Large-scale analysis of B-cell epitopes on influenza virus hemagglutinin - Implications for cross-reactivity of neutralizing antibodies

Jing Sun, Ulrich J. Kudahl, Christian Simon, Zhiwei Cao, Ellis L. Reinherz, Vladimir Brusic

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Influenza viruses continue to cause substantial morbidity and mortality worldwide. Fast gene mutation on surface proteins of influenza virus result in increasing resistance to current vaccines and available antiviral drugs. Broadly neutralizing antibodies (bnAbs) represent targets for prophylactic and therapeutic treatments of influenza. We performed a systematic bioinformatics study of cross-reactivity of neutralizing antibodies (nAbs) against influenza virus surface glycoprotein hemagglutinin (HA). This study utilized the available crystal structures of HA complexed with the antibodies for the analysis of tens of thousands of HA sequences. The detailed description of B-cell epitopes, measurement of epitope area similarity among different strains, and estimation of antibody neutralizing coverage provide insights into cross-reactivity status of existing nAbs against influenza virus. We have developed a method to assess the likely cross-reactivity potential of bnAbs for influenza strains, either newly emerged or existing. Our method catalogs influenza strains by a new concept named discontinuous peptide, and then provide assessment of cross-reactivity. Potentially cross-reactive strains are those that share 100% identity with experimentally verified neutralized strains. By cataloging influenza strains and their B-cell epitopes for known bnAbs, our method provides guidance for selection of representative strains for further experimental design. The knowledge of sequences, their B-cell epitopes, and differences between historical influenza strains, we enhance our preparedness and the ability to respond to the emerging pandemic threats.

Original languageEnglish
Article numberArticle 38
JournalFrontiers in Immunology
Volume5
Issue numberFEB
DOIs
Publication statusPublished - 2014
Externally publishedYes

Fingerprint

B-Lymphocyte Epitopes
Hemagglutinins
Neutralizing Antibodies
Orthomyxoviridae
Human Influenza
Cataloging
Membrane Glycoproteins
Pandemics
Computational Biology
Antiviral Agents
Epitopes
Membrane Proteins
Research Design
Vaccines
Morbidity
Peptides
Mutation
Mortality
Antibodies
Genes

Keywords

  • B-cell epitope
  • Cross-reactivity
  • Discontinuous peptide
  • Influenza virus
  • Neutralizing antibodies

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Large-scale analysis of B-cell epitopes on influenza virus hemagglutinin - Implications for cross-reactivity of neutralizing antibodies. / Sun, Jing; Kudahl, Ulrich J.; Simon, Christian; Cao, Zhiwei; Reinherz, Ellis L.; Brusic, Vladimir.

In: Frontiers in Immunology, Vol. 5, No. FEB, Article 38, 2014.

Research output: Contribution to journalArticle

Sun, Jing ; Kudahl, Ulrich J. ; Simon, Christian ; Cao, Zhiwei ; Reinherz, Ellis L. ; Brusic, Vladimir. / Large-scale analysis of B-cell epitopes on influenza virus hemagglutinin - Implications for cross-reactivity of neutralizing antibodies. In: Frontiers in Immunology. 2014 ; Vol. 5, No. FEB.
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