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Combating Ebola Virus with Antibodies – An interview with Dr. Larry Zeitlin

By So-Un Kim

MB-003 and its affect on Ebola virus

The post-exposure efficacy of MB-003 Monoclonal Antibody Cocktail on Ebola virus infected Rhesus macaques

Focal Paper: Therapeutic Intervention of Ebola Virus Infection in Rhesus Macaques with the MB-003 Monoclonal Antibody Cocktail by James Pettitt et al.

   The Ebola virus, first discovered in 1976 in Central Africa, is among the most virulent infectious agents known and has an extremely high case-fatality rate. There has been no treatment or cure that has been effective against the Ebola virus, and with the potential ability to turn Ebola into a bio-weapon, it is labeled as Risk Group 4 Pathogen. Much scientific research has been invested in trying to better understand the effect of viral infection on the human body in order to discover an effective treatment.

By 2011, researchers engineered plants to produce an anti-Ebola virus monoclonal antibodies resulting in a glycosylation profile with greater homogeneity, in hopes to find preventative solutions to the Ebola virus infection. In 2013, a cocktail of three monoclonal antibodies manufactured in Nicotiana benthamiana was tested, which proved 100% effective when administered within 24 hours in non-human primates.

In the focal paper, the researchers tested the post-exposure efficacy in rhesus macaques. They set up an experiment where seven rhesus macaques were infected with Ebola virus. The researchers made sure to wait until both the fever and a positive reverse transcription polymerase chain reaction (PCR) were present before administrating the treatment cocktail. Out of the seven rhesus macaques that received treatment, three survived, which is a much higher survival compared to the usual 88%-90% case-fatality of the Ebola virus diseased patients.

I interviewed Dr. Larry Zeitlin , one of the main scientist in charge of this study. Dr. Zeitlin is president of Mapp Biopharmaceuticals, and started studying Ebola virus when he was offered funding from Defense Advanced Research Projects Agency in 2002.

 1. How did the idea to test MB-003’s effectiveness post infection come about?

This was driven by funding agencies.They wanted post-exposure efficacy rather than prophylactic protection.

 2. You took part in many studies regarding Ebola virus. Do you believe there has been much progress in the production of a viable antibody that could be used as a cure?

Yes, when you consider before 2012 no one had shown that antibodies could protect a monkey and now multiple groups have done so.

3. There must have been many obstacles and frustrations during research. I believe MB-003 took a long time to come up with. How did you get past the obstacles and frustrations?

Time and patience – drug development is almost always a slow process.

4. Was there a moment in any research you have done that was a defining moment for you or that you believed was a great accomplishment?

Showing that monoclonal can work against Ebola therapeutically (after symptoms are present) was a big moment for me.

5. How and when did you start developing interest in science and research?

I’ve been interested in science since I was a child.

6. What is your future plan in the scientific field in general as well as the research being done on the Ebola virus?

We’re applying the same concepts of using monoclonals for a whole range of infectious diseases.

 

James Pettitt, Larry Zeitlin, Do H. Kim, Cara Working, Joshua C. Johnson, Ognian Bohorov, Barry Bratcher, Ernie Hiatt, Steven D. Hume, Ashley K. Johnson, Josh Morton, Michael H. Pauly, Kevin J. Whaley, Michael F. Ingram, Ashley Zovanyi, Megan Heinrich, Ashley Piper, Justine Zelko, and Gene G. Olinger, Therapeutic Intervention of Ebola Virus Infection in Rhesus Macaques with the MB-003 Monoclonal Antibody Cocktail, Proc. Natl. Acad. Sci. U.S.A. 199, 113-199 (2013).

http://stm.sciencemag.org/content/5/199/199ra113.full

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