Translating HIV Sequences into Quantitative Fitness Landscapes Predicts Viral Vulnerabilities for Rational Immunogen Design

Andrew L. Ferguson, Jaclyn K. Mann, Saleha Omarjee, Thumbi Ndung'u, Bruce D. Walker, Arup K. Chakraborty

Research output: Contribution to journalArticle

Abstract

A prophylactic or therapeutic vaccine offers the best hope to curb the HIV-AIDS epidemic gripping sub-Saharan Africa, but it remains elusive. A major challenge is the extreme viral sequence variability among strains. Systematic means to guide immunogen design for highly variable pathogens like HIV are not available. Using computational models, we have developed an approach to translate available viral sequence data into quantitative landscapes of viral fitness as a function of the amino acid sequences of its constituent proteins. Predictions emerging from our computationally defined landscapes for the proteins of HIV-1 clade B Gag were positively tested against new in vitro fitness measurements and were consistent with previously defined in vitro measurements and clinical observations. These landscapes chart the peaks and valleys of viral fitness as protein sequences change and inform the design of immunogens and therapies that can target regions of the virus most vulnerable to selection pressure.

Original languageEnglish (US)
Pages (from-to)606-617
Number of pages12
JournalImmunity
Volume38
Issue number3
DOIs
StatePublished - Mar 21 2013

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Fingerprint Dive into the research topics of 'Translating HIV Sequences into Quantitative Fitness Landscapes Predicts Viral Vulnerabilities for Rational Immunogen Design'. Together they form a unique fingerprint.

  • Cite this

    Ferguson, A. L., Mann, J. K., Omarjee, S., Ndung'u, T., Walker, B. D., & Chakraborty, A. K. (2013). Translating HIV Sequences into Quantitative Fitness Landscapes Predicts Viral Vulnerabilities for Rational Immunogen Design. Immunity, 38(3), 606-617. https://doi.org/10.1016/j.immuni.2012.11.022