Monday, March 24, 2014

Ebola in Southern Guinea: Vaccine Candidates for Ebola

01 - Ebola_Infographic_130713



Update: WHO reports Conakry tests have come back negative (see: http://www.bbc.com/news/world-africa-26717490), a bit difficult to believe that the French lab would have been in error. If the samples are negative, it will be interesting to see the results. 


Although  several African nations suffer endemic Ebola outbreaks, no vaccine currently exists to prevent or treat victims of this hemorrhagic fever. The recent outbreak of Ebola in Guinea has killed 59 of the 80 people reported to have contracted it. "UNICEF said the virus had spread quickly from the communities of Macenta, Gueckedou, and Kissidougou to the capital. The health ministry said 80 cases including 59 deaths had been reported, most of them in three southern prefectures near neighbouring Sierra Leone and Liberia." See: http://www.theguardian.com/world/2014/mar/23/guinea-ebola-outbreak-conakry
A French laboratory in Lyon confirmed it is Ebola.

"Ebola outbreaks have been restricted to Africa, with the exception of Reston ebolavirus. The International Committee on Taxonomy of Viruses currently recognizes four species of Ebola: Zaire virus (ZEBOV), Sudan ebolavirus (SEBOV), Reston ebolavirus (REBOV), and Cote d'Ivoire ebolavirus (CIEBOV)1. One additional species of type of Ebola is often recognized by the World Health Organization (WHO) and Centers for Disease Control and Prevention (CDC) as Bundibugyo ebolavirus or Ebola-Bundibugyo, following the outbreak in Uganda in 2007 (2)(3)(4)

Transmission between natural reservoirs and humans is rare, and outbreaks are often traceable to a single index case where an individual has handled the carcass of a gorilla, chimpanzee, or duiker (5). The virus then spreads person-to-person, especially within families, hospitals, and during some mortuary rituals where contact among individuals becomes more likely (6). Before outbreaks are confirmed in areas of weak surveillance on the local or regional levels, Ebola is often mistaken for malaria, typhoid fever, dysentery, influenza, or various bacterial infections which may be endemic to the region. Learning from failed responses, such as that to the 2000 Uganda outbreak, public health measures including the WHO's Global Outbreak and Response Network were instituted in areas at high risk. Field laboratories were established in order to confirm cases, instead of shipping samples to South Africa(7)." See: http://en.wikipedia.org/wiki/List_of_Ebola_outbreaks


Of course one of the more high profile ebola cases was the accidental infection of a Russian scientist at Vector in Novosibirsk who died in May of 2004. According to the New York Times, the scientist identified as Antonina Presnyakova was working on an Ebola vaccine. (http://www.cidrap.umn.edu/news-perspective/2004/05/russian-scientist-dies-ebola-after-lab-accident) There have been noted laboratory accidents involving Ebola and the need to develop a vaccine has long been persued. In 2011, an Abstract entitled: "Management of accidental exposure to Ebola virus in the biosafety level 4 laboratory, Hamburg, Germany was published by PubMed, see: http://www.ncbi.nlm.nih.gov/pubmed/21987751, the Abstract stated: "A needlestick injury occurred during an animal experiment in the biosafety level 4 laboratory in Hamburg, Germany, in March 2009. The syringe contained Zaire ebolavirus (ZEBOV) mixed with Freund's adjuvant. Neither an approved treatment nor a postexposure prophylaxis (PEP) exists for Ebola hemorrhagic fever. Following a risk benefit assessment, it was recommended the exposed person take an experimental vaccine that had shown PEP efficacy in ZEBOV-infected nonhuman primates (NHPs) (12). The vaccine, which had not been used previously in humans, was a live-attenuated recombinant vesicular stomatitis virus (recVSV) expressing the glycoprotein of ZEBOV. A single does of 5 x10(7) plaque-forming units was injected 48 hours after the accident. The vaccinee developed fever 12 hours later and recVSV viremia was detectable by polymerase chain reaction (PCR) for 2 days. Otherwise, the person remained healthy, and ZEBOV RNA, except for the glycoprotein gene expressed in the vaccine, was never detected in serum and peripheral blood mononuclear cells during the 3 week observation period. See: http://www.ncbi.nlm.nih.gov/pubmed/21987751 


Vaccine research and development to prevent and or treat post exposure has faced significant obstacles, with the overriding issue being one of investment.  Several research groups have developed experimental vaccines, including approaches based on DNA, recombinant adenovirus, virus-like particles and human parainfluenza virus 3. ( http://www.sciencedaily.com/releases/2013/01/130114161501.htm). In 2008, Crucell, a Dutch based bio-pharmaceutical firm received an NIAID/NIH contract to develop Ebola and Marburg vaccine candidates. Crucell notes: 

"Because of the high disease-related mortality rates and lack of any vaccine or therapy, the Ebola and Marburg viruses are on the US Centers for Disease Control and Prevention Category “A” list of bioterror agents, together with smallpox and anthrax. AdVac(R) technology is a vaccine technology developed by Crucell and is considered to play an important role in the fight against emerging and re-emerging infectious diseases, and in biodefense. The technology supports the practice of inserting genetic material from the disease-causing virus or parasite into a ‘vehicle’ called a vector, which then delivers the immunogenic material directly to the immune system. Most vectors are based on an adenovirus, such as the virus that causes the common cold. The AdVac(R) technology is specifically designed to manage the problem of pre-existing immunity in humans against the most commonly used recombinant vaccine vector, adenovirus serotype 5 (Ad5), without compromising large-scale production capabilities or the immunogenic properties of Ad5. AdVac(R) technology is based on adenoviruses that do not regularly occur in the human population, such as Ad35. In contrast to for instance Ad35 antibodies, antibodies to Ad5 are widespread among people of all ages and are known to lower the immune response to Ad5-based vaccines, thereby impairing the efficacy of these vaccines. All vaccine candidates based on AdVac(R) are produced using Crucell’s PER.C6(R) production technology."

Read more at http://www.redorbit.com/news/health/1576640/crucell_receives_niaidnih_contract_for_development_of_ebola_and_marburg/#A9h3lCWMfH50qVXL.99
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Jill Bellamy is an internationally recognized expert on biological warfare and defence. She has formerly advised NATO and for the past seventeen years has represented a number of bio-pharmaceutical and government clients working on procurement strategy between NATO MS and Washington DC. Her articles have appeared in the National Review, The Wall Street Journal, The Washington Post, The Sunday Times of London, Le Temps, Le Monde and the Jerusalem Post among other publications. She is a CBRN SME with the U.S. Department of Defence, Chemical, Biological, Radiological and Nuclear Defence Information Analysis Center and CEO of Warfare Technology Analytics, a private consultancy based in the Netherlands. She is an Associate Fellow with the Henry Jackson Society, UK.




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