Pan-neutralization of parainfluenza viruses by a hemagglutinin-neuraminidase antibody

Abstract

Human parainfluenza viruses (HPIVs) can cause severe respiratory illnesses, such as croup, bronchiolitis, and pneumonia, particularly in children, the elderly and immunocompromised individuals. No vaccines or specific therapeutics are available for use in humans. Here, we report the discovery of a human monoclonal antibody designated PVA269 that broadly and potently neutralizes all four HPIV subtypes, PIV5, and Sendai virus by targeting the hemagglutinin-neuraminidase (HN) glycoprotein. We show that PVA269 inhibits neuraminidase activity and hemagglutination of erythrocytes through insertion of a long heavy chain complementary-determining region 3 in the enzyme active site. We reveal that the antibody markedly remodels its interactions to accommodate distinct viral features across HPIV subtypes, such as HPIV2 N-linked glycans. These results define the molecular basis for the unique PVA269 pan-neutralizing activity of human and animal viruses spanning two genera. PVA269 provides potent prophylactic activity against HPIV3 replication in the upper and lower airways of the clinically predictive cotton rat model, thus supporting translation of its protective efficacy to humans. These data establish PVA269 as a best-in-class monoclonal antibody and a promising clinical candidate to prevent HPIV infection, transmission, and disease in vulnerable populations.

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BibTeX RIS

BibTeX

@misc{marco2026panneutralization,
  title = {{Pan-neutralization of parainfluenza viruses by a hemagglutinin-neuraminidase antibody}},
  author = {A. De Marco and R. Gen and Y.-J. Park and G. Cusumano and C. Gibson and S. Vyas and C. Momont and F. Tasin and S. C. Galli and B. Merz and I. Giacchetto-Sasselli and E. Vetti and T. Reitz and B. Tsu and K. Yim and J. Blanco and R. Piantanida and N. Czudnochowski and J. L. Miller and G. Snell and M. S. Boukhvalova and J. E. Towne and D. Corti and M. S. Pizzuto and D. Veesler},
  howpublished = {bioRxiv},
  year = {2026},
  month = sep,
  doi = {10.64898/2026.09.07.749649},
  url = {https://www.biorxiv.org/content/10.64898/2026.09.07.749649v1},
  note = {CC BY},
}

RIS

TY  - UNPB
TI  - Pan-neutralization of parainfluenza viruses by a hemagglutinin-neuraminidase antibody
AU  - A. De Marco
AU  - R. Gen
AU  - Y.-J. Park
AU  - G. Cusumano
AU  - C. Gibson
AU  - S. Vyas
AU  - C. Momont
AU  - F. Tasin
AU  - S. C. Galli
AU  - B. Merz
AU  - I. Giacchetto-Sasselli
AU  - E. Vetti
AU  - T. Reitz
AU  - B. Tsu
AU  - K. Yim
AU  - J. Blanco
AU  - R. Piantanida
AU  - N. Czudnochowski
AU  - J. L. Miller
AU  - G. Snell
AU  - M. S. Boukhvalova
AU  - J. E. Towne
AU  - D. Corti
AU  - M. S. Pizzuto
AU  - D. Veesler
PY  - 2026
DA  - 2026/09/07
PB  - bioRxiv
DO  - 10.64898/2026.09.07.749649
UR  - https://www.biorxiv.org/content/10.64898/2026.09.07.749649v1
AB  - Human parainfluenza viruses (HPIVs) can cause severe respiratory illnesses, such as croup, bronchiolitis, and pneumonia, particularly in children, the elderly and immunocompromised individuals. No vaccines or specific therapeutics are available for use in humans. Here, we report the discovery of a human monoclonal antibody designated PVA269 that broadly and potently neutralizes all four HPIV subtypes, PIV5, and Sendai virus by targeting the hemagglutinin-neuraminidase (HN) glycoprotein. We show that PVA269 inhibits neuraminidase activity and hemagglutination of erythrocytes through insertion of a long heavy chain complementary-determining region 3 in the enzyme active site. We reveal that the antibody markedly remodels its interactions to accommodate distinct viral features across HPIV subtypes, such as HPIV2 N-linked glycans. These results define the molecular basis for the unique PVA269 pan-neutralizing activity of human and animal viruses spanning two genera. PVA269 provides potent prophylactic activity against HPIV3 replication in the upper and lower airways of the clinically predictive cotton rat model, thus supporting translation of its protective efficacy to humans. These data establish PVA269 as a best-in-class monoclonal antibody and a promising clinical candidate to prevent HPIV infection, transmission, and disease in vulnerable populations.
ER  -

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