Vaccination of macaques with SIV immunogens delivered by Venezuelan equine encephalitis virus replicon particle vectors followed by a mucosal challenge with SIVsmE660.
VEE replicon particles (VRP), non-propagating vaccine vectors derived from Venezuelan equine encephalitis virus (VEE), were engineered to express immunogens from the cloned isolate SIVsmH-4, combined in a vaccine cocktail and inoculated subcutaneously to immunize rhesus macaques. The virulent, uncloned challenge stock, SIVsmE660, represented a type of heterologous challenge and the intrarectal challenge modeled infection across a mucosal surface. Prechallenge neutralizing antibodies against SIVsmH-4 were induced in all vaccinates, and a prechallenge cellular immune response could be detected in one of six. Post-challenge, virus loads were reduced at the peak, at set point and at termination (41 weeks post-challenge), although these differences did not reach statistical significance. Significantly elevated levels of CD4+ T cells were observed post-challenge. A strong correlation was noted between a net increase in CD4+ T cell count and lowered virus load at set point.
Johnston
Robert E
RE
Carolina Vaccine Institute, School of Medicine, University of North Carolina, CB#7292, Chapel Hill, NC 27599, USA.
Johnson
Philip R
PR
Connell
Mary J
MJ
Montefiori
David C
DC
West
Ande
A
Collier
Martha L
ML
Cecil
Chad
C
Swanstrom
Ronald
R
Frelinger
Jeffrey A
JA
Davis
Nancy L
NL
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D018791:CD4 Lymphocyte Count; D004195:Disease Models, Animal; D004666:Encephalitis Virus, Venezuelan Equine / Q000235:genetics*; D005822:Genetic Vectors; D007111:Immunity, Cellular; D007279:Injections, Subcutaneous; D008253:Macaca mulatta; D009500:Neutralization Tests; D012093:Replicon / Q000235:genetics; D018449:SAIDS Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000517:prevention & control*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D019562:Viral Load; D014765:Viral Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*
D000914:Antibodies, Viral; D018449:SAIDS Vaccines; D014614:Vaccines, Synthetic; D014765:Viral Vaccines