Public health

Ebola vaccine offers hope

Print edition : September 04, 2015

Ebola virus. Photo: NYT

Lijun Rong, UIC professor of microbiology and immunology. Photo: Jenny Fontaine

AN international team of researchers led by Ana Maria Henao-Restrepo of the World Health Organisation (WHO) has, in a ring vaccination trial, found that a single dose of a live candidate Ebola vaccine prevented all infections among contacts more than six days after vaccination. The results have been published in the latest issue of Lancet.

Several candidate Ebola vaccines have been developed. One of them—a recombinant, vesicular stomatitis virus-based preparation expressing the glycoprotein of a Zaire Ebolavirus (rVSV-ZEBOV)—has been found to cause transient systemic infection and induce rapid immune response against the Ebola virus surface protein.

In an open-label, cluster-randomised, ring vaccination trial in Guinea in 2015, investigators administered a single intramuscular injection of rVSV-ZEBOV to the contact networks of patients with confirmed Ebola virus disease (EVD) immediately after the identified exposure or 21 days later. Non-pregnant adults with contact during the preceding 21 days were eligible. The number of individuals a cluster was 58 to 100.

The ring vaccination strategy is based on the approach used in the 1970s to eradicate smallpox. It involves the identification of a newly diagnosed and laboratory-confirmed case of EVD and the tracing of people who have been in contact with that patient. These people and their contacts, often family members, neighbours, colleagues and friends of the patient, constitute the “ring”. The rings are selected at random.

In the interim analysis of infections up to July 20, 2015, it was seen that among 2,014 vaccinees (48 clusters) in the immediate-vaccination group, there were no cases of EVD with onset of symptoms in ≥ 10 days after randomisation, for an efficacy of 100 per cent. In the delayed-vaccination group (2,380 eligible—but not necessarily vaccinated—people, 42 clusters), 16 cases of EVD occurred. No vaccinees in either group developed EVD in ≥ six days after immunisation.

Among all 5,415 vaccination-eligible contacts and contacts of contacts (vaccination rates, 42-49 per cent), six immediate-group participants and 16 delayed-group participants developed EVD, for an estimated vaccine effectiveness of 75 per cent. Only one serious vaccine-related adverse event (fever, followed by full recovery) was observed.

Mary E. Wilson of GeoSentinel Surveillance Network, reviewing the work, commented: “The findings of this interim analysis suggest that rVSV-ZEBOV might be highly efficacious and safe…. Because the vaccine is live, it can rapidly induce immunity; however, some individuals will be unable to receive it…. In an outbreak situation, rVSV-ZEBOV could potentially be employed early to control spread in a population.”

Meanwhile, researchers at the University of Illinois at Chicago (UIC) have found that a well-known class of molecules, many of which are already in use therapeutically, may be able to block the Ebola virus’ entry into cells and halt the disease in its tracks. The paper reporting the findings is due to appear in Journal of Virology.

Ebola and the closely related Marburg virus are among the most lethal in the world, both highly contagious and deadly. “We know very little about the basic biology of these diseases,” said Lijun Rong, UIC microbiologist and immunologist and the principal investigator.

Rong and associates found that Ebola and Marburg viruses both use gateways called G protein-coupled receptors, or GPCRs, to enter a cell after attaching to its surface. They believe that blocking entry with a drug that ties up the receptor may prove to be an effective therapy.

“These G protein-coupled receptors are a big family of closely related molecules in humans, altogether probably more than a thousand,” said Rong. Because GPCRs are involved in many human diseases, he said, a host of drugs have already been developed that target them.

According to him, in the history of therapeutics, about half of our drugs were developed to target GPCRs. For example, a number of antihistamines used as allergy medications are GPCR receptor antagonists.

The researchers screened approximately a thousand compounds using a high-throughput screening facility. They found that 20 GPCR antagonists, or molecules that block GPCR receptors, were able to block Ebola and Marburg viruses from entering cells. Learning how the two viruses infect cells and how they can be blocked offers the hope of finding therapeutics to combat both deadly diseases, Rong said.

“There are a lot of drugs and compounds that work through this mechanism, acting as antagonists to GPCR receptors,” he said. “This gives us a huge repertoire that can be tested against Ebola/Marburg.”

R. Ramachandran