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pubmed:abstractText |
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 alpha2,6- rather than alpha2,3-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 alpha2,3- or increasing alpha2,6-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.
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pubmed:affiliation |
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.
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