Design of immunogens to elicit broadly neutralizing antibodies against HIV targeting the CD4 binding site
Name
e2018338118.full.pdf
Description
Published version
Size
1.62 MB
Format
Adobe PDF
Checksum (MD5)
d9aaa1b4af065c6b41d2d30ba702e7d7
Author(s)
Conti, Simone
Kaczorowski, Kevin J
Song, Ge
Porter, Katelyn
Andrabi, Raiees
Burton, Dennis R
Chakraborty, Arup K
Karplus, Martin
Date Issued
2021
Journal
Proceedings of the National Academy of Sciences of the United States of America
Publisher
Proceedings of the National Academy of Sciences
Version
Final published version
Abstract
A vaccine which is effective against the HIV virus is considered to be the best solution to the ongoing global HIV/AIDS epidemic. In the past thirty years, numerous attempts to develop an effective vaccine have been made with little or no success, due, in large part, to the high mutability of the virus. More recent studies showed that a vaccine able to elicit broadly neutralizing antibodies (bnAbs), that is, antibodies that can neutralize a high fraction of global virus variants, has promise to protect against HIV. Such a vaccine has been proposed to involve at least three separate stages: First, activate the appropriate precursor B cells; second, shepherd affinity maturation along pathways toward bnAbs; and, third, polish the Ab response to bind with high affinity to diverse HIV envelopes (Env). This final stage may require immunization with a mixture of Envs. In this paper, we set up a framework based on theory and modeling to design optimal panels of antigens to use in such a mixture. The designed antigens are characterized experimentally and are shown to be stable and to be recognized by known HIV antibodies.
MIT Department
Massachusetts Institute of Technology. Institute for Medical Engineering & Science
Massachusetts Institute of Technology. Department of Chemical Engineering
Ragon Institute of MGH, MIT and Harvard
Massachusetts Institute of Technology. Department of Physics
Massachusetts Institute of Technology. Department of Chemistry
Terms of Use
Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
Persistent DSpace Link
DOI of Published Version
10.1073/pnas.2018338118
https://doi.org/10.1073/pnas.2018338118
