Hemagglutinin sequence conservation guided stem immunogen design from influenza A H3 subtype

Mallajosyula, Vamsee Aditya V and Citron, Michael and Ferrara, Francesca and Temperton, Nigel J and Liang, Xiaoping and Flynn, Jessica A and Varadarajan, Raghavan (2015) Hemagglutinin sequence conservation guided stem immunogen design from influenza A H3 subtype. In: FRONTIERS IN IMMUNOLOGY, 6 .

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Abstract

Seasonal epidemics caused by influenza A (H1 and H3 subtypes) and B viruses are a major global health threat. The traditional, trivalent influenza vaccines have limited efficacy because of rapid antigenic evolution of the circulating viruses. This antigenic variability mediates viral escape from the host immune responses, necessitating annual vaccine updates. Influenza vaccines elicit a protective antibody response, primarily targeting the viral surface glycoprotein hemagglutinin (HA). However, the predominant humoral response is against the hypervariable head domain of HA, thereby restricting the breadth of protection. In contrast, the conserved, subdominant stem domain of HA is a potential ``universal'' vaccine candidate. We designed an HA stem-fragment immunogen from the 1968 pandemic H3N2 strain (A/Hong Kong/1/68) guided by a comprehensive H3 HA sequence conservation analysis. The biophysical properties of the designed immunogen were further improved by C-terminal fusion of a trimerization motif, ``isoleucine-zipper'', or ``foldon''. These immunogens elicited cross-reactive, antiviral antibodies and conferred partial protection against a lethal, homologous HK68 virus challenge in vivo. Furthermore, bacterial expression of these immunogens is economical and facilitates rapid scale-up.

Item Type:	Journal Article
Publication:	FRONTIERS IN IMMUNOLOGY
Publisher:	FRONTIERS RESEARCH FOUNDATION
Additional Information:	Copy right for this article belongs to the FRONTIERS RESEARCH FOUNDATION, PO BOX 110, LAUSANNE, 1015, SWITZERLAND
Keywords:	protein minimization; hemagglutinin stalk; subunit vaccine; pre-fusion conformation; antibody response; Escherichia coli
Department/Centre:	Division of Biological Sciences > Molecular Biophysics Unit
Date Deposited:	31 Jul 2015 14:55
Last Modified:	31 Jul 2015 14:55
URI:	http://eprints.iisc.ac.in/id/eprint/51992

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