A World Free from Ebola: the Vaccines

It has been widely reported in the press that a new vaccine trial has entered the second round of testing at Oxford University in the UK. Now that reserves of the once-hailed ZMAPP vaccine have run out, the focus of attention has shifted to the major pharmaceutical companies that are working hard to develop a vaccine to stem the tide of Ebola.

I thought that it would be worthwhile to investigate how these drugs are brought to market, and what their impact would be on the situation today, in the coming months, and for the world in the future. Whilst many understand the benefits of a vaccine, it is an alarmingly complex and expensive process for these private companies to embark on, and one that we should all understand our role in facilitating.

How do we combat Ebola currently?
It is well documented that the survival rate of Ebola in Western countries is significantly higher than that in West Africa. The quality of healthcare, an immediate interest in controlling the disease, and the provision of newly developed drugs have all helped to achieve this. Key to achieving a higher survival rate in West Africa has been an early identification of the virus, whilst the provision of fluids and antibiotics dramatically increase the chance of survival. Sufferers of Ebola can lose up to 10 litres of liquids per day through bleeding, vomiting, and diarrhoea, so by replenishing these lost fluids we can help to stop the collapse of vital organs and a further decline of the immune system.

With the healthcare facilities receiving the greatest attention from the world media, it is easy to forget that a portion of the response effort and funding is going in to developing technologies and medicines. In this post we will cover many of the current developments and experimental landscape in the fight against Ebola.

In terms of technology, there is a 15-minute Ebola test being developed by the French Atomic Energy Commission (CEA) went on trial in Guinea in October.[1] The test kit is similar to a pregnancy test and requires only a drop or two of blood or urine to work; we are still awaiting the results of the trial. Simultaneously, a team out of MIT is developing nanotechnology to be able to print active molecules on to paper, to which the Ebola virus will stick. [2] The objective is to have these pieces of paper, similar to a litmus test strip, stored in every First Aid Kit in the region. What is notable and progressive about both of these technologies is that they are designed to be near-immediate low-tech solutions administered at the point of care. This would enable medical staff to isolate and treat the patient whilst avoiding a risky visit to an Ebola treatment centre and potentially further contagion.

Pertinent to this article was the announcement that the World Health Organisation has agreed that it is ethical to use unproven drugs in the current epidemic.[3] This has paved the route for medical trials and experimental drug administration. Whilst in theory this can be lifesaving, the administration of these drugs in a non-laboratory testing environment leads to it’s own issues. In the cases where these innovative drugs have been used, the recipients have been receiving a combination of care and therefore it is difficult to identify which is the active agent in saving them from the virus. For example, Will Pooley, the first NHS health worker to have contracted the virus, was administered the drug ZMAPP along with 7 other Ebola sufferers. Pooley survived, unfortunately two of the seven didn’t. This highlights that the drugs developed are, firstly, not a cure, and secondly, have not achieved the consistency to be called a treatment. In many cases, it is considered that the strength of the patient’s own immune system has, in fact, been a major contributory factor.

What are the options?
Aside from developing drugs, there is another kind of experimental treatment that has gained traction over the last few weeks: convalescent therapies. Convalescent therapy is the process of injecting blood from recovered patients into sick patients, and has had promising results. The New York Times writes that WHO officials are prioritising blood and plasma therapies for treatment, but there are major questions about its safety and efficacy in countries with inefficient health systems and a shortage of medical staff.[4]

As these convalescent therapies are beginning to be instrumented, although it is not clear how widely or effectively, the pharmaceutical companies are drawing on a mix of historical research and international funding in the race to develop an Ebola vaccine. There are three drugs currently on trial that look most likely for a near-future breakthrough.

ZMapp is, for now, out of the picture; there are no more stocks anywhere in the world. The Food and Drug Administration (FDA) in the United States has promised the company more than $42m (£27.6m) to speed up production and trials, but the drug consists of three monoclonal antibodies that have to be grown in the leaves of genetically modified tobacco plants, which takes months. It is also very expensive, which means that mass production for Africa is unlikely.[5]

The centre for Infectious Disease Research & Policy reports that the vaccine currently being trialled at Oxford University is being developed by Johnson & Johnson’s Janssen Pharmaceutical Companies. Another drug is being developed by the National Institutes of Health (NIH) and GlaxoSmithKline (GSK) named ChAD3, and another developed by Canadian researchers and licensed by NewLink Genetics and Merck named VSV-EBOV – these latter two are on phase 1 trials as well.

