title: T-cell immune responses against Env from CRF12_BF and subtype B HIV-1 show high clade-specificity that can be overridden by multiclade immunizations.
abstract: BACKGROUND
  The extreme genetic diversity of the human immunodeficiency virus type 1 (HIV-1) poses a daunting challenge to the generation of an effective AIDS vaccine. In Argentina, the epidemic is characterized by the high prevalence of infections caused by subtype B and BF variants. The aim of this study was to characterize in mice the immunogenic and antigenic properties of the Env protein from CRF12_BF in comparison with clade B, employing prime-boost schemes with the combination of recombinant DNA and vaccinia virus (VV) vectors.
  
  
  RESULTS
  As determined by ELISPOT from splenocytes of animals immunized with either EnvBF or EnvB antigens, the majority of the cellular responses to Env were found to be clade-specific. A detailed peptide mapping of the responses reveal that when there is cross-reactivity, there are no amino acid changes in the peptide sequence or were minimal and located at the peptide ends. In those cases, analysis of T cell polifunctionality and affinity indicated no differences with respect to the cellular responses found against the original homologous sequence. Significantly, application of a mixed immunization combining both clades (B and BF) induced a broader cellular response, in which the majority of the peptides targeted after the single clade vaccinations generated a positive response. In this group we could also find significant cellular and humoral responses against the whole gp120 protein from subtype B.
  
  
  CONCLUSIONS
  This work has characterized for the first time the immunogenic peptides of certain EnvBF regions, involved in T cell responses. It provides evidence that to improve immune responses to HIV there is a need to combine Env antigens from different clades, highlighting the convenience of the inclusion of BF antigens in future vaccines for geographic regions where these HIV variants circulate.
authors.affiliation: Centro Nacional de Referencia para el SIDA, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: Daniela C
authors.initials: DC
authors.lastname: Mónaco
authors.forename: Ana M
authors.initials: AM
authors.lastname: Rodríguez
authors.forename: María F
authors.initials: MF
authors.lastname: Pascutti
authors.forename: Mauricio
authors.initials: M
authors.lastname: Carobene
authors.forename: Juliana
authors.initials: J
authors.lastname: Falivene
authors.forename: Alejandro
authors.initials: A
authors.lastname: Gómez
authors.forename: Cynthia
authors.initials: C
authors.lastname: Maeto
authors.forename: Gabriela
authors.initials: G
authors.lastname: Turk
authors.forename: José L
authors.initials: JL
authors.lastname: Nájera
authors.forename: Mariano
authors.initials: M
authors.lastname: Esteban
authors.forename: M Magdalena
authors.initials: MM
authors.lastname: Gherardi
mesh_terms: D016915:AIDS Vaccines / Q000627:therapeutic use; D000595:Amino Acid Sequence; D000818:Animals; D041702:BALB 3T3 Cells; D002478:Cells, Cultured; D005260:Female; D015488:HIV Antigens / Q000235:genetics / Q000276:immunology; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control; D015497:HIV-1 / Q000145:classification* / Q000235:genetics / Q000276:immunology*; D006367:HeLa Cells; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology*; D007114:Immunization / Q000379:methods*; D051379:Mice; D008807:Mice, Inbred BALB C; D008954:Models, Biological; D008969:Molecular Sequence Data; D037182:T-Cell Antigen Receptor Specificity / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000502:physiology; D054299:env Gene Products, Human Immunodeficiency Virus / Q000737:chemistry / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; D015488:HIV Antigens; D054299:env Gene Products, Human Immunodeficiency Virus