The human B cell response to natural
filovirus infections early after recovery is poorly understood. Previous serologic studies suggest that some Ebola virus survivors exhibit delayed antibody responses with low magnitude and quality. Here, we sought to study the population of individual memory B cells induced early in
convalescence. We isolated
monoclonal antibodies (MAbs) from memory B cells from four survivors treated for
Ebola virus disease (EVD) 1 or 3 months after discharge from the hospital. At the early time points postrecovery, the frequency of Ebola-specific B cells was low and dominated by clones that were cross-reactive with both Ebola
glycoprotein (GP) and with the secreted GP (sGP) form. Of 25 MAbs isolated from four donors, only one exhibited neutralization activity. This neutralizing MAb, designated MAb EBOV237, recognizes an
epitope in the
glycan cap of the
surface glycoprotein. In vivo murine lethal challenge studies showed that EBOV237 conferred protection when given prophylactically at a level similar to that of the
ZMapp component MAb 13C6. The results suggest that the human B cell response to EVD 1 to 3 months postdischarge is characterized by a paucity of broad or potent neutralizing clones. However, the neutralizing
epitope in the
glycan cap recognized by EBOV237 may play a role in the early human antibody response to EVD and should be considered in rational design strategies for new
Ebola virus vaccine candidates.IMPORTANCE The pathogenesis of
Ebola virus disease (EVD) in humans is complex, and the mechanisms contributing to immunity are poorly understood. In particular, it appears that the quality and magnitude of the human B cell response early after recovery from EVD may be reduced compared to most
viral infections. Here, we isolated human
monoclonal antibodies from B cells of four survivors of EVD at 1 or 3 months after hospital discharge. Ebola-specific memory B cells early in
convalescence were low in frequency, and the
antibodies they encoded demonstrated poor neutralizing potencies. One
neutralizing antibody that protected mice from lethal
infection, EBOV237, was identified in the panel of 25 human
antibodies isolated. Recognition of the
glycan cap
epitope recognized by EBOV237 suggests that this antigenic site should be considered in
vaccine design and treatment strategies for EVD.