Defining influenza a virus hemagglutinin antigenic drift by sequential monoclonal antibody selection

Suman R. Das, Scott E. Hensley, William L. Ince, Christopher B. Brooke, Anju Subba, Mark G. Delboy, Gustav Russ, James S. Gibbs, Jack R. Bennink, Jonathan W. Yewdell

Research output: Contribution to journalArticle

Abstract

Human influenza A virus (IAV) vaccination is limited by "antigenic drift," rapid antibody-driven escape reflecting amino acid substitutions in the globular domain of hemagglutinin (HA), the viral attachment protein. To better understand drift, we used anti-hemagglutinin monoclonal Abs (mAbs) to sequentially select IAV escape mutants. Twelve selection steps, each resulting in a single amino acid substitution in the hemagglutinin globular domain, were required to eliminate antigenicity defined by monoclonal or polyclonal Abs. Sequential mutants grow robustly, showing the structural plasticity of HA, although several hemagglutinin substitutions required an epistatic substitution in the neuraminidase glycoprotein to maximize growth. Selecting escape mutants from parental versus sequential variants with the same mAb revealed distinct escape repertoires, attributed to contextual changes in antigenicity and the mutation landscape. Since each hemagglutinin mutation potentially sculpts future mutation space, drift can follow many stochastic paths, undermining its unpredictability and underscoring the need for drift-insensitive vaccines.

Original languageEnglish (US)
Pages (from-to)314-323
Number of pages10
JournalCell Host and Microbe
Volume13
Issue number3
DOIs
StatePublished - Mar 13 2013
Externally publishedYes

Fingerprint

Hemagglutinins
Orthomyxoviridae
Monoclonal Antibodies
Influenza A virus
Amino Acid Substitution
Mutation
Neuraminidase
Viral Proteins
Human Influenza
Glycoproteins
Vaccination
Vaccines
Antibodies
Growth

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Virology

Cite this

Defining influenza a virus hemagglutinin antigenic drift by sequential monoclonal antibody selection. / Das, Suman R.; Hensley, Scott E.; Ince, William L.; Brooke, Christopher B.; Subba, Anju; Delboy, Mark G.; Russ, Gustav; Gibbs, James S.; Bennink, Jack R.; Yewdell, Jonathan W.

In: Cell Host and Microbe, Vol. 13, No. 3, 13.03.2013, p. 314-323.

Research output: Contribution to journalArticle

Das, SR, Hensley, SE, Ince, WL, Brooke, CB, Subba, A, Delboy, MG, Russ, G, Gibbs, JS, Bennink, JR & Yewdell, JW 2013, 'Defining influenza a virus hemagglutinin antigenic drift by sequential monoclonal antibody selection', Cell Host and Microbe, vol. 13, no. 3, pp. 314-323. https://doi.org/10.1016/j.chom.2013.02.008
Das, Suman R. ; Hensley, Scott E. ; Ince, William L. ; Brooke, Christopher B. ; Subba, Anju ; Delboy, Mark G. ; Russ, Gustav ; Gibbs, James S. ; Bennink, Jack R. ; Yewdell, Jonathan W. / Defining influenza a virus hemagglutinin antigenic drift by sequential monoclonal antibody selection. In: Cell Host and Microbe. 2013 ; Vol. 13, No. 3. pp. 314-323.
@article{b8f89043762a4f7cb925b6101ce5b88c,
title = "Defining influenza a virus hemagglutinin antigenic drift by sequential monoclonal antibody selection",
abstract = "Human influenza A virus (IAV) vaccination is limited by {"}antigenic drift,{"} rapid antibody-driven escape reflecting amino acid substitutions in the globular domain of hemagglutinin (HA), the viral attachment protein. To better understand drift, we used anti-hemagglutinin monoclonal Abs (mAbs) to sequentially select IAV escape mutants. Twelve selection steps, each resulting in a single amino acid substitution in the hemagglutinin globular domain, were required to eliminate antigenicity defined by monoclonal or polyclonal Abs. Sequential mutants grow robustly, showing the structural plasticity of HA, although several hemagglutinin substitutions required an epistatic substitution in the neuraminidase glycoprotein to maximize growth. Selecting escape mutants from parental versus sequential variants with the same mAb revealed distinct escape repertoires, attributed to contextual changes in antigenicity and the mutation landscape. Since each hemagglutinin mutation potentially sculpts future mutation space, drift can follow many stochastic paths, undermining its unpredictability and underscoring the need for drift-insensitive vaccines.",
author = "Das, {Suman R.} and Hensley, {Scott E.} and Ince, {William L.} and Brooke, {Christopher B.} and Anju Subba and Delboy, {Mark G.} and Gustav Russ and Gibbs, {James S.} and Bennink, {Jack R.} and Yewdell, {Jonathan W.}",
year = "2013",
month = "3",
day = "13",
doi = "10.1016/j.chom.2013.02.008",
language = "English (US)",
volume = "13",
pages = "314--323",
journal = "Cell Host and Microbe",
issn = "1931-3128",
publisher = "Cell Press",
number = "3",

