Strain-dependent impact of G and SH deletions provide new insights for live-attenuated HMPV vaccine development

摘要: Abstract 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 evaluated further using different viral strains. In that regard, we previously HMPV strains harbor distinct in vitro fusogenic and vivo pathogenic phenotypes, possibly influencing the selection of vaccine study, investigated putative contribution low conserved accessory proteins such strain-dependent phenotypes generated recombinant wild type (WT) SH- G-deleted viruses derived from two patient-derived strains, A1/C-85473 B2/CAN98-75. The ΔSH ΔG deletions led strain-specific both LLC-MK2 cell reconstituted human airway epithelium models. More interestingly, ΔG-85473 especially ΔSH-C-85473 conferred significant protection against challenge induced immunogenicity heterologous strain. conclusion, our results show genetic backbone should be considered design vaccines, SH-deleted virus strain could LAV candidate as it attenuated protective mice while being efficiently produced cell-based system.