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

Mallajosyula, Vamsee V A, Citron, Michael, Ferrara, Francesca, Temperton, Nigel J., Liang, Xiaoping, Flynn, Jessica A, Varadarajan, Raghavan (2015) Hemagglutinin sequence conservation guided stem immunogen design from influenza A H3 subtype. Frontiers in Immunology, 6 (329). pp. 1-22. ISSN 1664-3224. (doi:10.3389/fimmu.2015.00329)

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http://dx.doi.org/10.3389/fimmu.2015.00329

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: Article
DOI/Identification number: 10.3389/fimmu.2015.00329
Uncontrolled keywords: Protein minimization, hemagglutinin stalk, subunit vaccine, pre-fusion conformation, antibody response, Escherichia coli
Subjects: Q Science > QR Microbiology > QR355 Virology
Divisions: Faculties > Sciences > Medway School of Pharmacy
Depositing User: Nigel Temperton
Date Deposited: 15 Jun 2015 14:46 UTC
Last Modified: 29 May 2019 14:42 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/49023 (The current URI for this page, for reference purposes)
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