2. Academic Validation
  3. Functional and structural basis of human parainfluenza virus type 3 neutralization with human monoclonal antibodies

Functional and structural basis of human parainfluenza virus type 3 neutralization with human monoclonal antibodies

  • Nat Microbiol. 2024 Jun 10. doi: 10.1038/s41564-024-01722-w.
Naveenchandra Suryadevara # 1,  Ana Rita Otrelo-Cardoso # 2,  Nurgun Kose 1,  Yao-Xiong Hu 2,  Elad Binshtein 1,  Rachael M Wolters 1,  Alexander L Greninger 3,  Laura S Handal 1,  Robert H Carnahan 1 4,  Anne Moscona 5,  Theodore S Jardetzky 6,  James E Crowe Jr 7 8 9
Affiliations

Affiliations

  • 1 Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN, USA.
  • 2 Department of Structural Biology, Stanford University School of Medicine, Stanford, CA, USA.
  • 3 Department of Laboratory Medicine and Pathology, University of Washington Medical Center, Seattle, WA, USA.
  • 4 Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, USA.
  • 5 Departments of Pediatrics, Microbiology and Immunology, and Physiology and Cellular Biophysics, and Center for Host-Pathogen Interaction, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA.
  • 6 Department of Structural Biology, Stanford University School of Medicine, Stanford, CA, USA. tjardetz@stanford.edu.
  • 7 Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN, USA. james.crowe@vumc.org.
  • 8 Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, USA. james.crowe@vumc.org.
  • 9 Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA. james.crowe@vumc.org.
  • # Contributed equally.
PMID: 38858594 DOI: 10.1038/s41564-024-01722-w
Abstract

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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