Evaluation of recombinant Kunjin replicon SIV vaccines for protective efficacy in macaques.
Persistent gag-specific T cell immunity would be a useful component of an effective HIV vaccine. The Flavivirus Kunjin replicon was previously engineered to persistently express HIV gag and was shown to induce protective responses in mice. We evaluated Kunjin replicon virus-like-particles expressing SIVgag-pol in pigtail macaques. Kunjin-specific antibodies were induced, but no SIV-specific T cell immunity were detected. Following SIVmac251 challenge, there was no difference in SIV viremia or retention of CD4 T cells between Kunjin-SIVgag-pol vaccine immunized animals and controls. An amnestic SIV gag-specific CD8 T cell response associated with control of viremia was observed in 1 of 6 immunized animals. Refinements of this vector system and optimization of the immunization doses, routes, and schedules are required prior to clinical trials.
Kent
Stephen J
SJ
Department of Microbiology and Immunology, University of Melbourne, 3010, Australia. skent@unimelb.edu.au
De Rose
Robert
R
Mokhonov
Vlad V
VV
Mokhonova
Ekaterina I
EI
Fernandez
Caroline S
CS
Alcantara
Sheilajen
S
Rollman
Erik
E
Mason
Rosemarie D
RD
Loh
Liyen
L
Peut
Viv
V
Reece
Jeanette C
JC
Wang
Xiang Ju
XJ
Wilson
Kim M
KM
Suhrbier
Andreas
A
Khromykh
Alexander
A
D016915:AIDS Vaccines; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D015685:Fusion Proteins, gag-pol / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D005818:Genetic Engineering; D015497:HIV-1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation; D008254:Macaca nemestrina; D012093:Replicon; D018449:SAIDS Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000472:pathogenicity; D013601:T-Lymphocytes / Q000276:immunology; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D014902:West Nile virus / Q000235:genetics / Q000276:immunology / Q000378:metabolism
D016915:AIDS Vaccines; D000914:Antibodies, Viral; D015685:Fusion Proteins, gag-pol; D018449:SAIDS Vaccines; D014614:Vaccines, Synthetic