}

TY - JOUR

T1 - Defining influenza a virus hemagglutinin antigenic drift by sequential monoclonal antibody selection

AU - Das, Suman R.

AU - Hensley, Scott E.

AU - Ince, William L.

AU - Brooke, Christopher B.

AU - Subba, Anju

AU - Delboy, Mark G.

AU - Russ, Gustav

AU - Gibbs, James S.

AU - Bennink, Jack R.

AU - Yewdell, Jonathan W.

PY - 2013/3/13

Y1 - 2013/3/13

N2 - Human influenza A virus (IAV) vaccination is limited by "antigenic drift," rapid antibody-driven escape reflecting amino acid substitutions in the globular domain of hemagglutinin (HA), the viral attachment protein. To better understand drift, we used anti-hemagglutinin monoclonal Abs (mAbs) to sequentially select IAV escape mutants. Twelve selection steps, each resulting in a single amino acid substitution in the hemagglutinin globular domain, were required to eliminate antigenicity defined by monoclonal or polyclonal Abs. Sequential mutants grow robustly, showing the structural plasticity of HA, although several hemagglutinin substitutions required an epistatic substitution in the neuraminidase glycoprotein to maximize growth. Selecting escape mutants from parental versus sequential variants with the same mAb revealed distinct escape repertoires, attributed to contextual changes in antigenicity and the mutation landscape. Since each hemagglutinin mutation potentially sculpts future mutation space, drift can follow many stochastic paths, undermining its unpredictability and underscoring the need for drift-insensitive vaccines.

AB - Human influenza A virus (IAV) vaccination is limited by "antigenic drift," rapid antibody-driven escape reflecting amino acid substitutions in the globular domain of hemagglutinin (HA), the viral attachment protein. To better understand drift, we used anti-hemagglutinin monoclonal Abs (mAbs) to sequentially select IAV escape mutants. Twelve selection steps, each resulting in a single amino acid substitution in the hemagglutinin globular domain, were required to eliminate antigenicity defined by monoclonal or polyclonal Abs. Sequential mutants grow robustly, showing the structural plasticity of HA, although several hemagglutinin substitutions required an epistatic substitution in the neuraminidase glycoprotein to maximize growth. Selecting escape mutants from parental versus sequential variants with the same mAb revealed distinct escape repertoires, attributed to contextual changes in antigenicity and the mutation landscape. Since each hemagglutinin mutation potentially sculpts future mutation space, drift can follow many stochastic paths, undermining its unpredictability and underscoring the need for drift-insensitive vaccines.

UR - http://www.scopus.com/inward/record.url?scp=84875145733&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84875145733&partnerID=8YFLogxK

U2 - 10.1016/j.chom.2013.02.008

DO - 10.1016/j.chom.2013.02.008

M3 - Article

C2 - 23498956

AN - SCOPUS:84875145733

VL - 13

SP - 314

EP - 323

JO - Cell Host and Microbe

JF - Cell Host and Microbe

SN - 1931-3128

IS - 3

ER -