Longitudinal proteome-wide antibody profiling in Marburg virus survivors identifies wing domain immunogen for vaccine design
Khurana S, Grubbs G, Ravichandran S, Cluff E, Kim J, Kuehne AI, Zak S, Dye JM, Lutwama JJ, Herbert AS
Applications: SPR
Reactive species: Human
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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."
Article snippet: Recombinant Marburg virus-like particles (VLPs expressing MARV trimeric GP on surface of particles made of MARV matrix proteins VP40 and NP), and
MARV GP,
NP, VP35, VP40, VP24, VP30 and L polymerase proteins were purchased from *, *, and Creative Diagnostics Inc.
Figure 1. Longitudinal SPR based analysis of MVD survivor plasma against purified recombinant MARV proteins.
Figure 2. Antibody affinity maturation of MVD survivor plasma against MARV proteome.