title: Cross-reactivity of anti-HIV-1 T cell immune responses among the major HIV-1 clades in HIV-1-positive individuals from 4 continents.
abstract: BACKGROUND
  The genetic diversity of human immunodeficiency virus type 1 (HIV-1) raises the question of whether vaccines that include a component to elicit antiviral T cell immunity based on a single viral genetic clade could provide cellular immune protection against divergent HIV-1 clades. Therefore, we quantified the cross-clade reactivity, among unvaccinated individuals, of anti-HIV-1 T cell responses to the infecting HIV-1 clade relative to other major circulating clades.
  
  
  METHODS
  Cellular immune responses to HIV-1 clades A, B, and C were compared by standardized interferon- gamma enzyme-linked immunospot assays among 250 unvaccinated individuals, infected with diverse HIV-1 clades, from Brazil, Malawi, South Africa, Thailand, and the United States. Cross-clade reactivity was evaluated by use of the ratio of responses to heterologous versus homologous (infecting) clades of HIV-1.
  
  
  RESULTS
  Cellular immune responses were predominantly focused on viral Gag and Nef proteins. Cross-clade reactivity of cellular immune responses to HIV-1 clade A, B, and C proteins was substantial for Nef proteins (ratio, 0.97 [95% confidence interval, 0.89-1.05]) and lower for Gag proteins (ratio, 0.67 [95% confidence interval, 0.62-0.73]). The difference in cross-clade reactivity to Nef and Gag proteins was significant (P<.0001).
  
  
  CONCLUSIONS
  Cross-clade reactivity of cellular immune responses can be substantial but varies by viral protein.
authors.affiliation: Merck Research Laboratories, West Point, Pennsylvania, USA. pcoplan@ipm-microbicides.org
authors.forename: Paul M
authors.initials: PM
authors.lastname: Coplan
authors.forename: Swati B
authors.initials: SB
authors.lastname: Gupta
authors.forename: Sheri A
authors.initials: SA
authors.lastname: Dubey
authors.forename: Punnee
authors.initials: P
authors.lastname: Pitisuttithum
authors.forename: Alex
authors.initials: A
authors.lastname: Nikas
authors.forename: Bernard
authors.initials: B
authors.lastname: Mbewe
authors.forename: Efthyia
authors.initials: E
authors.lastname: Vardas
authors.forename: Mauro
authors.initials: M
authors.lastname: Schechter
authors.forename: Esper G
authors.initials: EG
authors.lastname: Kallas
authors.forename: Dan C
authors.initials: DC
authors.lastname: Freed
authors.forename: Tong-Ming
authors.initials: TM
authors.lastname: Fu
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Mast
authors.forename: Pilaipan
authors.initials: P
authors.lastname: Puthavathana
authors.forename: James
authors.initials: J
authors.lastname: Kublin
authors.forename: Kelly
authors.initials: K
authors.lastname: Brown Collins
authors.forename: John
authors.initials: J
authors.lastname: Chisi
authors.forename: Richard
authors.initials: R
authors.lastname: Pendame
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Thaler
authors.forename: Glenda
authors.initials: G
authors.lastname: Gray
authors.forename: James
authors.initials: J
authors.lastname: Mcintyre
authors.forename: Walter L
authors.initials: WL
authors.lastname: Straus
authors.forename: Jon H
authors.initials: JH
authors.lastname: Condra
authors.forename: Devan V
authors.initials: DV
authors.lastname: Mehrotra
authors.forename: Harry A
authors.initials: HA
authors.lastname: Guess
authors.forename: Emilio A
authors.initials: EA
authors.lastname: Emini
authors.forename: John W
authors.initials: JW
authors.lastname: Shiver
mesh_terms: D000328:Adult; D016384:Consensus Sequence; D003429:Cross Reactions; D005260:Female; D015693:Gene Products, nef / Q000737:chemistry / Q000235:genetics; D005843:Geography; D006679:HIV Seropositivity / Q000276:immunology*; D015497:HIV-1 / Q000145:classification / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology*; D054311:nef Gene Products, Human Immunodeficiency Virus
chemical_list: D015693:Gene Products, nef; D054311:nef Gene Products, Human Immunodeficiency Virus