The preclinical studies of the Johnson & Johnson’s vaccine at the National Institutes of Health (NIH) found that, when given 2 months apart, completely protected nonhuman primates against death from the Kikwit Zaire strain of the virus.[6]

According to a statement on their website, the GSK drug ChAd3 uses a type of chimpanzee cold virus, known as chimpanzee adenovirus type 3, as a carrier to deliver genetic material from two strains of the Ebola virus – the Sudan strain and the Zaire strain. It goes on to say that first results show that the vaccine was well-tolerated and produced an immunological response in each of the 20 healthy adult volunteers.[7]

The VSV-EBOV vaccine is made from another virus, V.S.V., for vesicular stomatitis virus that has been used successfully in making other vaccines. The researchers altered V.S.V. by removing one of its genes — rendering the virus harmless — and inserting a gene from Ebola. The transplanted gene forces V.S.V. to sprout Ebola proteins on its surface.[8]

All of the above drugs have had some success in vaccinating primates from the Ebola virus, and all have very different methods of application, so it will be interesting to see which wins the race to market. It is, indeed, the market to which they are heading: we all know that producing drugs is a business, naturally based on profit rather than humanitarian concern, but it is interesting to read about the costs and funding. The development process highlights the central role of NGOs and governments alongside the big pharmaceutical companies.

What are the costs and benefits of developing drugs?
Mahga Kamal-Yanni, Oxfam’s senior health-policy advisor says that “large companies will not invest in research and development for rare and neglected diseases, due to the limited scope for profit. It is neither ethical nor sustainable to leave decisions and financing for research and development to be dictated by the commercial interests of pharmaceutical companies. They will continue producing the medicines that can make the highest profits rather than the therapies that are desperately needed for public health.”[9]

In a New York Times article, Dr. Thomas Geisbert, a member of the team that initially undertook the research on the VSV-EBOV drug 12 years ago, explains the cost-need ratio of the drug industry, and outlines why it has taken so long for his research to be utilised. In this excerpt, he begins talking about the point where he left the drug, after the first round of small trials had been undertaken.

“To that point, the research may have cost a few million dollars, but tests in humans and scaling up production can cost hundreds of millions, and bringing a new vaccine all the way to market typically costs $1 billion to $1.5 billion, Dr. Crowe said. “Who’s going to pay for that?” he asked. “People invest in order to get money back.”[10]

The answer to that question is resolved by the appearance of epidemics such as Ebola. The landscape of research and development funding in a time of crisis makes the pharmaceutical companies more inclined to embark on these ventures. Take, for example, the GSk drug ChAd3. Despite the testing process becomes significantly de-regulated – as pointed out by the WHO announcement on the ethics of administering untested drugs – the big pharmaceutical companies are provided with funds to undertake the development. A high-level emergency meeting between WHO officials and other key players in October insisted that “funding issues should not be allowed to dictate the vaccine agenda.” The minutes concluded that “The funds will be found.”[11] It was announced that for the latest round of testing in Oxford, not to be confused with the Johnson & Johnson testing set underway this week, GSK received a £2.8 million grant from an international consortium consisting of the Wellcome Trust, the Medical Research Council (MRC) and the UK Department for International Development (DFID). The GSK website explains that the consortium’s funding will also enable them to begin manufacturing up to around 10,000 additional doses of the vaccine at the same time as the initial clinical trials, so that if the trials are successful stocks could then be made available immediately by GSK to the WHO to create an emergency immunisation programme for high-risk communities.[12]

Whether you agree with the decision to provide financial and resource-incentive to big pharmaceutical companies, there is little other choice. When the world is gripped by an outbreak on this scale, it is for the international community to financially incentivise those private companies that have the capacity and knowledge to do this.

