Re: How 1918 flu antibodies fend off swine flu
<CITE><ABBR class=slug-jnl-abbrev title="Science Translational Medicine">Sci Transl Med</ABBR> 24 March 2010:
Vol. 2, Issue 24, p. 24ra21
DOI: 10.1126/scitranslmed.3000799 </CITE>
Cross-Neutralization of 1918 and 2009 Influenza Viruses: Role of Glycans in Viral Evolution and Vaccine Design
Chih-Jen Wei<SUP>1</SUP>,
Jeffrey C. Boyington<SUP>1</SUP>,
Kaifan Dai<SUP>1</SUP>,
Katherine V. Houser<SUP>2</SUP>,
Melissa B. Pearce<SUP>2</SUP>,
Wing-Pui Kong<SUP>1</SUP>,
Zhi-yong Yang<SUP>1</SUP>,
Terrence M. Tumpey<SUP>2</SUP> and
Gary J. Nabel<SUP>1</SUP>,
*
+ Author Affiliations<SUP></SUP>
<SUP>1</SUP>Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892?3005, USA. <SUP>2</SUP>Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.
*To whom correspondence should be addressed. E-mail:
gnabel@nih.gov
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.
Footnotes
Citation: C.-J. Wei, J. C. Boyington, K. Dai, K. V. Houser, M. B. Pearce, W.-P. Kong, Z-y.. Yang, T. M. Tumpey, G. J. Nabel, Cross-neutralization of 1918 and 2009 influenza viruses: Role of glycans in viral evolution and vaccine design.
Sci. Transl. Med. 2, 24ra21 (2010).
- Received December 31, 2009.
- Accepted March 4, 2010.
- Copyright ? 2010, American Association for the Advancement of Science
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