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Open AccessArticle

Strain-Dependent Impact of G and SH Deletions Provide New Insights for Live-Attenuated HMPV Vaccine Development

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Laboratoire de Virologie et Pathologie Humaine—VirPath team, Centre International de Recherche en Infectiologie (CIRI), INSERM U1111, CNRS UMR5308, ENS Lyon, Université Claude Bernard Lyon 1, Université de Lyon, 69008 Lyon, France
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Centre de Recherche en Infectiologie of the Centre Hospitalier Universitaire de Québec and Université Laval, QC G1V 4G2, Canada
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VirNext, Faculté de Médecine RTH Laennec, Université Claude Bernard Lyon 1, Université de Lyon, 69008 Lyon, France
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Quebec Heart and Lung Institute, Laval University, Quebec City, QC G1V 4G5, Canada
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Laboratoire de Virologie, Centre National de Référence des virus Influenza, Institut des Agents Infectieux, Groupement Hospitalier Nord, Hospices Civils de Lyon, 69004 Lyon, France
*
Authors to whom correspondence should be addressed.
M.-R.C. and G.B. are co-last authors.
Vaccines 2019, 7(4), 164; https://doi.org/10.3390/vaccines7040164
Received: 2 October 2019 / Revised: 23 October 2019 / Accepted: 23 October 2019 / Published: 30 October 2019
(This article belongs to the Section Vaccines against Infectious Diseases)
Human metapneumovirus (HMPV) is a major pediatric respiratory pathogen with currently no specific treatment or licensed vaccine. Different strategies to prevent this infection have been evaluated, including live-attenuated vaccines (LAV) based on SH and/or G protein deletions. This approach showed promising outcomes but has not been evaluated further using different viral strains. In that regard, we previously showed that different HMPV strains harbor distinct in vitro fusogenic and in vivo pathogenic phenotypes, possibly influencing the selection of vaccine strains. In this study, we investigated the putative contribution of the low conserved SH or G accessory proteins in such strain-dependent phenotypes and generated recombinant wild type (WT) and SH- or G-deleted viruses derived from two different patient-derived HMPV strains, A1/C-85473 and B2/CAN98-75. The ΔSH and ΔG deletions led to different strain-specific phenotypes in both LLC-MK2 cell and reconstituted human airway epithelium models. More interestingly, the ΔG-85473 and especially ΔSH-C-85473 recombinant viruses conferred significant protection against HMPV challenge and induced immunogenicity against a heterologous strain. In conclusion, our results show that the viral genetic backbone should be considered in the design of live-attenuated HMPV vaccines, and that a SH-deleted virus based on the A1/C-85473 HMPV strain could be a promising LAV candidate as it is both attenuated and protective in mice while being efficiently produced in a cell-based system. View Full-Text
Keywords: human metapneumovirus (HMPV); live-attenuated vaccine (LAV); G protein; SH protein; gene deletion; reverse genetics human metapneumovirus (HMPV); live-attenuated vaccine (LAV); G protein; SH protein; gene deletion; reverse genetics
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Dubois, J.; Pizzorno, A.; Cavanagh, M.-H.; Padey, B.; Nicolas de Lamballerie, C.; Uyar, O.; Venable, M.-C.; Carbonneau, J.; Traversier, A.; Julien, T.; Lavigne, S.; Couture, C.; Lina, B.; Hamelin, M.-È.; Terrier, O.; Rosa-Calatrava, M.; Boivin, G. Strain-Dependent Impact of G and SH Deletions Provide New Insights for Live-Attenuated HMPV Vaccine Development. Vaccines 2019, 7, 164.

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