title: T-cell-mediated protective efficacy of a systemic vaccine approach in cynomolgus monkeys after SIV mucosal challenge.
abstract: The immunogenicity and the protective efficacy of a new polyvalent triple vector (DNA/SFV/MVA) based vaccine against mucosal challenge with pathogenic SIVmac251 were investigated. Cynomolgus monkeys (Macaca fascicularis) were primed intradermally with DNA, boosted twice subcutaneously with recombinant Semliki Forest virus (rSFV) and finally intramuscularly with recombinant Modified Vaccinia Virus Ankara strain (rMVA). Both DNA and recombinant viral vectors expressed SIV proteins (Gag, Pol, Tat, Rev, Nef and Env). The vaccinated monkeys developed T helper proliferative responses to viral antigens after the second immunization while interferon (IFN)-gamma enzyme-linked immunosorbent spot-forming cell assay (ELISPOT) specific responses appeared only after the last boost with rMVA. Upon intrarectal challenge with pathogenic SIVmac251, three of four vaccinated monkeys were either fully protected or exhibited a dramatic reduction of virus replication up to undetectable level. A major contribution to this protective effect appeared to be the anamnestic T-cell IFN-gamma ELISPOT responses to vaccine antigens (Gag, Rev, Tat, Nef) that mirrored the viral clearance. These results underline the efficacy of a multiprotein approach in combination with a triple vector system of antigen delivery.
authors.affiliation: Laboratory of Virology, Istituto Superiore Sanità, Rome, Italy.
authors.forename: Zuleika
authors.initials: Z
authors.lastname: Michelini
authors.forename: Donatella R M
authors.initials: DR
authors.lastname: Negri
authors.forename: Silvia
authors.initials: S
authors.lastname: Baroncelli
authors.forename: Stefania
authors.initials: S
authors.lastname: Catone
authors.forename: Antonella
authors.initials: A
authors.lastname: Comini
authors.forename: Maria T
authors.initials: MT
authors.lastname: Maggiorella
authors.forename: Leonardo
authors.initials: L
authors.lastname: Sernicola
authors.forename: Federica
authors.initials: F
authors.lastname: Crostarosa
authors.forename: Roberto
authors.initials: R
authors.lastname: Belli
authors.forename: Maria G
authors.initials: MG
authors.lastname: Mancini
authors.forename: Stefania
authors.initials: S
authors.lastname: Farcomeni
authors.forename: Zahra
authors.initials: Z
authors.lastname: Fagrouch
authors.forename: Massimo
authors.initials: M
authors.lastname: Ciccozzi
authors.forename: Claudia
authors.initials: C
authors.lastname: Rovetto
authors.forename: Peter
authors.initials: P
authors.lastname: Liljestrom
authors.forename: Stephen
authors.initials: S
authors.lastname: Norley
authors.forename: Jonathan
authors.initials: J
authors.lastname: Heeney
authors.forename: Fausto
authors.initials: F
authors.lastname: Titti
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis / Q000097:blood; D000956:Antigens, Viral / Q000276:immunology; D049109:Cell Proliferation; D004797:Enzyme-Linked Immunosorbent Assay; D007371:Interferon-gamma / Q000276:immunology; D008252:Macaca fascicularis / Q000276:immunology* / Q000821:virology*; D008297:Male; D009500:Neutralization Tests; D012367:RNA, Viral / Q000737:chemistry / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018449:SAIDS Vaccines / Q000276:immunology*; D012672:Semliki forest virus / Q000276:immunology; D016097:Simian Acquired Immunodeficiency Syndrome / Q000097:blood / Q000276:immunology* / Q000517:prevention & control / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D014611:Vaccination / Q000379:methods / Q000662:veterinary*; D019444:Vaccines, DNA / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology; D014616:Vaccinia virus / Q000276:immunology; D019562:Viral Load
chemical_list: D000914:Antibodies, Viral; D000956:Antigens, Viral; D012367:RNA, Viral; D018449:SAIDS Vaccines; D019444:Vaccines, DNA; D014614:Vaccines, Synthetic; D007371:Interferon-gamma