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Protective efficacy of recombinant influenza hemagglutinin ectodomain fusions

Mittal, N and Sengupta, N and Malladi, SK and Reddy, P and Bhat, M and Rajmani, RS and Sedeyn, K and Saelens, X and Dutta, S and Varadarajan, R (2021) Protective efficacy of recombinant influenza hemagglutinin ectodomain fusions. In: Viruses, 13 (9).

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Official URL: https://doi.org/10.3390/v13091710


In current seasonal influenza vaccines, neutralizing antibody titers directed against the hemagglutinin surface protein are the primary correlate of protection. These vaccines are, therefore, quantitated in terms of their hemagglutinin content. Adding other influenza surface proteins, such as neuraminidase and M2e, to current quadrivalent influenza vaccines would likely enhance vaccine efficacy. However, this would come with increased manufacturing complexity and cost. To address this issue, as a proof of principle, we have designed genetic fusions of hemagglutinin ectodomains from H3 and H1 influenza A subtypes. These recombinant H1-H3 hemagglutinin ectodomain fusions could be transiently expressed at high yield in mammalian cell culture using Expi293F suspension cells. Fusions were trimeric, and as stable in solution as their individual trimeric counterparts. Furthermore, the H1-H3 fusion constructs were antigenically intact based on their reactivity with a set of conformation-specific monoclonal antibodies. H1-H3 hemagglutinin ectodomain fusion immunogens, when formulated with the MF59 equivalent adjuvant squalene-in-water emulsion (SWE), induced H1 and H3-specific humoral immune responses equivalent to those induced with an equimolar mixture of individually expressed H1 and H3 ectodomains. Mice immunized with these ectodomain fusions were protected against challenge with heterologous H1N1 (Bel/09) and H3N2 (X-31) mouse-adapted viruses with higher neutralizing antibody titers against the H1N1 virus. Use of such ectodomain-fused immunogens would reduce the number of components in a vaccine formulation and allow for the inclusion of other protective antigens to increase influenza vaccine efficacy. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Item Type: Journal Article
Publication: Viruses
Publisher: MDPI
Additional Information: The copyright for this article belongs to Authors
Keywords: acetic acid; antigen; brilliant blue g; buffer; carbon; carbon dioxide; copper; ethanolamine; glycine; glycoprotein; hemagglutinin; histidine; imidazole; immunoglobulin G; influenza vaccine; membrane protein; neutralizing antibody; phosphate buffered saline; plasmid DNA; polysorbate 20; protein A; protein G; resin; sialidase; tissue plasminogen activator; trypsin; uranyl acetate, affinity chromatography; amino acid sequence; amino terminal sequence; anesthesia; animal cell; animal experiment; animal model; animal tissue; antigenicity; Article; binding affinity; body weight loss; carboxy terminal sequence; cell culture; Cytomegalovirus; drug efficacy; drug formulation; emulsion; enzyme linked immunosorbent assay; erythrocyte; flow rate; fluorescence; fluorometry; glycosylation; HEK293-F cell line; humoral immunity; immunization; incubation time; influenza; influenza A (H1N1); Influenza A virus (H3N2); light scattering; mammal cell; MDCK cell line; molecular weight; mouse; nonhuman; optical density; polyacrylamide gel electrophoresis; protein expression; protein secretion; refraction index; room temperature; size exclusion chromatography; staining; surface plasmon resonance; transmission electron microscopy
Department/Centre: Division of Biological Sciences > Molecular Biophysics Unit
Autonomous Societies / Centres > Society for Innovation and Development
Date Deposited: 02 Dec 2021 12:57
Last Modified: 02 Dec 2021 12:57
URI: http://eprints.iisc.ac.in/id/eprint/70076

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