title: Prime-boost regimens with adjuvanted synthetic long peptides elicit T cells and antibodies to conserved regions of HIV-1 in macaques.
abstract: OBJECTIVE
  Administration of synthetic long peptides (SLPs) derived from human papillomavirus to cervical cancer patients resulted in clinical benefit correlated with expansions of tumour-specific T cells. Because vaginal mucosa is an important port of entry for HIV-1, we have explored SLP for HIV-1 vaccination. Using immunogen HIVconsv derived from the conserved regions of HIV-1, we previously showed in rhesus macaques that SLP.HIVconsv delivered as a boost increased the breath of T-cell specificities elicited by single-gene vaccines. Here, we compared and characterized the use of electroporated pSG2.HIVconsv DNA (D) and imiquimod/montanide-adjuvanted SLP.HIVconsv (S) as priming vaccines for boosting with attenuated chimpanzee adenovirus ChAdV63.HIVconsv (C) and modified vaccinia virus Ankara MVA.HIVconsv (M).
  
  
  METHODS
  Prime-boost regimens of DDDCMS, DSSCMS and SSSCMS in rhesus macaques.
  
  
  METHODS
  Animals' blood was analysed regularly throughout the vaccination for HIV-1-specific T-cell and antibody responses.
  
  
  RESULTS
  We found that electroporation spares DNA dose, both SLP.HIVconsv and pSG2.HIVconsv DNA primed weakly HIVconsv-specific T cells, regimen DDDCM induced the highest frequencies of oligofunctional, proliferating CD4(+) and CD8(+) T cells, and a subsequent SLP.HIVconsv boost expanded primarily CD4(+) cells. DSS was the most efficient regimen inducing antibodies binding to regions of trimeric HIV-1 Env, which are highly conserved among the four major global clades, although no unequivocal neutralizing activity was detected.
  
  
  CONCLUSIONS
  The present results encourage evaluation of the SLP.HIVconsv vaccine modality in human volunteers along the currently trialled pSG2.HIVconsv DNA, ChAdV63.HIVconsv and MVA.HIVconsv vaccines. These results are discussed in the context of the RV144 trial outcome.
authors.affiliation: MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, The John Radcliffe, UK.
authors.forename: Maximillian
authors.initials: M
authors.lastname: Rosario
authors.forename: Nicola
authors.initials: N
authors.lastname: Borthwick
authors.forename: Guillaume B
authors.initials: GB
authors.lastname: Stewart-Jones
authors.forename: Alice
authors.initials: A
authors.lastname: Mbewe-Mvula
authors.forename: Anne
authors.initials: A
authors.lastname: Bridgeman
authors.forename: Stefano
authors.initials: S
authors.lastname: Colloca
authors.forename: David
authors.initials: D
authors.lastname: Montefiori
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: McMichael
authors.forename: Alfredo
authors.initials: A
authors.lastname: Nicosia
authors.forename: Esther D
authors.initials: ED
authors.lastname: Quakkelaar
authors.forename: Jan W
authors.initials: JW
authors.lastname: Drijfhout
authors.forename: Cornelis J M
authors.initials: CJ
authors.lastname: Melief
authors.forename: Tomáš
authors.initials: T
authors.lastname: Hanke
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology / Q000494:pharmacology*; D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects*; D004279:DNA, Viral / Q000276:immunology; D018274:Electroporation; D015483:HIV Antibodies / Q000276:immunology*; D015497:HIV-1 / Q000187:drug effects*; D007117:Immunization, Secondary / Q000379:methods; D008213:Lymphocyte Activation; D008253:Macaca mulatta; D014614:Vaccines, Synthetic / Q000276:immunology / Q000494:pharmacology*; D014616:Vaccinia virus / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; D004279:DNA, Viral; D015483:HIV Antibodies; D014614:Vaccines, Synthetic