NIH Ebola Update: Working Toward Treatments and Vaccines
Posted on by Drs. Anthony S. Fauci and Francis S. Collins
Credit: National Institutes of Health
Updated Oct. 22, 2014: The National Institutes of Health (NIH) today announced the start of human clinical trials of a second Ebola vaccine candidate at the NIH Clinical Center in Bethesda, MD. In this early phase trial, researchers from NIH’s National Institute of Allergy and Infectious Diseases (NIAID) are evaluating the vaccine, called VSV-ZEBOV, for its safety and ability to generate an immune response in healthy adults who receive two intramuscular doses, called a prime-boost strategy.
The Walter Reed Army Institute of Research is simultaneously testing the vaccine candidate as a single dose at its Clinical Trials Center in Silver Spring, MD. VSV-ZEBOV, which was developed by researchers at the Public Health Agency of Canada’s National Microbiology Laboratory, has been licensed to NewLink Genetics Corp. through its wholly owned subsidiary BioProtection Systems, both based in Ames, Iowa.
Early human testing of another Ebola vaccine candidate, co-developed by NIAID and GlaxoSmithKline, began in early September at the NIH Clinical Center. Initial data on that vaccine’s safety and ability to generate an immune response are expected by the end of 2014.
We are all alarmed by the scope and scale of the human tragedy occurring in West African nations affected by the Ebola virus disease epidemic. While the cornerstones of the Ebola response remain prompt diagnosis and isolation of patients, tracing of contacts, and proper protective equipment for healthcare workers, the National Institutes of Health (NIH), led by its National Institute of Allergy and Infectious Diseases (NIAID), is spearheading efforts to develop treatments and a vaccine for Ebola as quickly as possible.
For example, NIAID has supported and collaborated with Mapp Biopharmaceutical, Inc., San Diego, in its development of the product known as ZMapp, which has been administered experimentally to several Ebola-infected patients. While it is not possible at this time to determine whether ZMapp benefited these patients, NIAID is supporting a broader effort to advance development and clinical testing of ZMapp to determine if it is safe and effective. In addition, the U.S. Biodefense Advanced Research and Development Agency (BARDA) has announced plans to optimize and accelerate the manufacturing of ZMapp, which is in limited supply, to enable clinical safety testing to proceed as soon as possible.
NIAID is also supporting the development of other potential treatments. Among them is BCX4430, a drug that BioCryst Pharmaceuticals, Research Triangle Park, NC, plans to enter into a Phase 1 human clinical trial by early 2015. Another potential drug, brincidofovir, developed by Chimerix of Durham, N.C., has been evaluated in more than 1,000 patients for two non-Ebola viruses (cytomegalovirus, adenovirus). Brincidofovir has shown some ability to suppress Ebola viruses in cell cultures, and was recently administered to several patients with Ebola virus disease. Again, while it is impossible to determine on the basis of a few patients whether a drug is effective against Ebola, brincidofovir appears to be safe in humans. Broader evaluation of the drug will likely take place in the coming months.
In addition, the HIV drug, lamivudine, has also been used in some Ebola patients in Liberia, under the supervision of a Liberian physician. Cell culture testing of the drug is being conducted in the United States, and if promising, clinical trials could be performed.
A safe and effective Ebola vaccine could be a critically important tool to help prevent Ebola virus infection and help contain the present and future outbreaks. Several Ebola vaccine candidates are undergoing Phase 1 human clinical testing this fall after proving effective in animals. One of these is a vaccine candidate developed by NIAID and GlaxoSmithKline, London; this product entered a small Phase 1 study at the NIH Clinical Center in Bethesda, MD, last month, and the study is now expanding to additional sites.
Additionally, NIH will collaborate with the Department of Defense and NewLink Genetics Corp., Ames, IA, on Phase 1 human safety studies of another investigational Ebola vaccine candidate, which was developed by and licensed from the Public Health Agency of Canada. Other vaccine candidates are in earlier stages of development in animal models. Knowledge gained through all of these studies will further the goal of deploying a safe and effective vaccine that will prevent this deadly disease.
