Longitudinal proteome-wide antibody profiling in Marburg virus survivors identifies wing domain immunogen for vaccine design.

Few data exist on the quality of polyclonal antibody responses generated following MARV infection of survivors and its evolution over time. In this report, the researchers analyzed MARV proteome-wide antibody repertoire longitudinally for five years post MARV infection approximately every six months in ten human survivors during the convalescent phase. IgM vs. IgG vs. IgA epitope diversity, antibody binding, antibody affinity maturation, and Fc-receptor interaction to MARV proteins revealed differential kinetics. MARV-neutralizing antibody durability is poor in survivors. MARV infection elicits a broad epitope repertoire covering GP, VP40, VP30, and VP24 dominant responses persisting up to 5 years after MARV exposure. However, with time, the IgM and IgA repertoire decreases. IgG-recognizing antigenic sites mainly in the amino-terminus, wing domain, and GP2-heptad repeat are made from MARV-GP. Notably, MARV infection induces strong long-lived FcɣRI, FcɣRIIA, and FcɣRIIIA IgG-Fc receptor pairings. Unconventional neutralizing antibodies against MARV are induced by immunization with the immunodominant MARV epitopes, exposing the conserved wing region between GP1 and GP2. previously, it was noted that MARV infection bestows a diverse, long persistent, non-neutralizing, IgG antibody repertoire that disturbs disease by fcɣr activity. These findings, in addition to identifying neutralizing immunogens within the wing domain, can facilitate the rational engineering of effective therapeutics and vaccines against the Marburg virus.
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