Role of complement and antibodies in controlling infection with pathogenic simian immunodeficiency virus (SIV) in macaques vaccinated with replication-deficient viral vectors.
BACKGROUND
We investigated the interplay between complement and antibodies upon priming with single-cycle replicating viral vectors (SCIV) encoding SIV antigens combined with Adeno5-SIV or SCIV pseudotyped with murine leukemia virus envelope boosting strategies. The vaccine was applied via spray-immunization to the tonsils of rhesus macaques and compared with systemic regimens.


RESULTS
Independent of the application regimen or route, viral loads were significantly reduced after challenge with SIVmac239 (p < 0.03) compared to controls. Considerable amounts of neutralizing antibodies were induced in systemic immunized monkeys. Most of the sera harvested during peak viremia exhibited a trend with an inverse correlation between complement C3-deposition on viral particles and plasma viral load within the different vaccination groups. In contrast, the amount of the observed complement-mediated lysis did not correlate with the reduction of SIV titres.


CONCLUSIONS
The heterologous prime-boost strategy with replication-deficient viral vectors administered exclusively via the tonsils did not induce any neutralizing antibodies before challenge. However, after challenge, comparable SIV-specific humoral immune responses were observed in all vaccinated animals. Immunization with single cycle immunodeficiency viruses mounts humoral immune responses comparable to live-attenuated immunodeficiency virus vaccines.
Falkensammer
Barbara
B
Department of Hygiene, Microbiology and Social Medicine, Innsbruck Medical University, 6020 Innsbruck, Austria. barbara.falkensammer@i-med.ac.at
Rubner
Barbara
B
Hiltgartner
Alexander
A
Wilflingseder
Doris
D
Stahl Hennig
Christiane
C
Kuate
Seraphin
S
Uberla
Klaus
K
Norley
Stephen
S
Strasak
Alexander
A
Racz
Paul
P
Stoiber
Heribert
H
D000260:Adenoviruses, Human / Q000235:genetics; D000336:Aerosols; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology*; D003165:Complement System Proteins / Q000276:immunology*; D005822:Genetic Vectors; D009052:Leukemia Virus, Murine / Q000235:genetics; D008253:Macaca mulatta; D009500:Neutralization Tests; D014066:Palatine Tonsil / Q000821:virology; D018449:SAIDS Vaccines / Q000276:immunology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000517:prevention & control*; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology*; D019562:Viral Load
D000336:Aerosols; D000914:Antibodies, Viral; D018449:SAIDS Vaccines; D003165:Complement System Proteins