Optimal immunization cocktails can promote induction of broadly neutralizing Abs against highly mutable pathogens
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Shaffer-2016-Optimal immunization cocktails ca.pdf
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Author(s)
Moore, Penny L.
Shaffer, James S
Kardar, Mehran
Chakraborty, Arup K
Date Issued
October 2016
Journal
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences (U.S.)
Citation
Shaffer, J. Scott; Moore, Penny L.; Kardar, Mehran and Chakraborty, Arup K. “Optimal Immunization Cocktails Can Promote Induction of Broadly Neutralizing Abs Against Highly Mutable Pathogens.” Proceedings of the National Academy of Sciences 113, no. 45 (October 2016): E7039–E7048. © National Academy of Sciences
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Final published version
Abstract
Strategies to elicit Abs that can neutralize diverse strains of a highly mutable pathogen are likely to result in a potent vaccine. Broadly neutralizing Abs (bnAbs) against HIV have been isolated from patients, proving that the human immune system can evolve them. Using computer simulations and theory, we study immunization with diverse mixtures of variant antigens (Ags). Our results show that particular choices for the number of variant Ags and the mutational distances separating them maximize the probability of inducing bnAbs. The variant Ags represent potentially conflicting selection forces that can frustrate the Darwinian evolutionary process of affinity maturation. An intermediate level of frustration maximizes the chance of evolving bnAbs. A simple model makes vivid the origin of this principle of optimal frustration. Our results, combined with past studies, suggest that an appropriately chosen permutation of immunization with an optimally designed mixture (using the principles that we describe) and sequential immunization with variant Ags that are separated by relatively large mutational distances may best promote the evolution of bnAbs.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Mechanical Engineering
Massachusetts Institute of Technology. Department of Physics
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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.
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DOI of Published Version
https://doi.org/10.1073/pnas.1614940113
