title: Long-term persistence of HIV-1 vaccine-induced CD4+CD45RA-CD62L-CCR7- memory T-helper cells.
abstract: OBJECTIVE
  To determine in chimpanzees if candidate HIV-1 subunit protein vaccines were capable of eliciting long-lasting T-cell memory responses in the absence of viral infection, and to determine the specific characteristics of these responses.
  
  
  METHODS
  A longitudinal study of cell-mediated immune responses induced in three chimpanzees following immunization with subunit envelope glycoproteins of either HIV-1 or herpes simplex virus (HSV)-2. Following these pre-clinical observations, four human volunteers who had been immunized 7 years previously with the same HIV-1 vaccine candidate donated blood for assessment of immune responses.
  
  
  METHODS
  Responses were monitored by protein and peptide based ELISpot assays, lymphocyte proliferation, and intracellular cytokine staining. Humoral responses were assessed by enzyme-linked immunosorbent assay and virus neutralization assays.
  
  
  RESULTS
  Although antigen (Ag)-specific CD4 T-cell responses persisted for at least 5 years in chimpanzees, CD8 T-cell responses were discordant and declined within 2 years. Detailed cellular analyses revealed that strong Th1 in addition to Th2 type responses were induced by AS2/gp120 and persisted, whereas CD8 T-cell memory declined in peripheral blood. The specificity of both Th and cytotoxic T-lymphocyte responses revealed that the majority of responses were directed to conserved epitopes. The remarkable persistence of Ag-specific CD4 T-cell memory was characterized as a population of the CD45RA-CD62L-CCR7- "effector phenotype" producing the cytokines IFNgamma, IL-2 and IL-4 upon epitope-specific recognition. Importantly, results in chimpanzees were confirmed in peripheral blood of one of four human volunteers studied more than 7 years after immunization.
  
  
  CONCLUSIONS
  These studies demonstrate that epitope-specific Th1 and Th2 cytokine-dependent Th responses can be induced and maintained for longer than 5 years by immunization with subunit proteins of HIV-1.
authors.affiliation: Department of Virology, Biomedical Primate Research Centre, 2280 GH Rijswijk, The Netherlands.
authors.forename: Sunita S
authors.initials: SS
authors.lastname: Balla-Jhagjhoorsingh
authors.forename: Gerrit
authors.initials: G
authors.lastname: Koopman
authors.forename: Petra
authors.initials: P
authors.lastname: Mooij
authors.forename: Wim
authors.initials: W
authors.lastname: Koornstra
authors.forename: Sheena
authors.initials: S
authors.lastname: McCormack
authors.forename: Jonathan
authors.initials: J
authors.lastname: Weber
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Pantaleo
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Heeney
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage*; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D016207:Cytokines / Q000097:blood; D000939:Epitopes / Q000235:genetics; D015497:HIV-1; D007156:Immunologic Memory; D019041:L-Selectin; D017493:Leukocyte Common Antigens; D002679:Pan troglodytes; D054400:Receptors, CCR7; D019707:Receptors, Chemokine; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D013997:Time Factors
chemical_list: D016915:AIDS Vaccines; D000914:Antibodies, Viral; C515370:CCR7 protein, human; D016207:Cytokines; D000939:Epitopes; D054400:Receptors, CCR7; D019707:Receptors, Chemokine; D019041:L-Selectin; D017493:Leukocyte Common Antigens