Ebola Virus Vaccines

I can only offer a plausible WAG.

I suspect that part of the problem with every strain of Ebola is that the human body does not produce antibodies in response to an infection. Infecting us with a non-pathogenic strain of Ebola therefore just adds to our biome another benign hitchhiker.

I´m a simple neurosurgeon, and don´t have a reply to your question. As far as I know Ebola Reston is a virus that infects certain monkeys and pigs. Although people working with these monkeys may have positive blood tests (meaning they have been infected), they did not develop the disease so far. As the African Ebola virus has a different chemical and /or immunologic pattern, vaccinating people with Ebola Reston may probably make no sense (I guess). On the other hand, despite this may shock you: the Pharma industry has no interest in investing zillions for developing a specific vaccine for small (and poor) markets.

r&ddoc, there have been a few humans over the years who have been infected (and therefore developed antibodies) but did not get sick. Recently pigs have been found infected with it and since they are immunologically similar to both Humans and Birds and can be infected with viruses from both, there is some concern that it may swap plasmids with other viruses and become much more dangerous. From what I've been able to learn through Google the vaccine work has focused on DNA vaccines since they are inherently safer (and I can see safety being a major concern here of course) and they work in Guinea Pig and mouse models but they don't appear to work in primate models for some heretofore unknown (or possibly unpublished) reason. But since people have been infected with Reston and developed antibodies but did not get ill, It would seem to me that you would have at least a starting point for a live virus vaccine. To make an effective one it might require grafting genes for proteins that appear on the viral surface from the other strains and that might make it virulent so of course that is a safety concern, but it would seem to me that using natural outbreaks to test the efficacy on those who may have been exposed but are still quarantined and had not developed symptoms yet would seem ethical given the mortality rates and the lack of an effective treatment protocol otherwise. Thoughts?

as to whether the Pharma industry is interested in developing such a vaccine, I'm sure Ft Detrick has been working on it, and other BSL4 labs, including Baylor here in Galveston are as well. and if the government were to wave enough money at them and give them immunity from lawsuits arising from it, they would be more than happy to toss their hat in the ring. After all, it is one of the viruses that scares the living crap out of the Biowarfare people. They are highly motivated to find a way to protect our soldiers from such an attack.

..."it is one of the viruses that scares the living crap out of the biowarfare people"... how do you know they already have the vaccine and keep it secret as a countermeasure?

I don't and actually suspect as much, which may explain why there isn't a whole lot about it I can find on Google...

The Reston ebolavirus is being studied, however in test using it as a vaccine against ebola, it was only 50% effective in monkeys....The effects are only known of the Reston in adult healthy males where no ill effects are witnessed, that might not be the case across the board...Ebola outbreaks are rare, extremely rare, less than 1000 deaths in the last 10 years, and I think all in Africa....We lose 20 to 30 thousand every year here in the US, from the flu....

it wouldn't work in primate models because reston has a 100% mortality rate in primates, so testing in primates wouldn't work. which means testing either in some other animal model which is pretty hit and miss, or humans. and human testing is fraught with ethical issues.

"Following the investigation in Indonesia, an experiment was conducted in the level-4 lab at the CDC campus in DeKalb County, Georgia with thirty-two monkeys: sixteen Green monkeys(Cercopithecus aethiops) and sixteen Crab-eating Macaques. Half of the sixteen Green monkeys and Crab-eating Macaques were infected with Reston virus and the other half with Ebola virus. Ebola virus infection was lethal to nearly all monkeys. However, most of the monkeys infected with Reston virus recovered in a month. The surviving monkeys were kept for two years to detect any trace of the virus - none was found. However, the monkeys continued to possess a high level of antigen.^[5]

Post-Reston[edit]

Following the test at the CDC campus in DeKalb County, two of the monkeys who had survived Reston virus infection were infected with a very large dose of the Ebola virus in an effort to produce an Ebola vaccine. One of the two monkeys remained resistant; the second died.^[5]"

^{http://en.wikipedia.org/wiki/Reston_virus}

hmm, news to me. I had read Reston had 100% mortality in monkeys. a 50% efficacy (albeit in a very small sample) would seem to indicate that there might be some value in infecting people exposed to ebola but not symptomatic yet with Reston as a prophylactic, or perhaps Gamma Gobulin shots with antigens to Reston and or ebola. It certainly would seem to not be harmful to try it at least.

The Reston ebolavirus has only been observed to be non-symptomatic in healthy human males....there is no proof that the results would be the same under any other circumstances....However imo testing those infected with ebola virus, and other related viral infections, with antigen based treatment might be acceptable on a case by case basis....

Here is a paper on methods being used now....

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1656552/

Fatal components have been identified in the Sudan species of Ebola...

http://www.ncbi.nlm.nih.gov/pubmed/17940968

Marburg and Ebola are both filoviruses.

Here is a link to some info on a small molecule broad spectrum vaccine that may end up being effective for both of the known human filovirus pathogens.

It looks like they are getting close.

http://www.theglobaldispatch.com/biocrysts-bcx4430-completely-protected-non-human-primate-from-marburg-48-hours-post-infection-45638/

http://www.nature.com/nature/journal/vaop/ncurrent/full/nature13027.html

http://en.wikipedia.org/wiki/NPC1

"Niemann-Pick C1 (NPC1) appears to be essential for Ebola infection. Two independent studies reported in the same issue of Nature (journal) showed that Ebola virus cell entry and replication requires the cholesterol transporter protein NPC1.[7][8] When cells from Niemann Pick Type C1 patients were exposed to Ebola virus in the laboratory, the cells survived and appeared immune to the virus, further indicating that Ebola relies on NPC1 to enter cells. This might imply that genetic mutations in the NPC1 gene in humans could make some people resistant to one of the deadliest known viruses affecting humans. The same studies described similar results with Ebola's cousin in the filovirus group, Marburg virus, showing that it too needs NPC1 to enter cells.[7][8] Furthermore, NPC1 was shown to be critical to filovirus entry because it mediates infection by binding directly to the viral envelope glycoprotein.[8] A later study confirmed the findings that NPC1 is a critical filovirus receptor that mediates infection by binding directly to the viral envelope glycoprotein and that the second lysosomal domain of NPC1 mediates this binding.[9]

In one of the original studies, a

small molecule was shown to inhibits Ebola virus infection by preventing the virus glycoprotein from binding to NPC1.[8][10] In the other study, mice that were heterozygous for NPC1 were shown to be protected from lethal challenge with mouse adapted Ebola virus.[7] Together, these studies suggest NPC1 may be potential therapeutic target for an Ebola anti-viral drug."

Excellent! the cell entry mechanism is key to treating infections after they have occurred. This is an important tool in the arsenal.

The idea of this treatment approach scares the hell out of me. If one just blocks the virus entry into the cell, then this treatment might turn a dieing patient into an immune carrier to spread it. Now that's a bio-weapon.

They would obviously have to be kept in isolation/quarantine until the infection passes. and anyone treating them would probably want to take the antiviral as a prophylactic as well. And get vaccinated if such a vaccine ever comes to fruition.

I´d rather ask a Infectologist!

Well, apparently the NIH has taken a more traditional route to a vaccine and found one that appears to be 100% effective in all primates tested so far. It is a modified Rabies live attenuated virus vaccine ( vaccines come full circle don't they? Rabies was one of the first ones Pasteur invented.) that expresses the Ebola Glycoproteins along with the Rabies ones, imparting 100% protection to both.

http://www.niaid.nih.gov/topics/ebolamarburg/Pages/rabiesVaccEbola.aspx