National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
R01 AI13752
米国
引用
ジャーナル: Nat Microbiol / 年: 2024 タイトル: Functional and structural basis of human parainfluenza virus type 3 neutralization with human monoclonal antibodies. 著者: Naveenchandra Suryadevara / Ana Rita Otrelo-Cardoso / Nurgun Kose / Yao-Xiong Hu / Elad Binshtein / Rachael M Wolters / Alexander L Greninger / Laura S Handal / Robert H Carnahan / Anne ...著者: Naveenchandra Suryadevara / Ana Rita Otrelo-Cardoso / Nurgun Kose / Yao-Xiong Hu / Elad Binshtein / Rachael M Wolters / Alexander L Greninger / Laura S Handal / Robert H Carnahan / Anne Moscona / Theodore S Jardetzky / James E Crowe / 要旨: Human parainfluenza virus type 3 (hPIV3) is a respiratory pathogen that can cause severe disease in older people and infants. Currently, vaccines against hPIV3 are in clinical trials but none have ...Human parainfluenza virus type 3 (hPIV3) is a respiratory pathogen that can cause severe disease in older people and infants. Currently, vaccines against hPIV3 are in clinical trials but none have been approved yet. The haemagglutinin-neuraminidase (HN) and fusion (F) surface glycoproteins of hPIV3 are major antigenic determinants. Here we describe naturally occurring potently neutralizing human antibodies directed against both surface glycoproteins of hPIV3. We isolated seven neutralizing HN-reactive antibodies and a pre-fusion conformation F-reactive antibody from human memory B cells. One HN-binding monoclonal antibody (mAb), designated PIV3-23, exhibited functional attributes including haemagglutination and neuraminidase inhibition. We also delineated the structural basis of neutralization for two HN and one F mAbs. MAbs that neutralized hPIV3 in vitro protected against infection and disease in vivo in a cotton rat model of hPIV3 infection, suggesting correlates of protection for hPIV3 and the potential clinical utility of these mAbs.
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D: Heavy chain Fab rPIV3-18 E: Light chain Fab rPIV3-28 F: Heavy chain Fab rPIV3-18 G: Light chain Fab rPIV3-28 H: Heavy chain Fab rPIV3-18 L: Light chain Fab rPIV3-28 A: Fusion glycoprotein F0 B: Fusion glycoprotein F0 C: Fusion glycoprotein F0