2023年7月18日火曜日

Cross-protective antibodies against common endemic respiratory viruses

 Respiratory syncytial virus (RSV), human metapneumovirus (HMPV), and human parainfluenza virus types one (HPIV1) and three (HPIV3) pose major problems as it causes pneumonia and bronchiolitis in at-risk individuals including infants and immunocompromised adults. Additionally, pathogenic viruses in adults are diversity, so cross-protective mAbs neutralising these viruses could serve as an alternative way for attaining a wider population against respiratory viral infections.  
  In this study, two cross-protective neutralizing mAb, namely 3X1 (targeting HPIV3 and HPIV1) and MXR (targeting RSV and HMPV) were discovered by labelled viral fusion protein. 3X1 mAb was discovered by a bait-and-switch strategy involved the isolation of HPIV3 preF tetramer-marked human splenocytes capable of neutralising with HPIV1, selecting the neutralizing mAb binding to specific region of both HPIV1 and HPIV3. MXR mAb were obtained by isolating from single isotype-switched B cells that contained specific alleles for heavy and light chain and bind to F proteins of RSV and HMPV. It proved that both 3X1 and MXR mAbs effectively neutralized the targeted viruses in vitro and in vivo. Analysis with cryo-electron microscopy allowed to identify specific binding neutralizing region in antigen. Furthermore, a cocktail combing 3X1 and MXR mAbs exhibited cross-protective neutralizing ability against these viruses in mice. 

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