Long-term persistence of HIV-1 vaccine-induced CD4+CD45RA-CD62L-CCR7- memory T-helper cells

AIDS. 2004 Apr 9;18(6):837-48. doi: 10.1097/00002030-200404090-00001.

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.

Design: 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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AIDS Vaccines / administration & dosage*
  • Animals
  • Antibodies, Viral / blood
  • Cytokines / blood
  • Epitopes / genetics
  • HIV-1*
  • Immunologic Memory
  • L-Selectin
  • Leukocyte Common Antigens
  • Pan troglodytes
  • Receptors, CCR7
  • Receptors, Chemokine
  • T-Lymphocytes, Cytotoxic / immunology
  • T-Lymphocytes, Helper-Inducer / immunology*
  • Time Factors

Substances

  • AIDS Vaccines
  • Antibodies, Viral
  • CCR7 protein, human
  • Cytokines
  • Epitopes
  • Receptors, CCR7
  • Receptors, Chemokine
  • L-Selectin
  • Leukocyte Common Antigens