Mucosal prior to systemic application of recombinant adenovirus boosting is more immunogenic than systemic application twice but confers similar protection against SIV-challenge in DNA vaccine-primed macaques

• Published in: Virology (New York, N.Y.) Vol. 383; no. 2; pp. 300 - 309
• Main Authors: Schulte, Reiner, Suh, You-Suk, Sauermann, Ulrike, Ochieng, Washingtone, Sopper, Sieghart, Kim, Kwang S, Ahn, So-Shin, Park, Ki S, Stolte-Leeb, Nicole, Hunsmann, Gerhard, Sung, Young C, Stahl-Hennig, Christiane
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 20.01.2009
• Subjects: 60 APPLIED LIFE SCIENCES; Adenoviridae - genetics; ADENOVIRUS; AIDS; Animals; CELL PROLIFERATION; DNA; GENES; Immunization - methods; Immunization, Secondary - methods; Immunologic Memory; Infectious Disease; Injections, Intramuscular; Interferon-gamma - secretion; Macaca mulatta; MACACUS; Macaque; Mucosal immunization; Oropharynx - immunology; SAIDS Vaccines - administration & dosage; SAIDS Vaccines - immunology; Simian Acquired Immunodeficiency Syndrome - prevention & control; Simian immunodeficiency virus; Simian Immunodeficiency Virus - genetics; Simian Immunodeficiency Virus - immunology; SIV; T-Lymphocytes - immunology; Vaccine; VACCINES; Vaccines, DNA - administration & dosage; Vaccines, DNA - immunology; Viral Load; Viremia - prevention & control; SIV; Macaque; Vaccine; Adenovirus; Mucosal immunization
• ISSN: 0042-6822; 1096-0341
• DOI: 10.1016/j.virol.2008.10.012

Abstract We investigated the immunogenicity and efficacy of a bimodal prime/boost vaccine regimen given by various routes in the Simian immunodeficiency virus (SIV) rhesus monkey model for AIDS. Twelve animals were immunized with SIV DNA-vectors followed by the application of a recombinant adenovirus (rAd5) expressing the same genes either intramuscularly (i.m.) or by oropharyngeal spray. The second rAd5-application was given i.m. All vaccinees plus six controls were challenged orally with SIVmac239 12 weeks post-final immunization. Both immunization strategies induced strong SIV Gag-specific IFN-γ and T-cell proliferation responses and mediated a conservation of CD4+ memory T-cells and a reduction of viral load during peak viremia following infection. Interestingly, the mucosal group was superior to the systemic group regarding breadth and strength of SIV-specific T-cell responses and exhibited lower vector specific immune responses. Therefore, our data warrant the inclusion of mucosal vector application in a vaccination regimen which makes it less invasive and easier to apply.