Recombinant vector-induced HIV/SIV-specific CD4+ T lymphocyte responses in rhesus monkeys.
The recently reported modest success of the RV144 Thai trial vaccine regimen in preventing HIV-1 acquisition has focused interest on the potential contribution to that protection of vaccine-elicited CD4(+) T cell responses. We evaluated the induction of virus-specific CD4(+) T cell responses in rhesus monkeys using a series of diverse vaccine vectors. We assessed both the magnitudes and functional profiles of the antigen-specific CD4(+) T cells by measuring cytokine production, memory differentiation, and the expression of mucosal homing molecules. We found that DNA prime/recombinant MVA boost immunizations induced particularly high-frequency virus-specific CD4(+) T cell responses with polyfunctional repertoires, and these responses were partially preserved following SHIV-89.6P challenge. The majority of the vaccine-elicited CD4(+) T cells were CD28(+) memory T cells that expressed low levels of beta7. Neither the magnitudes nor the functional profiles of the virus-specific CD4(+) T cells generated by vaccination were associated with a preservation of CD4(+) T cells or control of viral replication following SHIV-89.6P challenge. Interestingly, monkeys primed with recombinant Ad5 immunogens showed a dramatic expansion of both the magnitude and polyfunctionality of the vaccine-elicited CD4(+) T cell responses following envelope protein boost. These results demonstrate that vaccine strategies that include recombinant MVA or recombinant Ad5 vectors can elicit robust CD4(+) T cell responses.
Sun
Yue
Y
Division of Viral Pathogenesis, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA.
Santra
Sampa
S
Buzby
Adam P
AP
Mascola
John R
JR
Nabel
Gary J
GJ
Letvin
Norman L
NL
D016915:AIDS Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D000256:Adenoviridae / Q000235:genetics / Q000276:immunology; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology*; D016207:Cytokines / Q000096:biosynthesis; D005822:Genetic Vectors; D015497:HIV-1 / Q000235:genetics* / Q000276:immunology* / Q000502:physiology; D006801:Humans; D018928:Immunity, Mucosal; D007117:Immunization, Secondary; D007156:Immunologic Memory; D008253:Macaca mulatta / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000235:genetics* / Q000276:immunology* / Q000502:physiology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014779:Virus Replication
D016915:AIDS Vaccines; D016207:Cytokines; D014614:Vaccines, Synthetic