Chamcha, VenkateswarluKannanganat, SunilGangadhara, SailajaNabi, RafiqKozlowski, Pamela A.Montefiori, David C.LaBranche, Celia C.Wrammert, JensKeele, Brandon F.Balachandran, HarikrishnanSahu, SujataLifton, MichelleSantra, SampaBasu, RahulMoss, BernardRobinson, Harriet L.Amara, Rama Rao2016-04-012016Chamcha, V., S. Kannanganat, S. Gangadhara, R. Nabi, P. A. Kozlowski, D. C. Montefiori, C. C. LaBranche, et al. 2016. “Strong, but Age-Dependent, Protection Elicited by a Deoxyribonucleic Acid/Modified Vaccinia Ankara Simian Immunodeficiency Virus Vaccine.” Open Forum Infectious Diseases 3 (1): ofw034. doi:10.1093/ofid/ofw034. http://dx.doi.org/10.1093/ofid/ofw034.2328-8957http://nrs.harvard.edu/urn-3:HUL.InstRepos:26318530Background. In this study, we analyzed the protective efficacy of a simian immunodeficiency virus (SIV) macaque 239 (SIVmac239) analogue of the clinically tested GOVX-B11 deoxyribonucleic acid (DNA)/modified vaccinia Ankara (MVA) human immunodeficiency virus vaccine. Methods. The tested vaccine used a DNA immunogen mutated to mimic the human vaccine and a regimen with DNA deliveries at weeks 0 and 8 and MVA deliveries at weeks 16 and 32. Twelve weekly rectal challenges with 0.3 animal infectious doses of SIV sootey mangabey E660 (SIVsmE660) were administered starting at 6 months after the last immunization. Results. Over the first 6 rectal exposures to SIVsmE660, <10-year-old tripartite motif-containing protein 5 (TRIM5)α-permissive rhesus macaques showed an 80% reduction in per-exposure risk of infection as opposed to a 46% reduction in animals over 10 years old; and, over the 12 challenges, they showed a 72% as opposed to a 10% reduction. Analyses of elicited immune responses suggested that higher antibody responses in the younger animals had played a role in protection. Conclusions. The simian analogue of the GOVX-B11 HIV provided strong protection against repeated rectal challenges in young adult macaques.en-USage-dependent protectionantibodyDNA/MVA vaccineHIV vaccineSIVJournal Article2016-04-0110.1093/ofid/ofw034