Successful Treatment of Ebola Virus–Infected Cynomolgus Macaques with Monoclonal Antibodies

Abstract

Macaques survived infection with Ebola virus when treated starting at 24 hours after infection with mix of three neutralizing monoclonal antibodies.

Delayed treatment of Ebola virus infection with plant-derived monoclonal antibodies provides protection in rhesus macaques

“…The importance of antibodies in the adaptive immune response during vaccination is well recognized, and the use of antibodies as therapeutics against infectious disease is building credibility as well (6,28,29). It is only recently, however, that passive immunization for EBOV-with macaque polyclonal IgG and with mouse mAbshas been demonstrated (20,21). The results presented here further extend these findings to a mixture of mAbs appropriate for human administration.…”

“…As an approach to develop a mAb-based medical countermeasure, Marzi et al (18) demonstrated that two neutralizing mouse/human chimeric mAbs against EBOV could provide limited protection in rhesus macaques (one of three animals survived) when dosing was initiated 24 h before challenge (1,000 pfu ∼1,000 LD 50 ). More recently, Qiu et al (21) found a mixture of neutralizing murine mAbs could protect cynomolgus macaques when given 1 (four of four survived) or 2 d p.i. (two of four survived).…”

Post-exposure treatments for Ebola and Marburg virus infections

“…Each group used a different cocktail of three mouse mAbs targeting the EBOV GP, administered beginning either 1 day or 2 days after EBOV (Kikwit strain) challenge. Qiu et al 138 used a pool of three mouse mAbs (1H3, 2G4 and 4G7), designated as ZMAb, and demonstrated 50-100% protection (depending on dosing schedule) after EBOV infection of cynomolgus monkeys. Olinger et al 139 used a pool of three mouse-human chimeric mAbs (13C6, 13F6 and 6D8), designated MB-003, and demonstrated 67% protection (two of three animals) after EBOV infection of rhesus monkeys.…”

Codon-optimized filovirus DNA vaccines delivered by intramuscular electroporation protect cynomolgus macaques from lethal Ebola and Marburg virus challenges

“…18 In addition, 2 groups showed partial protection of NHP following treatment with mAbs up to 24 hr post infection, 42,43 and another group reported complete protective immunity with a cocktail of mAbs. 19 In past human outbreaks, convalescent sera were used to treat infected patients of sporadic outbreaks of filoviruses with suggestive evidence for increased survival. 44,45 In the current outbreak, a cocktail of 3 MAbs (ZMapp, Mapp Biopharmaceutical, Inc., San Diego, CA), which is produced in tobacco plants, 46 has been used to treat infected medical workers.…”

“…In general, both strong humoral and cell-mediated immune responses have been shown to be important for survival from filovirus infections. [17][18][19][20][21] In earlier studies, we showed that DNA vaccines expressing the GP genes of MARV delivered by gene gun elicited partially protective immunity in NHP. 22 Similarly, we showed that an EBOV GP DNA vaccine delivered to guinea pigs by gene gun provided partial protection against EBOV challenge.…”