T-cell-mediated protective efficacy of a systemic vaccine approach in cynomolgus monkeys after SIV mucosal challenge.
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.
Michelini
Zuleika
Z
Laboratory of Virology, Istituto Superiore Sanità, Rome, Italy.
Negri
Donatella R M
DR
Baroncelli
Silvia
S
Catone
Stefania
S
Comini
Antonella
A
Maggiorella
Maria T
MT
Sernicola
Leonardo
L
Crostarosa
Federica
F
Belli
Roberto
R
Mancini
Maria G
MG
Farcomeni
Stefania
S
Fagrouch
Zahra
Z
Ciccozzi
Massimo
M
Rovetto
Claudia
C
Liljestrom
Peter
P
Norley
Stephen
S
Heeney
Jonathan
J
Titti
Fausto
F
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
D000914:Antibodies, Viral; D000956:Antigens, Viral; D012367:RNA, Viral; D018449:SAIDS Vaccines; D019444:Vaccines, DNA; D014614:Vaccines, Synthetic; D007371:Interferon-gamma