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

Mallajosyula, Vamsee VA and Citron, Michael and Ferrara, Francesca and Lu, Xianghan and Callahan, Cheryl and Heidecker, Gwendolyn J and Sarma, Siddhartha P and Flynn, Jessica A and Temperton, Nigel J and Liang, Xiaoping and Varadarajan, Raghavan (2014) Influenza hemagglutinin stem-fragment immunogen elicits broadly neutralizing antibodies and confers heterologous protection. In: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 111 (25). E2514-E2523.

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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:	Journal Article
Publication:	PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Publisher:	NATL ACAD SCIENCES
Additional Information:	Copy right for this article belongs to the NATL ACAD SCIENCES, 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
Keywords:	hemagglutinin stalk; stabilization; cross-protection; pandemic preparedness; Escherichia coli
Department/Centre:	Division of Biological Sciences > Molecular Biophysics Unit
Date Deposited:	11 Aug 2014 04:55
Last Modified:	11 Aug 2014 07:26
URI:	http://eprints.iisc.ac.in/id/eprint/49542

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