lymphocytes for virologic control. We then highlight four strategies for developing a global HIV-1 vaccine. The first approach is to design specific vaccines for each geographic region that include antigens tailor-made to match local circulating HIV-1 strains. The second approach is to design a vaccine that will elicit Env-specific antibodies capable of broadly neutralizing all HIV-1 subtypes. The third approach is to design a vaccine that will elicit cellular immune responses that are focused on highly conserved HIV-1 sequences. The fourth approach is to design a vaccine to elicit highly diverse HIV-1-specific responses. Finally, we emphasize the importance of conducting clinical efficacy trials as the only way to determine which strategies will provide optimal protection against HIV-1 in humans.en-USHIVvaccinesviral diversityimmune responsesJournal Article2014-03-1110.1111/imr.12073