Reports

Immunization by Avian H5 Influenza Hemagglutinin Mutants with Altered Receptor Binding Specificity

Zhi-Yong Yang,^1* Chih-Jen Wei,^1* Wing-Pui Kong,¹ Lan Wu,¹ Ling Xu,¹ David F. Smith,² Gary J. Nabel¹

Influenza virus entry is mediated by the receptor binding domain (RBD) of its spike, the hemagglutinin (HA). Adaptation of avian viruses to humans is associated with HA specificity for 2,6- rather than 2,3-linked sialic acid (SA) receptors. Here, we define mutations in influenza A subtype H5N1 (avian) HA that alter its specificity for SA either by decreasing 2,3- or increasing 2,6-SA recognition. RBD mutants were used to develop vaccines and monoclonal antibodies that neutralized new variants. Structure-based modification of HA specificity can guide the development of preemptive vaccines and therapeutic monoclonal antibodies that can be evaluated before the emergence of human-adapted H5N1 strains.

¹ Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health, Building 40, Room 4502, Mailstop Code MSC-3005, 40 Convent Drive, Bethesda, MD 20892, USA.
² Emory University School of Medicine, 1510 Clifton Road NE, Room 4035, Atlanta, GA 30322, USA.

^* These authors contributed equally to this work.

To whom correspondence should be addressed. E-mail: gnabel{at}nih.gov

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Comparative Efficacy of Neutralizing Antibodies Elicited by Recombinant Hemagglutinin Proteins from Avian H5N1 Influenza Virus.

C.-J. Wei, L. Xu, W.-P. Kong, W. Shi, K. Canis, J. Stevens, Z.-Y. Yang, A. Dell, S. M. Haslam, I. A. Wilson, et al. (2008)
J. Virol. 82, 6200-6208
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Infectivity Studies of Influenza Virus Hemagglutinin Receptor Binding Site Mutants in Mice.

J. Meisner, K. J. Szretter, K. C. Bradley, W. A. Langley, Z.-N. Li, B.-J. Lee, S. Thoennes, J. Martin, J. J. Skehel, R. J. Russell, et al. (2008)
J. Virol. 82, 5079-5083
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Novel Approach to the Development of Effective H5N1 Influenza A Virus Vaccines: Use of M2 Cytoplasmic Tail Mutants.

T. Watanabe, S. Watanabe, J. H. Kim, M. Hatta, and Y. Kawaoka (2008)
J. Virol. 82, 2486-2492
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Antigenic Profile of Avian H5N1 Viruses in Asia from 2002 to 2007.

W. L. Wu, Y. Chen, P. Wang, W. Song, S.-Y. Lau, J. M. Rayner, G. J. D. Smith, R. G. Webster, J. S. M. Peiris, T. Lin, et al. (2008)
J. Virol. 82, 1798-1807
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Structural basis for receptor specificity of influenza B virus hemagglutinin.

Q. Wang, X. Tian, X. Chen, and J. Ma (2007)
PNAS 104, 16874-16879
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