ZMapp and Ebola

492027539ZMapp is the name of a treatment that's been tested in our close cousins, monkeys, that's offering the only hope so far that we may be able to make some headway against Ebola virus (EBOV) infection, Rick and I discuss on PodMed this week. And while we almost never feature studies limited to non-human primates, or things published in Nature, in this case the public health import is so great we've made an exception. Thank you, monkeys!

Previous research on treatments for Ebola virus infection identified two combinations of monoclonal antibodies that looked promising:  the monoclonal antibody cocktail MB-003, consisting of human or human–mouse chimeric antibodies, and ZMAb, consisting of mouse antibodies. When these were administered after Ebola virus infection more than 24 hours previously, they still demonstrated substantial benefit. The current paper aimed to optimize the combination of these two cocktails and determine what the authors call the "therapeutic limit."

The mouse antibodies were humanized, multiple combinations of antibodies were screened in guinea pigs and Rhesus monkeys, with the animals challenged with the virus and survival noted. The optimal combination was administered to monkeys up to five days post-infection with the Guinean variant of the virus, the one currently in circulation in Africa. Eleven of twelve monkeys had both fever and detectable virus in their blood, indicating that the antibody cocktail was therapeutic rather than prophylactic. ZMapp was able to reverse severe EBOV disease as indicated by elevated liver enzymes, mucosal haemorrhages and rash in a few animals.

This is of course, the self-same cocktail of antibodies that was administered to two American workers who were infected and became quite ill with EBOV, both of whom survived. The authors note that such antibody cocktails, (and I bow here to colleagues who've vociferously corrected me on the use of 'cocktail,' implying as it does fun times and socializing, which couldn't be further from the truth with regard to infections associated with a high degree of mortality), are much less problematic clinically than antibody purified from convalescent humans, easier to scale up, and useful across the age spectrum.  In view of the patent fact that so far, containment efforts underway in Africa have sadly failed, with CDC and WHO folks predicting somewhere between 20,000 and 100,000 new infections before things damp down, seems the most compassionate strategy to get large-scale manufacturing underway as soon as possible. Rick predicts that ZMapp will likely have a role in the armamentarium even as a vaccine is developed, since there will always be a population in whom the vaccine fails to elicit a protective immune response. Having been to sub-Saharan Africa myself, it also seems likely that even highly publicized vaccination efforts are likely to miss quite a few people who would then remain susceptible to infection.  But thank God at least that vaccine development, as announced by the NIH this week, is also underway.

Other topics this week include two from NEJM: a novel agent in the management of congestive heart failure and the usefulness of flu vaccination in pregnant women, both HIV positive and HIV negative, and in the Lancet, beta blockers in people with congestive heart failure and atrial fibrillation.  Until next week, y'all live well.

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