Recombinant Adenovirus Vector Vaccine Studies

Nabel, Gary J.

Abstract

Adenovirus vectors have shown promise for vaccines, but one key hurdle is preexisting immunity to these viruses in humans. The VRC has been investigating the use of DNA priming and the use of alternate adenoviral serotypes or modified adenoviral vectors to overcome prior immunity. During the past year, the VRC has evaluated various modifications to Adenovirus serotype 5 and 35 as well as Ad 14, 26 and 28 vectors to determine if they remain immunogenic while reducing the impact of prior exposure to Ad5. The VRC conducted immunogenicity tests that was able to induce an effective immune response despite pre-exposure to Ad5. Several of these vectors are being further tested to evaluate their potential use in clinical trials.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Institute of Allergy and Infectious Diseases (NIAID)
• Type: Intramural Research (Z01)
• Project #: 1Z01AI005001-07
• Application #: 7732729
• Support Year: 7
• Fiscal Year: 2008
• Total Cost: $1,069,851

Institution

• Name: National Institute of Allergy and Infectious Diseases
• Country: United States

Publications

Wang, Lingshu; Cheng, Cheng; Ko, Sung-Youl et al. (2009) Delivery of human immunodeficiency virus vaccine vectors to the intestine induces enhanced mucosal cellular immunity. J Virol 83:7166-75

Ko, Sung-Youl; Cheng, Cheng; Kong, Wing-Pui et al. (2009) Enhanced induction of intestinal cellular immunity by oral priming with enteric adenovirus 41 vectors. J Virol 83:748-56

Cheng, Cheng; Gall, Jason G D; Kong, Wing-pui et al. (2007) Mechanism of ad5 vaccine immunity and toxicity: fiber shaft targeting of dendritic cells. PLoS Pathog 3:e25

Lemiale, Franck; Haddada, Hedi; Nabel, Gary J et al. (2007) Novel adenovirus vaccine vectors based on the enteric-tropic serotype 41. Vaccine 25:2074-84

Letvin, Norman L; Mascola, John R; Sun, Yue et al. (2006) Preserved CD4+ central memory T cells and survival in vaccinated SIV-challenged monkeys. Science 312:1530-3

Mattapallil, Joseph J; Douek, Daniel C; Buckler-White, Alicia et al. (2006) Vaccination preserves CD4 memory T cells during acute simian immunodeficiency virus challenge. J Exp Med 203:1533-41

Acierno, Paula M; Schmitz, Jorn E; Gorgone, Darci A et al. (2006) Preservation of functional virus-specific memory CD8+ T lymphocytes in vaccinated, simian human immunodeficiency virus-infected rhesus monkeys. J Immunol 176:5338-45

Wu, Lan; Kong, Wing-Pui; Nabel, Gary J (2005) Enhanced breadth of CD4 T-cell immunity by DNA prime and adenovirus boost immunization to human immunodeficiency virus Env and Gag immunogens. J Virol 79:8024-31

Mascola, John R; Sambor, Anna; Beaudry, Kristin et al. (2005) Neutralizing antibodies elicited by immunization of monkeys with DNA plasmids and recombinant adenoviral vectors expressing human immunodeficiency virus type 1 proteins. J Virol 79:771-9

Santra, Sampa; Seaman, Michael S; Xu, Ling et al. (2005) Replication-defective adenovirus serotype 5 vectors elicit durable cellular and humoral immune responses in nonhuman primates. J Virol 79:6516-22