Highly effective control of an AIDS virus challenge in macaques by using vesicular stomatitis virus and modified vaccinia virus Ankara vaccine vectors in a single-boost protocol.
Previous studies have shown that vaccination and boosting of rhesus macaques with attenuated vesicular stomatitis virus (VSV) vectors encoding Env and Gag proteins of simian immunodeficiency virus-human immunodeficiency virus (SHIV) hybrid viruses protect rhesus macaques from AIDS after challenge with the highly pathogenic SHIV 89.6P (23). In the present study, we compared the effectiveness of a single prime-boost protocol consisting of VSV vectors expressing SHIV Env, Gag, and Pol proteins to that of a protocol consisting of a VSV vector prime followed with a single boost with modified vaccinia virus Ankara (MVA) expressing the same SHIV proteins. After challenge with SHIV 89.6P, MVA-boosted animals controlled peak challenge viral loads to less than 2 x 10(6) copies/ml (a level significantly lower than that seen with VSV-boosted animals and lower than those reported for other vaccine studies employing the same challenge). MVA-boosted animals have shown excellent preservation of CD4(+) T cells, while two of four VSV-boosted animals have shown significant loss of CD4(+) T cells. The improved protection in MVA-boosted animals correlates with trends toward stronger prechallenge CD8(+)-T-cell responses to SHIV antigens and stronger postchallenge SHIV-neutralizing antibody production.
Ramsburg
Elizabeth
E
Yale University School of Medicine, New Haven, Connecticut 06510, USA.
Rose
Nina F
NF
Marx
Preston A
PA
Mefford
Megan
M
Nixon
Douglas F
DF
Moretto
Walter J
WJ
Montefiori
David
D
Earl
Patricia
P
Moss
Bernard
B
Rose
John K
JK
D016915:AIDS Vaccines / Q000008:administration & dosage* / Q000235:genetics; D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000517:prevention & control; D000818:Animals; D001483:Base Sequence; D018791:CD4 Lymphocyte Count; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004274:DNA, Recombinant / Q000235:genetics; D005822:Genetic Vectors; D006678:HIV / Q000235:genetics / Q000302:isolation & purification; D015483:HIV Antibodies / Q000096:biosynthesis; D007117:Immunization, Secondary; D008253:Macaca mulatta; D018449:SAIDS Vaccines / Q000008:administration & dosage / Q000235:genetics; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000517:prevention & control; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000302:isolation & purification; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology; D014721:Vesicular stomatitis Indiana virus / Q000235:genetics / Q000276:immunology
D016915:AIDS Vaccines; D004274:DNA, Recombinant; D015483:HIV Antibodies; D018449:SAIDS Vaccines; D014614:Vaccines, Synthetic