Immunization of rhesus macaques with a DNA prime/modified vaccinia virus Ankara boost regimen induces broad simian immunodeficiency virus (SIV)-specific T-cell responses and reduces initial viral replication but does not prevent disease progression following challenge with pathogenic SIVmac239.
Producing a prophylactic vaccine for human immunodeficiency virus (HIV) has proven to be a challenge. Most biological isolates of HIV are difficult to neutralize, so that conventional subunit-based antibody-inducing vaccines are unlikely to be very effective. In the rhesus macaque model, some protection was afforded by DNA/recombinant viral vector vaccines. However, these studies used as the challenge virus SHIV-89.6P, which is neutralizable, making it difficult to determine whether the observed protection was due to cellular immunity, humoral immunity, or a combination of both. In this study, we used a DNA prime/modified vaccinia virus Ankara boost regimen to immunize rhesus macaques against nearly all simian immunodeficiency virus (SIV) proteins. These animals were challenged intrarectally with pathogenic molecularly cloned SIVmac239, which is resistant to neutralization. The immunization regimen resulted in the induction of virus-specific CD8(+) and CD4(+) responses in all vaccinees. Although anamnestic neutralizing antibody responses against laboratory-adapted SIVmac251 developed after the challenge, no neutralizing antibodies against SIVmac239 were detectable. Vaccinated animals had significantly reduced peak viremia compared with controls (P < 0.01). However, despite the induction of virus-specific cellular immune responses and reduced peak viral loads, most animals still suffered from gradual CD4 depletion and progressed to disease.
Horton
Helen
H
Wisconsin Regional Primate Research Center, University of Wisconsin, Madison, Wisconsin 53715, USA.
Vogel
Thorsten U
TU
Carter
Donald K
DK
Vielhuber
Kathy
K
Fuller
Deborah H
DH
Shipley
Tim
T
Fuller
James T
JT
Kunstman
Kevin J
KJ
Sutter
Gerd
G
Montefiori
David C
DC
Erfle
Volker
V
Desrosiers
Ronald C
RC
Wilson
Nancy
N
Picker
Louis J
LJ
Wolinsky
Steven M
SM
Wang
Chenxi
C
Allison
David B
DB
Watkins
David I
DI
D016915:AIDS Vaccines / Q000276:immunology*; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D006801:Humans; D007117:Immunization, Secondary; D007371:Interferon-gamma / Q000378:metabolism; D008253:Macaca mulatta; D009500:Neutralization Tests; D018449:SAIDS Vaccines / Q000276:immunology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000517:prevention & control*; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D014611:Vaccination; D019444:Vaccines, DNA / Q000276:immunology*; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology*; D019562:Viral Load; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology
D016915:AIDS Vaccines; D000914:Antibodies, Viral; D018449:SAIDS Vaccines; D019444:Vaccines, DNA; D014764:Viral Proteins; D007371:Interferon-gamma