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 vectors to determine if they remain immunogenic while reducing the impact of prior exposure to Ad5. The VRC identified a chimeric adenovector incorporating Ad5 and Ad35 elements that was able to induce an effective immune response despite pre-exposure to Ad5. This vector is advancing into clinical trials.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Intramural Research (Z01)
Project #
1Z01AI005001-06
Application #
7592377
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
6
Fiscal Year
2007
Total Cost
$887,840
Indirect Cost

  Institution

Name
National Institute of Allergy and Infectious Diseases
Department
Type
DUNS #
City
State
Country
United States
Zip Code

  Publications

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
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
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

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