期刊
PLOS ONE
卷 9, 期 1, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0086254
关键词
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资金
- Intramural Research Program of the National Cancer Institute, National Institutes of Health (NCI/NIH)
- Bill and Melinda Gates Foundation [A39748]
- University of Washington Centers for AIDS Research Computational Biology Core [NIH P30 AI27757]
- Red de Investigacion de Sida (RIS) [RD06/04]
- Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Spanish FIPSE [36-0737-09]
- ICREA Funding Source: Custom
HIV sequence diversity and potential decoy epitopes are hurdles in the development of an effective AIDS vaccine. A DNA vaccine candidate comprising of highly conserved p24(gag) elements (CE) induced robust immunity in all 10 vaccinated macaques, whereas full-length gag DNA vaccination elicited responses to these conserved elements in only 5 of 11 animals, targeting fewer CE per animal. Importantly, boosting CE-primed macaques with DNA expressing full-length p55(gag) increased both magnitude of CE responses and breadth of Gag immunity, demonstrating alteration of the hierarchy of epitope recognition in the presence of pre-existing CE-specific responses. Inclusion of a conserved element immunogen provides a novel and effective strategy to broaden responses against highly diverse pathogens by avoiding decoy epitopes, while focusing responses to critical viral elements for which few escape pathways exist.
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