title: Protective efficacy of a multicomponent vector vaccine in cynomolgus monkeys after intrarectal simian immunodeficiency virus challenge.
abstract: 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.
authors.affiliation: Laboratory of Virology, Istituto Superiore di Sanità, Viale R. Elena 299, 00161 Rome, Italy.
authors.forename: Donatella R M
authors.initials: DRM
authors.lastname: Negri
authors.affiliation: Laboratory of Virology, Istituto Superiore di Sanità, Viale R. Elena 299, 00161 Rome, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Baroncelli
authors.affiliation: Laboratory of Virology, Istituto Superiore di Sanità, Viale R. Elena 299, 00161 Rome, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Catone
authors.affiliation: Laboratory of Virology, Istituto Superiore di Sanità, Viale R. Elena 299, 00161 Rome, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Comini
authors.affiliation: Laboratory of Virology, Istituto Superiore di Sanità, Viale R. Elena 299, 00161 Rome, Italy.
authors.forename: Zuleika
authors.initials: Z
authors.lastname: Michelini
authors.affiliation: Laboratory of Virology, Istituto Superiore di Sanità, Viale R. Elena 299, 00161 Rome, Italy.
authors.forename: Maria T
authors.initials: MT
authors.lastname: Maggiorella
authors.affiliation: Laboratory of Virology, Istituto Superiore di Sanità, Viale R. Elena 299, 00161 Rome, Italy.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Sernicola
authors.affiliation: Laboratory of Virology, Istituto Superiore di Sanità, Viale R. Elena 299, 00161 Rome, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Crostarosa
authors.affiliation: Laboratory of Virology, Istituto Superiore di Sanità, Viale R. Elena 299, 00161 Rome, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Belli
authors.affiliation: Laboratory of Virology, Istituto Superiore di Sanità, Viale R. Elena 299, 00161 Rome, Italy.
authors.forename: Maria G
authors.initials: MG
authors.lastname: Mancini
authors.affiliation: Laboratory of Virology, Istituto Superiore di Sanità, Viale R. Elena 299, 00161 Rome, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Farcomeni
authors.affiliation: Department of Virology, Biomedical Primate Research Center, PO Box 3306, 2280 GH Rijswijk, The Netherlands.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Fagrouch
authors.affiliation: Laboratory of Epidemiology and Biostatistics, Istituto Superiore di Sanità, Viale R. Elena 299, 00161 Rome, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Ciccozzi
authors.affiliation: Laboratory of Epidemiology and Biostatistics, Istituto Superiore di Sanità, Viale R. Elena 299, 00161 Rome, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Boros
authors.affiliation: Microbiology and Tumor-Biology Center, Karolinska Institute, Box 280, S-17177 Stockholm, Sweden.
authors.forename: Peter
authors.initials: P
authors.lastname: Liljestrom
authors.affiliation: AIDS Immunopathogenesis and Vaccine Development, Robert Koch Institute, 13353 Berlin, Germany.
authors.forename: Stephen
authors.initials: S
authors.lastname: Norley
authors.affiliation: Department of Virology, Biomedical Primate Research Center, PO Box 3306, 2280 GH Rijswijk, The Netherlands.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Heeney
authors.affiliation: Laboratory of Virology, Istituto Superiore di Sanità, Viale R. Elena 299, 00161 Rome, Italy.
authors.forename: Fausto
authors.initials: F
authors.lastname: Titti
mesh_terms: 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*
chemical_list: D016915:AIDS Vaccines; D000956:Antigens, Viral; D014614:Vaccines, Synthetic; D014765:Viral Vaccines