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

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.

authors

Mallajosyula VV,Citron M,Ferrara F,Lu X,Callahan C,Heidecker GJ,Sarma SP,Flynn JA,Temperton NJ,Liang X,Varadarajan R

doi

10.1073/pnas.1402766111

subject

Has Abstract

pub_date

2014-06-24 00:00:00

pages

E2514-23

issue

25

eissn

0027-8424

issn

1091-6490

pii

1402766111

journal_volume

111

pub_type

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