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Influenza hemagglutinin stem-fragment immunogen elicits broadly neutralizing antibodies and confers heterologous protection

Mallajosyula, Vamsee V.A., Citron, Michael, Ferrara, Francesca, Lu, Xianghan, Callahan, Cheryl, Heidecker, Gwendolyn J., Sarma, Siddhartha P., Flynn, Jessica A., Temperton, Nigel J., Liang, Xiaoping, and others. (2014) Influenza hemagglutinin stem-fragment immunogen elicits broadly neutralizing antibodies and confers heterologous protection. Proceedings of the National Academy of Sciences of the United States of America, 111 (25). ISSN 0027-8424. E-ISSN 1091-6490. (doi:10.1073/pnas.1402766111) (KAR id:41433)

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http://dx.doi.org/10.1073/pnas.1402766111

Abstract

Influenza hemagglutinin (HA) is the primary target of the humoral response during infection/vaccination. Current influenza vaccines typically fail to elicit/boost broadly neutralizing antibodies (bnAbs), thereby limiting their efficacy. Although several bnAbs bind to the conserved stem domain of HA, focusing the immune response to this conserved stem in the presence of the immunodominant, variable head domain of HA is challenging. We report the design of a thermotolerant, disulfide-free, and trimeric HA stem-fragment immunogen which mimics the native, prefusion conformation of HA and binds conformation specific bnAbs with high affinity. The immunogen elicited bnAbs that neutralized highly divergent group 1 (H1 and H5 subtypes) and 2 (H3 subtype) influenza virus strains in vitro. Stem immunogens designed from unmatched, highly drifted influenza strains conferred robust protection against a lethal heterologous A/Puerto Rico/8/34 virus challenge in vivo. Soluble, bacterial expression of such designed immunogens allows for rapid scale-up during pandemic outbreaks.

Item Type: Article
DOI/Identification number: 10.1073/pnas.1402766111
Uncontrolled keywords: Medway School of Pharmacy
Subjects: Q Science > QR Microbiology > QR355 Virology
Divisions: Divisions > Division of Natural Sciences > Medway School of Pharmacy
Depositing User: Nigel Temperton
Date Deposited: 16 Jun 2014 09:45 UTC
Last Modified: 16 Feb 2021 12:53 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/41433 (The current URI for this page, for reference purposes)
Temperton, Nigel J.: https://orcid.org/0000-0002-7978-3815
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