title: Visualization of Alternative Functional Configurations of Influenza Virus Hemagglutinin Facilitates Rapid Selection of Complementing Vaccines in Emergency Situations.
abstract: Successful immunization against avian influenza virus (AIV) requires eliciting an adequate polyclonal response to AIV hemagglutinin (HA) subunit 1 (HA1) epitopes. Outbreaks of highly-pathogenic (HP) AIV subtype H5N1 can occur in vaccinated flocks in many endemic areas. Protection against emerging AIV is partly hindered by the limitations of vaccine production and transport, the use of leaky vaccines, and the use of multiple, and often antigenically-diverse, vaccines. It was hypothesized that the majority of alternative functional configurations (AFC) within the AIV HA1 can be represented by the pool of vaccine seed viruses currently in production because only a finite number of AFC are possible within each substructure of the molecule. Therefore, combinations of commercial vaccines containing complementing structural units (CSU) to each HA1 substructure can elicit responses to the totality of a given emerging AIV HA1 substructure isoforms. Analysis of homology-based 3D models of vaccine seed and emerging viruses facilitated the definition of HA1 AFC isoforms. CSU-based plots were used to predict which commercial vaccine combinations could have been used to cover nine selected AFC isoforms on recent Egyptian HP AIV H5N1 outbreak viruses. It is projected that expansion of the vaccine HA1 3D model database will improve international emergency responses to AIV.
authors.affiliation: Veterinary Virologist and Consultant, Cairo 11441, Egypt. drashrafmali@yahoo.com.
authors.forename: Ashraf
authors.initials: A
authors.lastname: Metwally
authors.affiliation: Virology Department, Faculty of Veterinary Medicine, Cairo University, Giza 12211, Egypt. ausama_yousif@cu.edu.eg.
authors.forename: Ausama
authors.initials: A
authors.lastname: Yousif
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D002645:Chickens; D004196:Disease Outbreaks / Q000517:prevention & control; D004534:Egypt / Q000453:epidemiology; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D007114:Immunization; D053124:Influenza A Virus, H5N1 Subtype / Q000145:classification / Q000235:genetics / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology*; D005585:Influenza in Birds / Q000188:drug therapy / Q000453:epidemiology / Q000276:immunology*; D008958:Models, Molecular; D009154:Mutation; D010802:Phylogeny; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid
chemical_list: D000914:Antibodies, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines
keywords: 3D modeling; alternative functional configurations; anchor sites; avian influenza virus; complementing structural units; escape mutants; fitness condition; hemagglutinin; vaccine combinations; vulnerable sites