Cross-neutralization of 1918 and 2009 influenza viruses

Role of glycans in viral evolution and vaccine design

Chih Jen Wei, Jeffrey C. Boyington, Kaifan Dai, Katherine V. Houser, Melissa B. Pearce, Wing Pui Kong, Zhi Yong Yang, Terrence M. Tumpey, Gary J. Nabel

Research output: Contribution to journalArticle

Abstract

New strains of H1N1 influenza virus have emerged episodically over the last century to cause human pandemics, notably in 1918 and recently in 2009. Pandemic viruses typically evolve into seasonal forms that develop resistance to antibody neutralization, and cross-protection between strains separated by more than 3 years is uncommon. Here, we define the structural basis for cross-neutralization between two temporally distant pandemic influenza viruses-from 1918 and 2009. Vaccination of mice with the 1918 strain protected against subsequent lethal infection by 2009 virus. Both were resistant to antibodies directed against a seasonal influenza, A/New Caledonia/20/1999 (1999 NC), which was insensitive to antisera to the pandemic strains. Pandemic strain-neutralizing antibodies were directed against a subregion of the hemagglutinin (HA) receptor binding domain that is highly conserved between the 1918 and the 2009 viruses. In seasonal strains, this region undergoes amino acid diversification but is shielded from antibody neutralization by two highly conserved glycosylation sites absent in the pandemic strains. Pandemic HA trimers modified by glycosylation at these positions were resistant to neutralizing antibodies to wild-type HA. Yet, antisera generated against the glycosylated HA mutant neutralized it, suggesting that the focus of the immune response can be selectively changed with this modification. Collectively, these findings define critical determinants of H1N1 viral evolution and have implications for vaccine design. Immunization directed to conserved receptor binding domain subregions of pandemic viruses could potentially protect against similar future pandemic viruses, and vaccination with glycosylated 2009 pandemic virus may limit its further spread and transformation into a seasonal influenza.

Original languageEnglish (US)
JournalScience Translational Medicine
Volume2
Issue number24
DOIs
StatePublished - 2010
Externally publishedYes

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Viral Vaccines
Pandemics
Orthomyxoviridae
Polysaccharides
Hemagglutinins
Viruses
Neutralizing Antibodies
Glycosylation
Human Influenza
Antibodies
Immune Sera
Vaccination
New Caledonia
Cross Protection
H1N1 Subtype Influenza A Virus
Virus Diseases
Immunization
Vaccines

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Cross-neutralization of 1918 and 2009 influenza viruses : Role of glycans in viral evolution and vaccine design. / Wei, Chih Jen; Boyington, Jeffrey C.; Dai, Kaifan; Houser, Katherine V.; Pearce, Melissa B.; Kong, Wing Pui; Yang, Zhi Yong; Tumpey, Terrence M.; Nabel, Gary J.

In: Science Translational Medicine, Vol. 2, No. 24, 2010.

Research output: Contribution to journalArticle

Wei, CJ, Boyington, JC, Dai, K, Houser, KV, Pearce, MB, Kong, WP, Yang, ZY, Tumpey, TM & Nabel, GJ 2010, 'Cross-neutralization of 1918 and 2009 influenza viruses: Role of glycans in viral evolution and vaccine design', Science Translational Medicine, vol. 2, no. 24. https://doi.org/10.1126/scitranslmed.3000799
Wei, Chih Jen ; Boyington, Jeffrey C. ; Dai, Kaifan ; Houser, Katherine V. ; Pearce, Melissa B. ; Kong, Wing Pui ; Yang, Zhi Yong ; Tumpey, Terrence M. ; Nabel, Gary J. / Cross-neutralization of 1918 and 2009 influenza viruses : Role of glycans in viral evolution and vaccine design. In: Science Translational Medicine. 2010 ; Vol. 2, No. 24.
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