title: Delay of simian human immunodeficiency virus infection and control of viral replication in vaccinated macaques challenged in the presence of a topical microbicide.
abstract: OBJECTIVE
  Development of an effective vaccine or topical compound to prevent HIV transmission remains a major goal for control of the AIDS pandemic. Using a nonhuman primate model of heterosexual HIV-1 transmission, we tested whether a topical microbicide that reduces viral infectivity can potentiate the efficacy of a T-cell-based HIV vaccine.
  
  
  METHODS
  A DNA prime and rAd5 virus boost vaccination strategy was employed, and a topical microbicide against the HIV nucleocapsid protein was used. To rigorously test the combination hypothesis, the vaccine constructs contained only two transgenes and the topical microbicide inhibitor was used at a suboptimal dose. Vaccinees were exposed in the absence and presence of the topical microbicide to repeated vaginal R5 simian human immunodeficiency virus (SHIV)(SF162P3) challenge at an escalating dose to more closely mimic high-risk exposure of women to HIV.
  
  
  METHODS
  Infection status was determined by PCR. Antiviral immune responses were evaluated by gp120 ELISA and intracellular cytokine staining.
  
  
  RESULTS
  A significant delay in SHIV acquisition (log-rank test; P = 0.0416) was seen only in vaccinated macaques that were repeatedly challenged in the presence of the topical microbicide. Peak acute viremia was lower (Mann-Whitney test; P = 0.0387) and viral burden was also reduced (Mann-Whitney test; P = 0.0252) in the combination-treated animals.
  
  
  CONCLUSIONS
  The combined use of a topical microbicide to lower the initial viral seeding/spread and a T-cell-based vaccine to immunologically contain the early virological events of mucosal transmission holds promise as a preventive approach to control the spread of the AIDS epidemic.
authors.affiliation: Aaron Diamond AIDS Research Center, New York, New York 10016, USA. cmayer@adarc.org
authors.forename: Cecilia
authors.initials: C
authors.lastname: Cheng-Mayer
authors.forename: Yaoxing
authors.initials: Y
authors.lastname: Huang
authors.forename: Agegnehu
authors.initials: A
authors.lastname: Gettie
authors.forename: Lily
authors.initials: L
authors.lastname: Tsai
authors.forename: Wuze
authors.initials: W
authors.lastname: Ren
authors.forename: Madina
authors.initials: M
authors.lastname: Shakirzyanova
authors.forename: Silvana T
authors.initials: ST
authors.lastname: Sina
authors.forename: Nataliya
authors.initials: N
authors.lastname: Trunova
authors.forename: James
authors.initials: J
authors.lastname: Blanchard
authors.forename: Lisa M Miller
authors.initials: LM
authors.lastname: Jenkins
authors.forename: Yungtai
authors.initials: Y
authors.lastname: Lo
authors.forename: Marco L
authors.initials: ML
authors.lastname: Schito
authors.forename: Ettore
authors.initials: E
authors.lastname: Appella
mesh_terms: D000818:Animals; D000891:Anti-Infective Agents, Local / Q000494:pharmacology*; D000914:Antibodies, Viral / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D015497:HIV-1; D008253:Macaca mulatta; D016097:Simian Acquired Immunodeficiency Syndrome / Q000188:drug therapy / Q000276:immunology* / Q000517:prevention & control; D015302:Simian Immunodeficiency Virus / Q000187:drug effects / Q000276:immunology*; D014765:Viral Vaccines / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects / Q000276:immunology*
chemical_list: D000891:Anti-Infective Agents, Local; D000914:Antibodies, Viral; D014765:Viral Vaccines