Epitopes described in "Broadly protective monoclonal antibodies against H3 influenza viruses following sequential immunization with different hemagglutinins."

Reference
Article Authors:Taia T Wang; Gene S Tan; Rong Hai; Natalie Pica; Erin Petersen; Thomas M Moran; Peter Palese
Article Title:Broadly protective monoclonal antibodies against H3 influenza viruses following sequential immunization with different hemagglutinins.
Reference Detail
Reference ID:1019178
Abstract:As targets of adaptive immunity, influenza viruses are characterized by the fluidity with which they respond to the selective pressure applied by neutralizing antibodies. This mutability of structural determinants of protective immunity is the obstacle in developing universal influenza vaccines. Towards the development of such vaccines and other immune therapies, our studies are designed to identify regions of influenza viruses that are conserved and that mediate virus neutralization. We have specifically focused on viruses of the H3N2 subtype, which have persisted as a principal source of influenza-related morbidity and mortality in humans since the pandemic of 1968. Three monoclonal antibodies have been identified that are broadly-neutralizing against H3 influenza viruses spanning 40 years. The antibodies react with the hemagglutinin glycoprotein and appear to bind in regions that are refractory to the structural variation required for viral escape from neutralization. The antibodies demonstrate therapeutic efficacy in mice against H3N2 virus infection and have potential for use in the treatment of human influenza disease. By mapping the binding region of one antibody, 12D1, we have identified a continuous region of the hemagglutinin that may act as an immunogen to elicit broadly protective immunity to H3 viruses. The anti-H3 monoclonal antibodies were identified after immunization of mice with the hemagglutinin of four different viruses (A/Hong Kong/1/1968, A/Alabama/1/1981, A/Beijing/47/1992, A/Wyoming/3/2003). This immunization schedule was designed to boost B cells specific for conserved regions of the hemagglutinin from distinct antigenic clusters. Importantly, our antibodies are of naturally occurring specificity rather than selected from cloned libraries, demonstrating that broad-spectrum humoral immunity to influenza viruses can be elicited in vivo.
Date:2010
Reference Type:Literature
PubMed ID:20195520
Journal:PLoS Pathog
Journal Volume:6
Article Pages:e1000796
Journal ISSN:1553-7374
Article Chemical List:Antibodies, Monoclonal;Antibodies, Neutralizing;Antibodies, Viral;Hemagglutinin Glycoproteins, Influenza Virus;Influenza Vaccines
Article MeSH List:Animals; Antibodies, Monoclonal(immunology); Antibodies, Neutralizing(immunology); Antibodies, Viral(immunology); Antibody Specificity; Blotting, Western; Enzyme-Linked Immunosorbent Assay; Female; Hemagglutinin Glycoproteins, Influenza Virus(immunology); Influenza A Virus, H3N2 Subtype(immunology); Influenza Vaccines(immunology); Mice; Mice, Inbred BALB C; Neutralization Tests; Orthomyxoviridae Infections(immunology; prevention & control)
Curation Last Updated:2014-07-16 22:28:03