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Loss of reactivity of vaccine-induced CD4 T cells in immunized monkeys after SIV/HIV challenge

Puaux, Anne-Laurea; Delache, Benoitd; Marconi, Séverinea; Huerre, Michelc; Grand, Roger Led; Rivière, Yvesb; Michel, Marie-Louisea

Basic Science

Background: Immunization protocols involving priming with DNA and boosting with recombinant live virus vectors such as recombinant modified Vaccinia Ankara (rMVA) are considered as vaccine candidates against HIV. Such protocols improve the outcome of simian/human immunodeficiency virus (SHIV) pathogenic challenge in Rhesus monkeys.

Objectives: To investigate the fate of vaccine-induced T cells after a mucosal SHIV challenge.

Methods: We immunized Rhesus monkeys (Macaca mulatta) by DNA priming followed by rMVA boost. After intrarectal challenge with SHIV 89.6P, immunized animals demonstrated early control of viral replication and stable CD4 T-cell counts. We monitored T-cell responses by measuring IFN-γ secretion and proliferation.

Results: Immunization induced strong and sustained SHIV-specific CD4 and CD8 T-cell responses. CD8 T-cell responses were recalled during acute infection, whereas none of the vaccine-induced SHIV-specific CD4 T-cell responses were recalled. Moreover, most of the CD4 T-cell responses became undetectable in peripheral blood or lymph nodes even after in-vitro peptide stimulation. In contrast, we persistently detected CD4 T-cell responses specific for control recall antigens in infected animals.

Conclusion: SHIV 89.6P challenge results in a lack of reactivity of vaccine-induced SHIV-specific CD4 T cells. These results may have important implications in the AIDS vaccine field, especially for the evaluation of new vaccine candidates, both in preventive and therapeutic trials.

From the aINSERM U 370 Carcinogenèse Hépatique et Virologie Moléculaire

bLaboratoire d’Immunopathologie Virale, URA CNRS 1930, Département de Médecine Moléculaire

cUnité de Recherche et d’Expertise Histotechnologie et Pathologie, Institut Pasteur, Paris, France

dLaboratoire d’Immunopathologie Expérimentale, Service de Neurovirologie, DSV/DRM-CRSSA, Commissariat à l’Energie Atomique, Fontenay aux Roses, France.

Correspondence to Marie-Louise Michel, INSERM U 370 Carcinogenèse Hépatique et Virologie Moléculaire, Département de Médecine Moléculaire, Institut Pasteur, 28 Rue du Docteur Roux, 75724 Paris Cedex 15, France. Tel: +33 1 45 68 88 49; fax: +33 1 40 61 38 41; e-mail: maloum@pasteur.fr

© 2005 Lippincott Williams & Wilkins, Inc.