title: Long-term vaccine protection from AIDS and clearance of viral DNA following SHIV89.6P challenge.
abstract: In an earlier study, our group vaccinated rhesus macaques with vesicular stomatitis virus (VSV) vectors expressing Gag, Pol, and Env proteins from a hybrid simian/human immunodeficiency virus (SHIV). This was followed by a single boost with modified vaccinia virus Ankara (MVA) vectors expressing the same proteins. Following challenge with SHIV89.6P, vaccinated animals cleared challenge virus RNA from the blood by day 150 and maintained normal CD4 T cell counts for 8 months. Here we report on the long-term (>5-year post-challenge) status of these animals and the immunological correlates of long-term protection. Using real-time PCR, we found that viral DNA in peripheral blood mononuclear cells (PBMCs) of the vaccinees declined continuously and fell to below detection (<5copies/10(5)cells) by approximately 3 years post-challenge. SHIV DNA was also below the limit of detection in the lymph nodes of two of the four animals at 5 years post-challenge. We detected long-term persistence of multi-functional Gag-specific CD8(+) T cells in both PBMCs and lymph nodes of the two protected animals with the Mamu A01(+) MHC I allele. All animals also maintained SHIV89.6P neutralizing antibody titers for 5 years. Our results show that this vaccine approach generates solid, long-term control of SHIV infection, and suggest that it is mediated by both cytotoxic T lymphocytes and neutralizing antibody.
authors.affiliation: Yale University School of Medicine, New Haven, CT, United States.
authors.forename: John
authors.initials: J
authors.lastname: Schell
authors.forename: Nina F
authors.initials: NF
authors.lastname: Rose
authors.forename: Nicole
authors.initials: N
authors.lastname: Fazo
authors.forename: Preston A
authors.initials: PA
authors.lastname: Marx
authors.forename: Meredith
authors.initials: M
authors.lastname: Hunter
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Ramsburg
authors.forename: David
authors.initials: D
authors.lastname: Montefiori
authors.forename: Patricia
authors.initials: P
authors.lastname: Earl
authors.forename: Bernard
authors.initials: B
authors.lastname: Moss
authors.forename: John K
authors.initials: JK
authors.lastname: Rose
mesh_terms: D000818:Animals; D018791:CD4 Lymphocyte Count; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004279:DNA, Viral / Q000097:blood; D006678:HIV / Q000235:genetics / Q000276:immunology*; D015483:HIV Antibodies / Q000097:blood; D006801:Humans; D007117:Immunization, Secondary; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000821:virology; D008198:Lymph Nodes / Q000276:immunology / Q000821:virology; D008253:Macaca mulatta; D009500:Neutralization Tests; D011533:Proviruses / Q000235:genetics; D012367:RNA, Viral / Q000097:blood; D018449:SAIDS Vaccines / Q000235:genetics / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology*; D014616:Vaccinia virus / Q000235:genetics; D018116:Vesiculovirus / Q000235:genetics; D019562:Viral Load; D014766:Viremia
chemical_list: D004279:DNA, Viral; D015483:HIV Antibodies; D012367:RNA, Viral; D018449:SAIDS Vaccines