During this extremely serious outbreak of Ebola virus disease in West Africa, we must balance the urgent desire to deploy experimental countermeasures with the need to ensure safety and determine the efficacy of the products. We would not want to introduce products, particularly preventive measures for healthy, uninfected individuals, if they are ineffective or even harmful.
Randomized, controlled clinical trials remain the “gold standard” for the evaluation of candidate drugs and vaccines because they represent the most efficient way to prove efficacy and safety. This is an imperative for any intervention delivered to healthy individuals. As we proceed through clinical testing, NIH will continue to work with our partners at BARDA, the Food and Drug Administration (FDA), and elsewhere to accelerate efforts to develop and provide access to Ebola vaccines and treatments in a manner that is both scientifically and ethically sound.
Note: Anthony S. Fauci, M.D., is Director of the National Institute of Allergy and Infectious Diseases (NIAID), NIH
Links:
Understanding Ebola and Marburg hemorrhagic fevers (NIAID)
Ebola/Marburg Research (NIAID)
Ebola–underscoring the global disparities in health care resources.
Fauci AS. N Engl J Med. 2014 Sep 18;371(12):1084-6.
Ebola Virus Disease (CDC)
CDC: Stopping the Ebola Outbreak
NIH support: National Institute of Allergy and Infectious Diseases
Tekmira – no mention of TKM-E even though Dept of Defense has a working contract with them and TKM was successfuly used to cure Dr. Sacra at Nebraska Med Center
Dear Doug and others,
Thank you for your comments. This blog post, as Drs. Fauci and Collins note in their first paragraph, is focused on National Institutes of Health (NIH)-supported research aimed at developing treatments and a vaccine for Ebola virus disease. As you point out, a number of others in the public and private sectors are also working on Ebola therapeutics and vaccines.
Transfer known Ebola patients to one of three or four specialty hospitals in America. These hospitals are better trained to combat the virus.
Dr. Fauci,
I am so glad that we have you.
Couple of thoughts/questions on Ebola patient care:
>the patient with diarrhea- –
)1, Question of fluid regimen in the treatment West African treatment centers with no lab or resources for invasive fluid administration?
)2. Please note that symptoms of chlorine toxicity include abdominal pain, bloody diarrhea, and respiratory distress—plus release of chloroform.
)3. Small doses of oral Paragoric, denatured
tincture of opium, is very effective at putting
the diarrhea patient and their bowel at rest.
Good luck and thank you for being there doctor Fauci.
Wayne
What happened to the NIH Ebola vaccine using DNA which had successful Phase I results in 2006? …
you don’t sound too informed.. You completely left of Tekmiras vaccine TKM-Ebola, which is ahead of all of these drugs in development and has the best manufacturing capability if there was an outbreak.
No mention of Sarepta’s Ebola druga as well, which is in stock, but unused since sequester and has partially completed human safety testing. Seems like we should be trying all available drugs.
What about DepoVax developed by Immunovaccine!!???
The lethal effect of ebola infection is extremely high innate inflammation, leaving no room and time for adaptive immunity to kick in. Thus, the correct treatment strategy of anti-ebola should be anti-inflammation. Once inflammation is under control adaptive immunity will take over and heal the host. Please consider this seriously or tell us why it is not a right thinking.
See Sarepta for the Ebola treatment ,it works
With Nina Pham transferring to NIH, I suspect that antiviral treatments may have failed to control the worsening of her conditions. There are plenty reasons why these approaches won’t work. I hope that I am wrong, but if I am right, it will be a serious challenge to continued antiviral therapy Dr. Fauci can offer at NIH. As I have pointed out yesterday, the key is not antiviral at this stage, but anti-inflammation. The host’s adaptive immune system is capable of clearing the virus when not under severe innate inflammation. Suppress the inflammation with steroids or chemo drugs to allow adaptive immunity to kick in. …
hi my name is Joey I’m nine years old and this is why I think the flu shot will work for Ebola .I think the flu shot would work for Ebola because it works like a flu even though it is not the same bug so to me it’s just a really bad flu and if you increase the power of a flu shot it might just cure Ebola.
