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


OBJECTIVE
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-gamma 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.


CONCLUSIONS
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.
Puaux
Anne-Laure
AL
INSERM U 370 Carcinogenèse Hépatique et Virologie Moléculaire, Département de Médecine Moléculaire, Institut Pasteur, Paris, France.
Delache
Benoit
B
Marconi
Séverine
S
Huerre
Michel
M
Le Grand
Roger
R
Rivière
Yves
Y
Michel
Marie-Louise
ML
D000818:Animals; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D049109:Cell Proliferation; D016207:Cytokines / Q000096:biosynthesis; D007156:Immunologic Memory; D018655:Lymphocyte Count; D008253:Macaca mulatta; D023421:Models, Animal; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000235:genetics; D019444:Vaccines, DNA / Q000008:administration & dosage*; D014614:Vaccines, Synthetic / Q000008:administration & dosage; D014615:Vaccinia; D014765:Viral Vaccines / Q000008:administration & dosage*; D014779:Virus Replication
D016207:Cytokines; D019444:Vaccines, DNA; D014614:Vaccines, Synthetic; D014765:Viral Vaccines