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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.
AuthorsNicole Stolte-Leeb, Kurt Bieler, Josef Kostler, Jonathan Heeney, Peter Ten Haaft, You-Suk Suh, Gerhard Hunsmann, Christiane Stahl-Hennig, Ralf Wagner
JournalViral immunology (Viral Immunol) Vol. 21 Issue 2 Pg. 235-46 (Jun 2008) ISSN: 0882-8245 [Print] United States
PMID18476770 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antibodies, Viral
  • SAIDS Vaccines
  • Vaccines, DNA
Topics
  • Administration, Oral
  • Animals
  • Antibodies, Viral (blood)
  • CD4 Lymphocyte Count
  • Female
  • Genetic Vectors
  • Immunization, Secondary
  • Injections, Intradermal
  • Injections, Intramuscular
  • Macaca mulatta
  • Male
  • Neutralization Tests
  • SAIDS Vaccines (administration & dosage, immunology)
  • Simian Acquired Immunodeficiency Syndrome (prevention & control)
  • Simian Immunodeficiency Virus (genetics, immunology)
  • Vaccination (methods)
  • Vaccines, DNA (administration & dosage, genetics, immunology)
  • Vaccinia virus (genetics)
  • Viral Load

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