Affiliations: [a] Mapp Biopharmaceutical, Inc. San Diego, CA, USA | [b] National Laboratory for Zoonotic Diseases and Special Pathogens, Public Health Agency of Canada, Winnipeg, MB, Canada
Correspondence:
[*]
Corresponding author: Andrew Hiatt, Mapp Biopharmaceutical, Inc. San Diego, CA, USA. E-mail:andy.hiatt@mappbio.com
Abstract: This review describes the history of Ebola monoclonal antibody (mAb)
development leading up to the recent severe Ebola outbreak in West Africa.
The Ebola virus has presented numerous perplexing challenges in the long
effort to develop therapeutic antibody strategies. Since the first report of
a neutralizing human anti-Ebola mAb in 1999, the straightforward progression
from in vitro neutralization resulting in in vivo protection
and therapy has not occurred. A number of mAbs, including the first reported,
failed to protect non-human primates (NHPs) in spite of protection in rodents.
An appreciation of the
role of effector functions to antibody efficacy has contributed
significantly to understanding mechanisms of in vivo protection. However a crucial
contribution, as measured by post-exposure therapy of NHPs, involved the
comprehensive testing of mAb cocktails. This effort was aided by the use of
plant production technology where various combinations of mAbs could be
rapidly produced and tested. Introduction of appropriate modifications, such
as specific glycan profiles, also improved therapeutic efficacy. The
resulting cocktail, ZMapp™, consists of three mAbs that were
identified from numerous mAb candidates. ZMapp™ \ is now being
evaluated in human clinical trials but has already played a role in bringing
awareness to the potential of antibody therapy for Ebola.
