Improved protection against simian immunodeficiency virus mucosal challenge in macaques primed with a DNA vaccine and boosted with the recombinant modified vaccinia virus Ankara and recombinant Semliki Forest virus.
Using the experimental infection of cynomolgus macaques with simian immunodeficiency virus (SIV) as a model of human immunodeficiency virus infection in humans, we studied the immunogenicity and protective efficacy of a vaccine strategy combining DNA, the modified recombinant vaccinia virus strain Ankara (MVA) and Semliki Forest virus (SFV) expressing gag, pol, env, tat, rev and nef from SIV. Although this immunization strategy induced moderate immune responses, the control of pathogenic SIVmac251 infection following mucosal challenge was clearly improved by vaccination. The viral load in vaccinated animals was reduced by 2 logs during the acute phase of infection and, in five of the six macaques, viral load fell below the detection limit at set point. No correlates of immune protection were identified, but SIV-specific T-cell responses were detected earlier in vaccinated animals than in controls. These results highlight the power of live attenuated virus vectors for vaccination strategies.
Martinon
Frédéric
F
CEA, Service d'Immuno-Virologie, DSV, iMETI, 18 route du Panorama, Fontenay Aux Roses, France. frederic.martinon@cea.fr
Brochard
Patricia
P
Ripaux
Maryline
M
Delache
Benoît
B
Aurégan
Gwenaelle
G
Vaslin
Bruno
B
Le Grand
Roger
R
D000818:Animals; D005814:Genes, Viral; D005822:Genetic Vectors / Q000276:immunology; D007117:Immunization, Secondary; D007273:Injections, Intramuscular; D007279:Injections, Subcutaneous; D008213:Lymphocyte Activation; D008252:Macaca fascicularis; D008297:Male; D009092:Mucous Membrane; D018449:SAIDS Vaccines / Q000008:administration & dosage / Q000276:immunology; D012672:Semliki forest virus / Q000235:genetics* / Q000276:immunology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000235:genetics* / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology; D019562:Viral Load; D014765:Viral Vaccines / Q000008:administration & dosage* / Q000276:immunology
D018449:SAIDS Vaccines; D019444:Vaccines, DNA; D014614:Vaccines, Synthetic; D014765:Viral Vaccines