If we create an effective drug, what is the likely effect on the current outbreak?
Firstly, it is worth noting that vaccines are generally designed to prevent diseases rather than to cure them. However, as may have been in the case of ZMAPP, there is the hope that these vaccines will also have a curative element to them. Only testing and time will answer this question.

GSK writes on their website that, if the phase 1 trials are successful, they can begin the next phases of the clinical trial programme which will involve the vaccination of thousands of frontline healthcare workers in the three affected countries – Sierra Leone, Guinea and Liberia. If the vaccine candidate is able to protect these healthcare workers, it could significantly contribute to efforts to bring this epidemic under control.[13]

A widespread vaccination of medical staff and general public throughout West Africa would paralyse Ebola in it’s tracks. It would represent a cataclysmic blow to the spread of the virus, and would effectively render the crisis over. However, this would not be the end of the vaccine. If this crisis has showed us anything, it is that an early and coordinated response effort is key to controlling the virus and it’s spread.

In 2010 the Sierra Leonean statehouse introduced the Free Health Care Policy which aimed particularly to provide care and protection to mothers and children under 5. As part of this programme, the administration of a a Pentavalent vaccine which is five individual vaccines conjugated in one actively protecta infant children from 5 potentially deadly diseases: Haemophilus Influenza type B (the bacteria that causes meningitis, pneumonia and otitis), Whooping Cough (or Pertussis), Tetanus, Hepatitis B and Diphtheria. In the wake of the Free Health Care Policy, immunisation has been taken up well with 75% of relevant age-groups receiving the immunisation, according to a WHO report. Whether the Ebola vaccine is one that could be added to this mixture, or administered alongside it remains to be seen, and will depend largely on cost and access. What is certain is that the development of a vaccine will be useful in beating the current outbreak and any future outbreaks of this vicious virus.

It is unfortunate that the mechanisms of pharmaceutical development dictate that it takes an epidemic of this proportion to engage the research and development required. However, we should be thankful that the systems and funding are in place to do such development. It will be a long and lasting development that will continue to have positive implications for the future. It will be down the governments of not only West Africa, but all of those countries in Africa where bush meat remains a part of daily life, to ensure that national stocks are maintained to avoid any future Ebola crisis.

Vaccines are in development, and it is surely only a matter of time until they are available for widespread use. Until that point, we must remain on our course of localised isolation, care, and treatment of those pooor souls who contracted Ebola

We’re fighting for a life #AfterEbola, please help.

[1] http://www.meddeviceonline.com/doc/quick-ebola-diagnostic-device-developed-by-french-researchers-0001
[2] http://www.meddeviceonline.com/doc/mit-researchers-develop-rapid-paper-diagnostic-for-ebola-0001
[3] http://www.nytimes.com/interactive/2014/10/23/world/africa/ebola-drugs.html
[4] http://www.nytimes.com/interactive/2014/10/23/world/africa/ebola-drugs.html
[5] http://www.theguardian.com/world/2015/jan/05/ebola-zmapp-stocks-run-out-doctors-turn-alternative-treatments
[6] http://www.cidrap.umn.edu/news-perspective/2015/01/uk-researchers-launch-human-trial-third-ebola-vaccine
[7] http://www.gsk.com/en-gb/media/press-releases/2014/gsk-statement-on-first-phase-1-trial-results-of-a-candidate-ebola-vaccine/
[8] http://www.nytimes.com/2014/10/24/health/without-lucrative-market-potential-ebola-vaccine-was-shelved-for-years.html?_r=0

[9] http://www.independent.co.uk/life-style/health-and-families/health-news/ebola-virus-what-price-for-a-miracle-cure-9785917.html

[10] http://www.nytimes.com/2014/10/24/health/without-lucrative-market-potential-ebola-vaccine-was-shelved-for-years.html?_r=0

[11] http://www.who.int/mediacentre/news/ebola/23-october-2014/en/

[12] http://www.gsk.com/en-gb/media/press-releases/2014/ebola-vaccine-trials-fast-tracked-by-international-consortium/

[13] http://www.gsk.com/en-gb/our-stories/health-for-all/our-contribution-to-the-fight-against-ebola/

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