Mallajosyula, VVA and Swaroop, S and Varadarajan, R (2020) Influenza Hemagglutinin Head Domain Mimicry by Rational Design. In: Protein Journal, 39 (5). pp. 434-448.
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Abstract
Despite diligent vaccination efforts, influenza virus infection remains a major cause for respiratory-related illness across the globe. The less-than-optimal immunity conferred by the currently prescribed seasonal vaccines and protracted production times warrant the development of novel vaccines. Induction of an epitope-focused antibody response targeting known neutralization epitopes is a viable strategy to enhance the breadth of protection against rapidly evolving infectious viruses. We report the development of a design framework to mimic the hemagglutinin (HA) head fragment of H1-subtype viruses by delineating the interaction network of invariant residues lining the receptor binding site (RBS); a site targeted by cross-reactive neutralizing antibodies. The incorporation of multiple sequence alignment information in our algorithm to fix the construct termini and engineer rational mutations facilitates the facile extension of the design to heterologous (subtype-specific) influenza strains. We evaluated our design protocol by generating head fragments from divergent influenza A H1N1 A/Puerto Rico/8/34 and pH1N1 A/California/07/2009 strains that share a sequence identity of only 74.4 within the HA1 subunit. The designed immunogens exhibited characteristics of a well-ordered protein, and bound conformation-specific RBS targeting antibodies with high affinity, a desirable feature for putative vaccine candidates. Additionally, the bacterial expression of these immunogens provides a low-cost, rapidly scalable alternative. © 2020, Springer Science+Business Media, LLC, part of Springer Nature.
| Item Type: | Journal Article |
|---|---|
| Publication: | Protein Journal |
| Publisher: | Springer |
| Additional Information: | The copyright for this article belongs to the Authors. |
| Keywords: | influenza vaccine; Influenza virus hemagglutinin; neutralizing antibody; subunit vaccine; H1N1 virus hemagglutinin; influenza vaccine; Influenza virus hemagglutinin, algorithm; Article; binding site; computer model; controlled study; cross reaction; data analysis software; drug design; drug targeting; Escherichia coli; gel filtration chromatography; glycosylation; human; Influenza A virus (A/Puerto Rico/8/1934(H1N1)); molecular mimicry; mutation; nonhuman; protein engineering; protein stability; sequence alignment; virus strain; chemistry; genetics; Influenza A virus (H1N1); protein domain, Hemagglutinin Glycoproteins, Influenza Virus; Influenza A Virus, H1N1 Subtype; Influenza Vaccines; Molecular Mimicry; Protein Domains |
| Department/Centre: | Division of Biological Sciences > Molecular Biophysics Unit |
| Date Deposited: | 12 Jan 2023 08:59 |
| Last Modified: | 12 Jan 2023 08:59 |
| URI: | https://eprints.iisc.ac.in/id/eprint/79061 |
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