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Longitudinal proteome-wide antibody profiling in Marburg virus survivors identifies wing domain immunogen for vaccine design
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Longitudinal proteome-wide antibody profiling in Marburg virus survivors identifies wing domain immunogen for vaccine design
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Journal Article
Longitudinal proteome-wide antibody profiling in Marburg virus survivors identifies wing domain immunogen for vaccine design
2024
Overview
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.
One sentence summary
Longitudinal Marburg virus human antibody repertoire
There is limited understanding of long-term antibody dynamics after Marburg virus infection. Here, Khurana et al report the antibody responses in Marburg virus disease survivors over five years and identify a conserved immunogen within the virus wing domain that could serve as a target for vaccine design.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 49/47
/ 49/75
/ 82/1
/ 82/103
/ 82/47
/ 82/79
/ 82/83
/ Adult
/ Antibodies, Neutralizing - immunology
/ Antibodies, Viral - immunology
/ Epitopes
/ Female
/ Humanities and Social Sciences
/ Humans
/ Immunoglobulin A - immunology
/ Immunoglobulin G - immunology
/ Immunoglobulin M - immunology
/ Male
/ Marburg Virus Disease - immunology
/ Marburg Virus Disease - virology
/ Science
/ Survival
/ Vaccines
/ Viral Envelope Proteins - immunology
/ Viruses
