Immunization by avian H5 influenza hemagglutinin mutants with altered receptor binding specificity.
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.
Yang
Zhi-Yong
ZY
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.
Wei
Chih-Jen
CJ
Kong
Wing-Pui
WP
Wu
Lan
L
Xu
Ling
L
Smith
David F
DF
Nabel
Gary J
GJ
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology; D002236:Carbohydrate Conformation; D002460:Cell Line; D005260:Female; D005814:Genes, Viral; D006385:Hemagglutination Inhibition Tests; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D053124:Influenza A Virus, H5N1 Subtype / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D007252:Influenza Vaccines / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009154:Mutation; D009500:Neutralization Tests; D011991:Receptors, Virus / Q000378:metabolism*; D012794:Sialic Acids / Q000378:metabolism*; D014611:Vaccination
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D011991:Receptors, Virus; D012794:Sialic Acids; C109963:hemagglutinin, avian influenza A virus
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