Ebola Vaccines

Viral infections have always had and still have a huge impact on human health. If we mention a couple of examples—smallpox and human immunodeficiency virus (HIV)—the reader will identify HIV as representing a much greater health problem than smallpox. This is because smallpox—one of the most deadly and devastating diseases in the world— has been eradicated. When Europe was being ravaged by smallpox, the English physician Edward Jenner (1749-1823) noticed that women who milked cows and had lesions on their hands appeared to be protected against the disease. These lesions were produced by cowpox, a virus that proved to be an effective vaccine against human smallpox. As a result, the Latin word for a cow (vacca) has given us the modern term vaccine. Currently, we only have antiviral therapies for a small number of viruses, but fortunately we do have effective vaccines against quite a few, which has made it possible to control dreaded diseases such as polio and yellow fever.

The current epidemic in West Africa is the largest ever outbreak of the Ebola virus, generating more cases and causing more deaths than all the previous epidemics combined. This new situation reflects the fact that we face an epidemic of unknown magnitude and that previous outbreaks involved relatively few cases. With a total now exceeding 5,000 cases, the current outbreak has more than doubled the combined total of the approximately 2,000 cases of Ebola virus infection reported in all previous epidemics. While the number of those infected with this serious and alarming disease is cause for great concern, it is nonetheless relatively low compared to the numbers of those affected by malaria, HIV and tuberculosis.

The current lack of success in controlling the epidemic can be explained by several factors, including economic and structural issues, the level of development of the areas affected, community attitudes to the disease (both acceptance and resistance), lack of support, and the very nature of human beings. The problem is further aggravated by the lack of available treatments or vaccines to fight the Ebola virus.

While an effective treatment would be the tool of choice to combat the epidemic, it would obviously also be of great interest to have a vaccine against this deadly disease.

Why do we need an Ebola vaccine and who should be vaccinated?

Probably the most important candidates for vaccination at this time are the health personnel who are in contact or may come into contact with infected people in the African countries affected. We must remember that these countries often have a weak medical infrastructure and a limited number of doctors and other health professionals to deal with the task of caring for a large number of patients (not just those affected by Ebola but also patients with many other diseases). A significant number of medical professionals (over 200) working in the countries affected have already been infected, and over 100 have died. The consequences of these deaths are disastrous. Now there are even fewer qualified professionals to care for those newly-infected with Ebola and for patients with other infectious diseases. The shortage of medical personnel, together with the fact that people are frightened and may not go to a hospital when they are sick, can in turn lead to an increase in mortality from other infectious diseases, which can be substantial.

A vaccine could also be a useful tool in limiting the spread of the virus in the current epidemic. Vaccinating the population living close to areas with high concentrations of cases could help to contain the spread of the disease.

The other group of candidates for vaccination would be researchers working with the live virus. Obviously, work with the Ebola virus is only carried out in biosafety level 4 laboratories (the highest level) and it is regulated by extremely strict work protocols. However, human error and accidents are possible and it is very likely that this group could also benefit from an Ebola vaccine.

What vaccines have been investigated and what stage of development have they reached?

Ebola vaccine research is not new; it has been underway since the 1980s. Several vaccine candidates have been tested, including inactivated vaccines (based on “killed” virus), DNA vaccines (injection of plasmids that express the proteins of the target virus), virus-like particles (a “pseudovirus” which displays virus proteins that do not multiply in the body), and vector-based vaccines (in which other viruses are genetically modified to express and display Ebola virus proteins). Vectors that have been used include adenovirus, vaccinia virus, parainfluenza virus, and vesicular stomatitis virus. Greatly simplified, the concept is similar in all cases: elements that trigger an immune response against the virus proteins are introduced into our bodies. If we are then exposed to the Ebola virus, our bodies can block it because we are already equipped with the necessary antibodies and/or other immune mechanisms.

Of all of the vaccine candidates that have been developed and tested in animal models, two are of particular interest because they are in a more advanced phase of development and have achieved promising results: the vaccines based on adenovirus and the vaccine based on the vesicular stomatitis virus (VSV). These are being developed through joint efforts involving pharmaceutical companies (GlaxoSmithKline, Johnson & Johnson, and NewLinkGenetics) and public agencies (the US National Institute of Allergy and Infectious Diseases and the Public Health Agency of Canada). At least from an outside perspective, the intervention of public-private partnerships is not surprising since the Ebola virus does not generate a sufficient number of cases each year to warrant the interest of a private company and very few public agencies have the infrastructure needed to develop a commercial vaccine.

The drawback of adenovirus-based vaccines is that a large percentage of the population have already been exposed to these viruses (they are frequent causes of respiratory and gastrointestinal infections). A person who has previously had an adenovirus infection probably has antibodies that will block any Ebola vaccine based on these viruses. This limitation has, in theory at least, been overcome through the use of chimpanzee adenovirus to which humans should not have developed antibodies. Phase I trials are already underway to assess the safety of the vaccine based on chimpanzee adenovirus and to ascertain whether it produces an immune response in healthy volunteers. It is probably the most advanced candidate vaccine. Recently reported evidence shows that it protects monkeys for at least 10 months, although such protection required doses of two different vaccines.

The VSV-based vaccine appears to be ready for Phase I trials, which have been approved by the Food and Drug Administration (FDA), the agency that regulates drugs and vaccines in the USA. The theoretical disadvantage of a vaccine based on an attenuated live virus is that it could potentially cause infection in humans, although VSV infections are rare and usually mild. It has, however, been tested extensively with excellent results under different conditions in monkey animal models. Moreover, it has been shown to offer post-exposure protection, that is, it appears to prevent disease caused by the Ebola virus even when the vaccine is administered very soon after the organism is infected. The vaccine has even been given to a researcher who had a laboratory accident with a syringe containing the Ebola virus. The researcher did not develop the disease; however, the evidence is insufficient to demonstrate the effectiveness of the vaccine in that case because it is impossible to know whether or not he would have developed the disease if he had not received the vaccine.

In conclusion, it is likely that the alarming and unusual Ebola epidemic in West Africa will help to speed up the development of treatments and vaccines for this disease and having these tools to combat the virus is desirable and necessary. But we should not forget that, ultimately, the epidemic will most likely be brought to an end by the daily efforts of health workers in the area who implement effective containment and isolation measures.

Mikel Martínez is a microbiologist at the Hospital Clínic i Provincial de Barcelona, associate medical professor at the University of Barcelona and a researcher at the Barcelona Institute for Global Health.

Article previously published in El Mundo (01/10/2014)