Protective efficacy of a multicomponent vector vaccine in cynomolgus monkeys after intrarectal simian immunodeficiency virus challenge.
We investigated the protective efficacy of a systemic triple vector (DNA/rSFV/rMVA)-based vaccine against mucosal challenge with pathogenic simian immunodeficiency virus (SIV) in cynomolgus monkeys. Animals were immunized at week 0 with DNA (intradermally), at weeks 8 and 16 with recombinant Semliki Forest virus (rSFV, subcutaneously) and finally, at week 24, with recombinant modified vaccinia virus Ankara strain (rMVA, intramuscularly). Both DNA and recombinant viral vectors expressed a wide range of SIV proteins (Gag, Pol, Tat, Rev, Env and Nef). This immunization strategy elicited cell-mediated rather than humoral responses that were especially increased following the last boost. Upon intrarectal challenge with pathogenic SIVmac251, three of the four vaccinated monkeys dramatically abrogated virus load to undetectable levels up to 41 weeks after challenge. A major contribution to this vaccine effect appeared to be the T-cell-mediated immune response to vaccine antigens (Gag, Rev, Tat, Nef) seen in the early phase of infection in three of the four vaccinated monkeys. Indeed, the frequency of T-cells producing antigen-induced IFN-gamma mirrored virus clearance in the vaccinated and protected monkeys. These results, reminiscent of the efficacy of live attenuated virus vaccines, suggest that vaccination with a combination of many viral antigens can induce a robust and stable vaccine-induced immunity able to abrogate virus replication.
Negri
Donatella R M
DRM
Laboratory of Virology, Istituto Superiore di Sanità, Viale R. Elena 299, 00161 Rome, Italy.
Baroncelli
Silvia
S
Laboratory of Virology, Istituto Superiore di Sanità, Viale R. Elena 299, 00161 Rome, Italy.
Catone
Stefania
S
Laboratory of Virology, Istituto Superiore di Sanità, Viale R. Elena 299, 00161 Rome, Italy.
Comini
Antonella
A
Laboratory of Virology, Istituto Superiore di Sanità, Viale R. Elena 299, 00161 Rome, Italy.
Michelini
Zuleika
Z
Laboratory of Virology, Istituto Superiore di Sanità, Viale R. Elena 299, 00161 Rome, Italy.
Maggiorella
Maria T
MT
Laboratory of Virology, Istituto Superiore di Sanità, Viale R. Elena 299, 00161 Rome, Italy.
Sernicola
Leonardo
L
Laboratory of Virology, Istituto Superiore di Sanità, Viale R. Elena 299, 00161 Rome, Italy.
Crostarosa
Federica
F
Laboratory of Virology, Istituto Superiore di Sanità, Viale R. Elena 299, 00161 Rome, Italy.
Belli
Roberto
R
Laboratory of Virology, Istituto Superiore di Sanità, Viale R. Elena 299, 00161 Rome, Italy.
Mancini
Maria G
MG
Laboratory of Virology, Istituto Superiore di Sanità, Viale R. Elena 299, 00161 Rome, Italy.
Farcomeni
Stefania
S
Laboratory of Virology, Istituto Superiore di Sanità, Viale R. Elena 299, 00161 Rome, Italy.
Fagrouch
Zahra
Z
Department of Virology, Biomedical Primate Research Center, PO Box 3306, 2280 GH Rijswijk, The Netherlands.
Ciccozzi
Massimo
M
Laboratory of Epidemiology and Biostatistics, Istituto Superiore di Sanità, Viale R. Elena 299, 00161 Rome, Italy.
Boros
Stefano
S
Laboratory of Epidemiology and Biostatistics, Istituto Superiore di Sanità, Viale R. Elena 299, 00161 Rome, Italy.
Liljestrom
Peter
P
Microbiology and Tumor-Biology Center, Karolinska Institute, Box 280, S-17177 Stockholm, Sweden.
Norley
Stephen
S
AIDS Immunopathogenesis and Vaccine Development, Robert Koch Institute, 13353 Berlin, Germany.
Heeney
Jonathan
J
Department of Virology, Biomedical Primate Research Center, PO Box 3306, 2280 GH Rijswijk, The Netherlands.
Titti
Fausto
F
Laboratory of Virology, Istituto Superiore di Sanità, Viale R. Elena 299, 00161 Rome, Italy.
D016915:AIDS Vaccines / Q000008:administration & dosage; D000818:Animals; D000956:Antigens, Viral / Q000276:immunology; D004195:Disease Models, Animal; D005822:Genetic Vectors / Q000008:administration & dosage*; D007115:Immunization Schedule; D008213:Lymphocyte Activation; D008252:Macaca fascicularis; D008297:Male; D011995:Recombination, Genetic; D012672:Semliki forest virus / Q000235:genetics / Q000276:immunology; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000517:prevention & control*; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000008:administration & dosage; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology; D014765:Viral Vaccines / Q000008:administration & dosage*
D016915:AIDS Vaccines; D000956:Antigens, Viral; D014614:Vaccines, Synthetic; D014765:Viral Vaccines