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Cross-protective antibodies against common endemic respiratory viruses.
Cabán, Madelyn; Rodarte, Justas V; Bibby, Madeleine; Gray, Matthew D; Taylor, Justin J; Pancera, Marie; Boonyaratanakornkit, Jim.
Afiliación
  • Cabán M; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
  • Rodarte JV; Department of Immunology & Department of Global Health, University of Washington, Seattle, WA, USA.
  • Bibby M; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
  • Gray MD; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
  • Taylor JJ; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
  • Pancera M; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA. jtaylor3@fredhutch.org.
  • Boonyaratanakornkit J; Department of Immunology & Department of Global Health, University of Washington, Seattle, WA, USA. jtaylor3@fredhutch.org.
Nat Commun ; 14(1): 798, 2023 02 13.
Article en En | MEDLINE | ID: mdl-36781872
Respiratory syncytial virus (RSV), human metapneumovirus (HMPV), and human parainfluenza virus types one (HPIV1) and three (HPIV3) can cause severe disease and death in immunocompromised patients, the elderly, and those with underlying lung disease. A protective monoclonal antibody exists for RSV, but clinical use is limited to high-risk infant populations. Hence, therapeutic options for these viruses in vulnerable patient populations are currently limited. Here, we present the discovery, in vitro characterization, and in vivo efficacy testing of two cross-neutralizing monoclonal antibodies, one targeting both HPIV3 and HPIV1 and the other targeting both RSV and HMPV. The 3 × 1 antibody is capable of targeting multiple parainfluenza viruses; the MxR antibody shares features with other previously reported monoclonal antibodies that are capable of neutralizing both RSV and HMPV. We obtained structures using cryo-electron microscopy of these antibodies in complex with their antigens at 3.62 Å resolution for 3 × 1 bound to HPIV3 and at 2.24 Å for MxR bound to RSV, providing a structural basis for in vitro binding and neutralization. Together, a cocktail of 3 × 1 and MxR could have clinical utility in providing broad protection against four of the respiratory viruses that cause significant morbidity and mortality in at-risk individuals.
Asunto(s)

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Virus Sincitial Respiratorio Humano / Infecciones por Virus Sincitial Respiratorio / Infecciones por Paramyxoviridae / Metapneumovirus Límite: Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Virus Sincitial Respiratorio Humano / Infecciones por Virus Sincitial Respiratorio / Infecciones por Paramyxoviridae / Metapneumovirus Límite: Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos