, 2004 and Guillaume et al , 2006) Presently, the only reported

, 2004 and Guillaume et al., 2006). Presently, the only reported and effective post-exposure therapy against Hendra or Nipah virus infection and one that could likely be approved in the near future for use in people has been a human monoclonal antibody (mAb) known as m102.4 which was isolated from a recombinant naïve human phage-displayed Fab library (Zhu et al., 2008). The m102.4 mAb has exceptionally potent neutralizing activity against both Nipah and Hendra viruses and its epitope maps to the ephrin receptor binding site (Fig. 1). Testing of m102.4 has confirmed its neutralization activity Z-VAD-FMK order against several isolates; NiV-Malaysia, HeV-1994, HeV-Redlands, NiV-Bangladesh

(Bossart et al., 2009). Effective post-exposure efficacy with m102.4 has now been demonstrated in both ferrets and nonhuman primates (African green monkey (AGM)) infected with Pictilisib in vitro either Hendra virus or Nipah virus

(Table 1). The successful m102.4 passive immunotherapy in the AGM was recently reported in a study designed to reflect a possible real life scenario requiring mAb as a post-exposure treatment, and was a follow-up from the initial successful m102.4 post-exposure therapy carried out in ferrets (Bossart et al., 2009). Fourteen monkeys were challenged intratracheally with Hendra virus and 12 animals were infused twice with a 100 mg dose (∼20 mg/kg) of m102.4 beginning at 10 h, 24 h or 72 h p.i. with the second infusion ∼48 h later. All 12 animals that received m102.4 survived infection; whereas the untreated control subjects succumbed to severe systemic disease by day 8 (Bossart et al., 2011). There was no evidence of Hendra virus mediated pathology in any of the m102.4-treated animals and no infectious Hendra virus could be recovered from any tissues from any m102.4-treated subjects. In May of 2010,

an instance of possible Hendra Thymidine kinase virus infection in two individuals was reported on the Sunshine Coast, north of Brisbane, Australia. Both individuals had extensive close contact with a horse just prior to and during the development of clinical illness in the animal. Following a diagnosis of Hendra virus infection in the horse, both individuals were considered to have had high-risk exposure to Hendra virus (Anonymous, 2010). A request was made by Australian health authorities to obtain m102.4 as a possible compassionate use therapeutic option even though clinical trials in human had not been undertaken and safety data of the mAb in humans was lacking. These two individuals were administered the m102.4 mAb (Miles, 2010). Both individuals ultimately did not develop detectable Hendra virus infection but whether this was due to the mAb therapy could not be determined. In 2010, the cell line expressing the human m102.4 mAb was provided to the Queensland Government, Queensland Health, to allow health authorities to manufacture m102.4 for its potential use on a compassionate basis in future cases of high-risk human exposure.

Leave a Reply

Your email address will not be published. Required fields are marked *


You may use these HTML tags and attributes: <a href="" title=""> <abbr title=""> <acronym title=""> <b> <blockquote cite=""> <cite> <code> <del datetime=""> <em> <i> <q cite=""> <strike> <strong>