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


Autoria(s): Balla-Jhagjhoorsingh S.S.; Koopman G.; Mooij P.; Koornstra W.; McCormack S.; Weber J.; Pantaleo G.; Heeney J.L.
Data(s)

2004

Resumo

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.

Identificador

http://serval.unil.ch/?id=serval:BIB_9DC640B22EA7

isbn:0269-9370

pmid:15060431

doi:10.1097/01.aids.0000111431.91384.21

isiid:000221225500001

Idioma(s)

en

Fonte

AIDS, vol. 18, no. 6, pp. 837-848

Palavras-Chave #AIDS Vaccines/administration & dosage; Animals; Antibodies, Viral/blood; Antigens, CD45; Cytokines/blood; Epitopes/genetics; HIV-1; Immunologic Memory; L-Selectin; Pan troglodytes; Receptors, CCR7; Receptors, Chemokine; T-Lymphocytes, Cytotoxic/immunology; T-Lymphocytes, Helper-Inducer/immunology; Time Factors
Tipo

info:eu-repo/semantics/article

article