title: 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.
abstract: 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.
authors.affiliation: Wisconsin Regional Primate Research Center, University of Wisconsin, Madison, Wisconsin 53715, USA.
authors.forename: Helen
authors.initials: H
authors.lastname: Horton
authors.forename: Thorsten U
authors.initials: TU
authors.lastname: Vogel
authors.forename: Donald K
authors.initials: DK
authors.lastname: Carter
authors.forename: Kathy
authors.initials: K
authors.lastname: Vielhuber
authors.forename: Deborah H
authors.initials: DH
authors.lastname: Fuller
authors.forename: Tim
authors.initials: T
authors.lastname: Shipley
authors.forename: James T
authors.initials: JT
authors.lastname: Fuller
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Kunstman
authors.forename: Gerd
authors.initials: G
authors.lastname: Sutter
authors.forename: David C
authors.initials: DC
authors.lastname: Montefiori
authors.forename: Volker
authors.initials: V
authors.lastname: Erfle
authors.forename: Ronald C
authors.initials: RC
authors.lastname: Desrosiers
authors.forename: Nancy
authors.initials: N
authors.lastname: Wilson
authors.forename: Louis J
authors.initials: LJ
authors.lastname: Picker
authors.forename: Steven M
authors.initials: SM
authors.lastname: Wolinsky
authors.forename: Chenxi
authors.initials: C
authors.lastname: Wang
authors.forename: David B
authors.initials: DB
authors.lastname: Allison
authors.forename: David I
authors.initials: DI
authors.lastname: Watkins
mesh_terms: 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
chemical_list: D016915:AIDS Vaccines; D000914:Antibodies, Viral; D018449:SAIDS Vaccines; D019444:Vaccines, DNA; D014764:Viral Proteins; D007371:Interferon-gamma