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Longitudinal proteome-wide antibody profiling in Marburg virus survivors identifies wing domain immunogen for vaccine design.
Khurana, Surender; Grubbs, Gabrielle; Ravichandran, Supriya; Cluff, Emily; Kim, JungHyun; Kuehne, Ana I; Zak, Samantha; Dye, John M; Lutwama, Julius J; Herbert, Andrew S.
Afiliación
  • Khurana S; Division of Viral Products, Center for Biologics Evaluation and Research (CBER), FDA, Silver Spring, MD, 20993, USA. Surender.Khurana@fda.hhs.gov.
  • Grubbs G; Division of Viral Products, Center for Biologics Evaluation and Research (CBER), FDA, Silver Spring, MD, 20993, USA.
  • Ravichandran S; Division of Viral Products, Center for Biologics Evaluation and Research (CBER), FDA, Silver Spring, MD, 20993, USA.
  • Cluff E; Division of Viral Products, Center for Biologics Evaluation and Research (CBER), FDA, Silver Spring, MD, 20993, USA.
  • Kim J; Division of Viral Products, Center for Biologics Evaluation and Research (CBER), FDA, Silver Spring, MD, 20993, USA.
  • Kuehne AI; Virology Division, U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD, USA.
  • Zak S; Virology Division, U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD, USA.
  • Dye JM; Virology Division, U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD, USA.
  • Lutwama JJ; Department of Arbovirology, Emerging, and Re-emerging Infection, Uganda Virus Research Institute, Entebbe, Uganda.
  • Herbert AS; Virology Division, U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD, USA.
Nat Commun ; 15(1): 8133, 2024 Sep 17.
Article en En | MEDLINE | ID: mdl-39285186
ABSTRACT
Limited knowledge exists on the quality of polyclonal antibody responses generated following Marburg virus (MARV) infection and its evolution in survivors. In this study, we evaluate MARV proteome-wide antibody repertoire longitudinally in convalescent phase approximately every six months for five years following MARV infection in ten human survivors. Differential kinetics were observed for IgM vs IgG vs IgA epitope diversity, antibody binding, antibody affinity maturation and Fc-receptor interaction to MARV proteins. Durability of MARV-neutralizing antibodies is low in survivors. MARV infection induces a diverse epitope repertoire with predominance against GP, VP40, VP30 and VP24 that persisted up to 5 years post-exposure. However, the IgM and IgA repertoire declines over time. Within MARV-GP, IgG recognize antigenic sites predominantly in the amino-terminus, wing domain and GP2-heptad repeat. Interestingly, MARV infection generates robust durable FcɣRI, FcɣRIIA and FcɣRIIIA IgG-Fc receptor interactions. Immunization with immunodominant MARV epitopes reveals conserved wing region between GP1 and GP2, induces neutralizing antibodies against MARV. These findings demonstrate that MARV infection generates a diverse, long-lasting, non-neutralizing, IgG antibody repertoire that perturbs disease by FcɣR activity. This information, along with discovery of neutralizing immunogen in wing domain, could aid in development of effective therapeutics and vaccines against Marburg virus.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteoma / Anticuerpos Neutralizantes / Marburgvirus / Enfermedad del Virus de Marburg / Anticuerpos Antivirales Límite: Adult / Female / Humans / Male / Middle aged Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
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XML
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteoma / Anticuerpos Neutralizantes / Marburgvirus / Enfermedad del Virus de Marburg / Anticuerpos Antivirales Límite: Adult / Female / Humans / Male / Middle aged Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido