title: Optimizing parallel induction of HIV type 1-specific antibody and T-cell responses by multicomponent subunit vaccines.
abstract: OBJECTIVE
  Protection against HIV type 1 (HIV-1) infection/AIDS will likely require concerted actions of protective CD8(+) killer T cells and protective antibodies. The challenges in inducing such effectors by active immunization are such that the T-cell and antibody vaccine components require separate development. Here, a rational attempt is taken to combine two separately optimized heterologous regimens into a single T-cell-inducing and antibody-inducing vaccination schedule with minimal induction of unprotective Env-specific T cells.
  
  
  METHODS
  Clade A BG505 Env-derived uncleaved gp140 (BG505u) and conserved region tHIVc immunogens were utilized and presented to the immune system using non-replicating simian (chimpanzee) adenovirus ChAdV-63 (C) and poxvirus-modified vaccinia virus Ankara MVA (M). In addition, purified BG505 gp120 (P) was used for antibody induction.
  
  
  METHODS
  BALB/c mice were vaccinated to elicit Env antibodies alone using ChAdV63.BG505u. MVA.BG505u and BG505 gp120 in regimens CMP, CPP and PPP, and in combination with the ChAdV63.tHIVc and MVA.tHIVc components in regimens CMP+CMM, CPP+CMM and PPP+CMM. Antibody and T-cell responses to BG505 Env and conserved regions of the HIV-1 proteome were determined.
  
  
  RESULTS
  Although all three regimens delivering BG505 Env induced similar levels of antibodies, BG505-specific T cells were induced in the CMP>CPP>PPP hierarchy, which was maintained during coinduction of tHIVc-specific T cells. Adjuvanted BG505 PPP decreased induction of tHIVc-specific T cells and tHIVc T-cell induction decreased induction of BG505 Ab. As expected, the antibodies that were induced neutralized tier 1 HIV-1 strains.
  
  
  CONCLUSIONS
  These results inform designs of initial human studies combining separately optimized T-cell and B-cell HIV-1 vaccines into a single regimen.
authors.affiliation: aThe Jenner Institute, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford, UK bVaccine Design and Development Lab, International AIDS Vaccine Initiative, Brooklyn, New York cDuke Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: Genevieve
authors.initials: G
authors.lastname: Clutton
authors.forename: Alexei
authors.initials: A
authors.lastname: Carpov
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Parks
authors.forename: Hansi J
authors.initials: HJ
authors.lastname: Dean
authors.forename: David C
authors.initials: DC
authors.lastname: Montefiori
authors.forename: Tomáš
authors.initials: T
authors.lastname: Hanke
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D004337:Drug Carriers; D005260:Female; D015497:HIV-1 / Q000276:immunology*; D008807:Mice, Inbred BALB C; D013601:T-Lymphocytes / Q000276:immunology*; D016896:Treatment Outcome; D014611:Vaccination / Q000379:methods*; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014616:Vaccinia virus / Q000235:genetics; D054299:env Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification
chemical_list: D016915:AIDS Vaccines; D004337:Drug Carriers; D022223:Vaccines, Subunit; D054299:env Gene Products, Human Immunodeficiency Virus