Wednesday, November 05, 2014

Ebola-2014: Still in news


   In less than a couple of months, Ebola has become the search term of interest and is currently the most focused component of concern. And rightly so. It has been accused by many that there are no readily approved treatment or vaccines against this infection. But it is to be understood that scientists don't work like magic. Science needs its own time to make discoveries. But then scientists are working out of their way to bring in promising results.

    The current outbreak is perplexing, given its unprecedented geographical distribution and number of cases involved. As per the estimates the total number of reported cases is more than 13500 and deaths nearing 5000. Liberia alone has 6,500 cases and 2,413 deaths reported as of Oct. 31. And then there will be a set of unreported cases. Models have estimated a very high number of total cases which includes reported and unreported cases. However, its debatable if the models are over estimating the current prevalence and incidence.

     Other than the Zmapp, and a couple of experimental drugs (Link) which in itself is under testing phase, there is not much available in the hands to counter the current outbreak. This provides the most attractive time to come up with anything novel. As I have previously discussed in this blog vaccine is perhaps the best candidate (Link). However, only a vector vaccine containing replication competent VSV (Vesicular stomatitis virus) carrying Ebola Glycoprotein has shown to be of some use. The other well explored area is use of adenovirus carrying antigens as a vaccine. In a recently published hot paper- this has been used in the form of nasal spray, promising to provide long-term immunity.

    This isn't actually a new discovery. Literature has been published on this by Maria Croyle and team in 2006 (Link), showing that nasal delivery of Adenovirus Expressing the Ebola Glycoprotein conferred protection in a mice model. The vaccine basically consists of human adenovirus serotype 5 (AdHu5) expressing the wild-type ZEBOV glycoprotein sequence from a CMV promoter. This combination is called Ad-CMVZGP. The new study by Croyle and team showed that the vaccine elicited good immune response, through Intra nasal route in comparison with other routes. The protection was demonstrated 21 weeks after immunization.

   The study offers great advantages, as one of the author in study says "The main advantage of our vaccine platform over the others in clinical testing is the long-lasting protection after a single intranasal dose. This is important since the longevity of other vaccines for Ebola that are currently being evaluated is not fully understood. Moreover, the nasal spray immunization method is more attractive than a needle vaccine given the costs associated with syringe distribution and safety." Source

   Another vaccine that has promising pre clinical data ChAd-Ebola; Chimpanzee-Adenovirus chAD3-ZEBOV. The Phase I trial is expected to be initiated at the earliest and results will be available by early 2015.

The current outbreak has exposed the unpreparedness to counter the Ebola. As I always say, basic biology needs to be done. But, then there is a great support to come up with defense mechanism that may help us be prepared at least the next time. And the question of prospects of the vaccine, only the next set of data will tell.
Croyle, M., Feldmann, H., Jones, S., Wilson, J., & Kobinger, G. (2006). 595. Nasal Delivery of Adenovirus Expressing the Ebola Glycoprotein Protects Mice Against Ebola Virus in the Presence of Preexisting Immunity to the Vaccine Carrier. Molecular Therapy, 13 DOI: 10.1016/j.ymthe.2006.08.669

Richardson JS, Yao MK, Tran KN, Croyle MA, Strong JE, Feldmann H, & Kobinger GP (2009). Enhanced protection against Ebola virus mediated by an improved adenovirus-based vaccine. PloS one, 4 (4) PMID: 19390586

Choi, J., Jonsson-Schmunk, K., Qiu, X., Shedlock, D., Strong, J., Xu, J., Michie, K., Audet, J., Fernando, L., Myers, M., Weiner, D., Bajrovic, I., Tran, L., Wong, G., Bello, A., Kobinger, G., Schafer, S., & Croyle, M. (2014). A Single Dose Respiratory Recombinant Adenovirus-Based Vaccine Provides Long-Term Protection for Non-Human Primates from Lethal Ebola Infection. Molecular Pharmaceutics DOI: 10.1021/mp500646d

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