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.
(HW)
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