title: Better protective effects in rhesus macaques by combining systemic and mucosal application of a dual component vector vaccine after rectal SHIV89.6P challenge compared to systemic vaccination alone.
abstract: In this study we investigated the efficacy of a multigenic DNA prime/modified vaccinia Ankara (MVA)boost vaccine approach, followed by mucosal challenge with highly pathogenic simian-human immunodeficiency virus (SHIV) 89.6P, using different routes for vaccine delivery. After three times of DNA priming (SIVmac239, GagPol, and SHIV 89.6P Env) one vaccine group of monkeys was immunized with MVA systemically via intramuscular (IM) and intradermal (ID) application, and in another vaccine group the MVA booster immunization comprised the IM, ID, and atraumatic oral route. Although all vaccinees became infected after intra-rectal challenge with SHIV 89.6P, substantial protection as indicated by lower peak and set point viral loads and unambiguous preservation of CD4 T cells could be achieved. As we could only transiently detect low levels of neutralizing antibodies in some vaccinees, these antibodies did not seem to add to the protection in the vaccinees. Our results indicate that both preventive multigenic DNA prime/MVA booster immunization strategies promote the control of virus replication and protect from disease progression. We also demonstrated that combining mucosal and systemic vaccination mediated better protective effects compared to systemic vaccination alone.
authors.affiliation: German Primate Centre, Department of Virology and Immunology, Göttingen, Germany.
authors.forename: Nicole
authors.initials: N
authors.lastname: Stolte-Leeb
authors.forename: Kurt
authors.initials: K
authors.lastname: Bieler
authors.forename: Josef
authors.initials: J
authors.lastname: Kostler
authors.forename: Jonathan
authors.initials: J
authors.lastname: Heeney
authors.forename: Peter Ten
authors.initials: PT
authors.lastname: Haaft
authors.forename: You-Suk
authors.initials: YS
authors.lastname: Suh
authors.forename: Gerhard
authors.initials: G
authors.lastname: Hunsmann
authors.forename: Christiane
authors.initials: C
authors.lastname: Stahl-Hennig
authors.forename: Ralf
authors.initials: R
authors.lastname: Wagner
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D018791:CD4 Lymphocyte Count; D005260:Female; D005822:Genetic Vectors; D007117:Immunization, Secondary; D007271:Injections, Intradermal; D007273:Injections, Intramuscular; D008253:Macaca mulatta; D008297:Male; D009500:Neutralization Tests; D018449:SAIDS Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000517:prevention & control*; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology*; D014611:Vaccination / Q000379:methods*; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014616:Vaccinia virus / Q000235:genetics; D019562:Viral Load
chemical_list: D000914:Antibodies, Viral; D018449:SAIDS Vaccines; D019444:Vaccines, DNA