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Here we show that Ad prime, Env protein boost vaccines protect against neutralization-resistant SIVsmE660 variants. We perform two studies in rhesus monkeys with Ad35\/Ad26 vectors expressing SIVmac239 Gag\/Pol\/Env with or without an AS01<jats:sub>B<\/jats:sub>-adjuvanted SIVmac32H gp140 protein boost. In a repetitive, low-dose challenge study, we observe robust protection against acquisition of infection by both Ad Alone and Ad\/Env vaccines. In a single, high-dose challenge study, only the Ad\/Env vaccine affords significant protection against acquisition of infection. Analysis of transmitted\/founder (T\/F) viruses from this study demonstrates that the Ad\/Env vaccine blocks both neutralization-sensitive and neutralization-resistant SIVsmE660 variants in rhesus monkeys with restrictive TRIM5\u03b1 alleles. These data demonstrate that the adjuvanted Env protein boost is critical for protecting against high-dose SIVsmE660 challenge and for blocking neutralization-resistant viruses within the SIVsmE660 swarm.<\/jats:p>","DOI":"10.1038\/ncomms15740","type":"journal-article","created":{"date-parts":[[2017,6,5]],"date-time":"2017-06-05T12:15:13Z","timestamp":1496664913000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Adenovirus prime, Env protein boost vaccine protects against neutralization-resistant SIVsmE660 variants in rhesus monkeys"],"prefix":"10.1038","volume":"8","author":[{"given":"Brandon F.","family":"Keele","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5335-7386","authenticated-orcid":false,"given":"Wenjun","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erica N.","family":"Borducchi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph P.","family":"Nkolola","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1978-088X","authenticated-orcid":false,"given":"Peter","family":"Abbink","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bing","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael S.","family":"Seaman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dan H.","family":"Barouch","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2017,6,5]]},"reference":[{"key":"BFncomms15740_CR1","doi-asserted-by":"publisher","first-page":"81ra36","DOI":"10.1126\/scitranslmed.3002351","volume":"3","author":"NL Letvin","year":"2011","unstructured":"Letvin, N. 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