Journal
PLOS PATHOGENS
Volume 12, Issue 8, Pages -Publisher
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.ppat.1005815
Keywords
-
Categories
Funding
- International AIDS Vaccine Initiative Neutralizing Antibody Consortium
- International AIDS Vaccine Initiative Neutralizing Antibody Center
- Bill and Melinda Gates Foundation CAVD award
- CAVD
- Ragon Institute of MGH, MIT
- Ragon Institute of MGH, Harvard
- Bayer Science and Education Foundation
- National Institute of Allergy and Infectious Diseases [P01AI081625, CHAVI-ID 1UM1 AI100663, P01 AI110657, R01 AI084817]
- DOE, Basic Energy Sciences, Office of Science [DE-AC02-06CH11357]
- NCI [Y1-CO-1020]
- NIGMS [Y1-GM-1104]
Ask authors/readers for more resources
An optimal HIV vaccine should induce broadly neutralizing antibodies (bnAbs) that neutralize diverse viral strains and subtypes. However, potent bnAbs develop in only a small fraction of HIV-infected individuals, all contain rare features such as extensive mutation, insertions, deletions, and/or long complementarity-determining regions, and some are polyreactive, casting doubt on whether bnAbs to HIV can be reliably induced by vaccination. We engineered two potent VRC01-class bnAbs that minimized rare features. According to a quantitative features frequency analysis, the set of features for one of these minimally mutated bnAbs compared favorably with all 68 HIV bnAbs analyzed and was similar to antibodies elicited by common vaccines. This same minimally mutated bnAb lacked polyreactivity in four different assays. We then divided the minimal mutations into spatial clusters and dissected the epitope components interacting with those clusters, by mutational and crystallographic analyses coupled with neutralization assays. Finally, by synthesizing available data, we developed a working-concept boosting strategy to select the mutation clusters in a logical order following a germline-targeting prime. We have thus developed potent HIV bnAbs that may be more tractable vaccine goals compared to existing bnAbs, and we have proposed a strategy to elicit them. This reductionist approach to vaccine design, guided by antibody and antigen structure, could be applied to design candidate vaccines for other HIV bnAbs or protective Abs against other pathogens.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available