NIAID is also supporting the development of other potential treatments. Please consider this seriously or tell us why it is not a right thinking.
Per the original comment to Doug re: TKMR and then another question about SRPT. Both have a treatment, one which has been tried in patients and one which has gone through safety testing. They are not part of the NIH funded research, and therefore there is no vested interest in them; therefore no one is advocating for them. They are public companies and are not going to pony up the huge investments required. So the right answer might very well be hidden in plain sight, and no mechanism to get them into the process.
Dear Drs. Fauci and Collins,
A full 2 weeks before this post I searched the NIH’s own Pubmed (anyone can do this) and found a study from last year that DTRA funded to screen FDA approved drugs (http://www.ncbi.nlm.nih.gov/pubmed/23577127). Several drugs (Amodiaquine, Chloroquine, etc.) were found active and with promising data in mouse models. A doctor in Haiti then alerted me to another paper with additional compounds (http://www.ncbi.nlm.nih.gov/pubmed/23785035). It appears there are no shortage of FDA-approved drugs that have activity in vitro and in vivo in mouse etc.. there is even a common pharmacophore which I put in the public domain … [Ekins, Sean (2014): A pharmacophore of ebola active compounds. figshare.
http://dx.doi.org/10.6084/m9.figshare.1190787%5D
It would not take much for any of these drugs to be explored further. I am amazed that all the discussion is on a vaccine /biologics and yet there has been considerable efforts to fund screens of small molecule drugs and they have been largely ignored. I am also saddened by the lack of big pharma response …
We have known about the disease for 40 years and yet we did not have a plan for when it went beyond one village in Africa? That is very surprising to me as a scientist. There are many questions that someone should answer, like why was the funding for small molecule screening and exploration of the hits/leads stopped? Why was there no exhaustive effort to screen every FDA-approved drug? Why are the existing drugs already on the shelf in Africa not being used? Why is nobody looking at those that are not getting Ebola, is it because they are already taking a medicine that is protecting them?
Food for thought.
it is hard to contain something that we don’t understand how to stop just yet.
let’s continue to pray and hope to find a cure soon.
I know it’s a terrible disease because of the pictures i’ve seen.
I think the flu shot would work for Ebola because it works like a flu even though it is not the same bug so to me it’s just a really bad flu and if you increase the power of a flu shot it might just cure Ebola.Thanks for share.
I’m wondering if there are any updates on tests related to Lamivudine as a possible treatment for Ebola, either by NIH, or in the field by Dr. Logan in Liberian, or any other doctors in affected countries.
2 HIV drugs were tested in vitro and were inactive compared with the SERM Toremifene a video from NIAID discussed this last week https://www.youtube.com/watch?v=inIL5Zf97gY&feature=youtu.be but Lamivudine was not mentioned, neither were the antimalarials.
I watched the video. 3TC, also known as Lamivudine, is considered ineffective. Now I’m just curious if Dr. Logan has continued using it, and if so, what further results he has obtained.
I watched the video a second time, and realized that the graph showing that Lamivudine (3TC) wasn’t effective was dated 10-3-14. This was well before this current blog post was put up. In fact, I think this might be what Dr. Fauci was referring to in the initial tests of Lamivudine. So is Lamivudine going to be given further tests or not?
Thanks for your comment, Julian. As Drs. Fauci and Collins noted in their blog post: “In addition, the HIV drug, lamivudine, has also been used in some Ebola patients in Liberia, under the supervision of a Liberian physician. Cell culture testing of the drug is being conducted in the United States, and if promising, clinical trials could be performed.”
Hi Moderator,
Thank you for your patience. Just a few more questions and I promise not to bother you anymore. First, when can we expect to hear the results of those tests on Lamivudine? Second, is the NIH interested in knowing if Dr. Logan has continued administering Lamivudine to Ebola patients? Third, if so, is the NIH also interested in knowing whether he has continued to have the same sort of success he seemed to have with the first 13 out of 15 patients? Or (and this is my final question) would that information be considered entirely irrelevant to determining whether or not Lamivudine is an effective therpeutic treatment for Ebola? Thank you for your patience.