Understanding Ebola Vaccine Development

editorialWhat are the strategies scientists are using to develop vaccines to prevent Ebola?

By Mary Rushton

Last year an unprecedented outbreak of the highly lethal Ebola virus occurred in the West African countries of Guinea, Liberia, Nigeria, and Sierra Leone. This epidemic, which started in 2013, led to over 28,000 infections and has killed more than 11,000 people, making it the largest outbreak of Ebola ever. The number of new cases of Ebola infection declined dramatically since the height of the outbreak, with Liberia recently being declared Ebola-free. But the World Health Organization (WHO) continues to receive reports of new infections and fatalities in Guinea and Sierra Leone.

The most recent Ebola epidemic created a humanitarian crisis as it spread through highly populated corridors of these West African countries. The urgency of responding to the outbreak spurred public health officials, research institutions, and pharmaceutical companies to rapidly accelerate the development and testing of new drugs to treat and vaccines to prevent Ebola infection—none of which currently exist.

Now these efforts are bearing fruit. The first efficacy trial of an Ebola vaccine tested in 4,000 high-risk volunteers from Guinea who had recently been in close contact with Ebola-infected individuals shows a single dose of one vaccine candidate was safe and highly effective—in some cases 100% effective—in preventing Ebola infection.

The culprit

Ebola is a type of virus called a filovirus and is named after the river where it was discovered in 1976 in the central African country of Zaire, now the Democratic Republic of the Congo. Since then, 19 major and 14 minor Ebola outbreaks have occurred, primarily in Africa, and four additional species of the virus have been identified. Ebola has a wormlike structure that can infect and quickly overwhelm nearly every cell and organ in the human body. As a result, it is highly fatal. Of the 318 people diagnosed with Ebola during the first outbreak, 288 died—a case fatality rate of 88%. The virus is transmitted through direct contact with infected blood or bodily fluids.

Circle of protection

The first efficacy trial of an Ebola vaccine candidate provided results earlier this year. The candidate, known as rVSV-ZEBOV, was first developed by the Public Health Agency of Canada and is now manufactured by the pharmaceutical company Merck. The VSV in the candidate’s name stands for vesicular stomatitis virus. This virus, which primarily infects cattle, is disabled and used as what researchers call a viral vector to shuttle a gene from the Ebola virus into the body so that the immune system can create an immune response against it, without an actual Ebola infection occurring.

Scientists are using various viral vectors in HIV vaccine candidates as well, including VSV. Viral vectors are a promising strategy for pathogens like Ebola or HIV, for which a killed or weakened version of the pathogen is not feasible to use in a vaccine.

The efficacy trial of rVSV-ZEBOV in Guinea utilized a strategy called ring vaccination. Ring vaccinatHIV Orange xsection is so-named because the close contacts of an infected individual are immunized to create a ring of protection that can control the spread of the virus. Ring vaccination was used to contain the spread of smallpox in developing countries during a highly successful eradication campaign in the 1970s, but it is an unusual approach for testing the efficacy of a vaccine candidate.

In the Guinea trial, some rings of susceptible individuals were vaccinated immediately after the newly Ebola-infected person was identified, while other rings were vaccinated three weeks later, when the period of Ebola infectiousness was ending. This strategy allowed researchers to compare the efficacy between these different rings. It also enabled researchers to forego use of a placebo group.

The interim data published in July showed that none of the individuals in the immediately vaccinated rings contracted Ebola, while in the delayed rings, 16 Ebola infections were reported.

The WHO, with the approval of the Guinea government, plans to continue the trial to gather more conclusive evidence of how well the vaccine candidate induces herd immunity—when a high enough percentage of people are immunized that the chain of infection for contagious diseases is broken and the spread of disease within the community is contained (see VAX March 2015 Primer on Understanding Community Immunity).

Other vaccine candidates

Other Ebola vaccines are also in clinical development. Scientists from the US National Institute of Allergy and Infectious Diseases’ Vaccine Research Center and pharmaceutical company GlaxoSmithKline (GSK) recently conducted a Phase II clinical trial in Liberia comparing another viral vector-based vaccine candidate with rVSV-ZEBOV. Both candidates were found to be safe, but a dramatic drop in Ebola incidence in this country is impeding the ability to compare the efficacy of the two vaccines.

Johnson & Johnson and Bavarian Nordic are also developing a two-dose vaccine candidate that employs two different viral vectors. Phase II trials of these candidates are planned for later this year in Uganda, Kenya, and Tanzania. Other trials are also underway.

Many of the current Ebola vaccine candidates were developed years ago, but the relative rarity of Ebola prevented researchers from conducting large efficacy trials. This all changed with the scale of the latest outbreak and researchers reacted quickly. Some candidates received regulatory approval to advance from Phase I to Phase III trials in less than a year. And now that one vaccine candidate appears effective, there are calls from public health organizations to make it available, even as researchers collect more conclusive data on the vaccine’s efficacy.

What scientists ultimately learn from these vaccine candidates could affect other viral diseases, such as AIDS, for which scientists are developing and testing a range of viral vector-based vaccine candidates.

Mary Rushton is a freelance writer based in Cambridge, Massachusetts.