Victory over Ebola
Maxim Russo, <url>
In January, we talked about the beginning of field clinical trials of a number of vaccines against the virus that causes Ebola. Recently, the results obtained during these tests were announced. And the results are encouraging. Separately, it is noteworthy that thanks to a special test method, they were able to conduct them in record time.
A clinical study conducted in Guinea showed that people who were given one dose of the vaccine receive one hundred percent protection from infection with Ebola when they come into contact with patients starting from the 10th day after injection. The test results are presented in the Lancet journal (Henao-Restrepo et al., Efficacy and effectiveness of an rVSV-vectored vaccine expressing Ebola surface glycoprotein: interim results from the Guinea ring vaccination cluster-randomized trial). Director of the Center for Research in the Field of Infectious Diseases Michael Osterholm, commenting on this news, said that it will go down in history as a landmark event in the field of public health and will then be studied in schools (Science, Ebola vaccine works, offering 100% protection in African trial).
The vaccine that showed such a remarkable result is called VSV-EBOV. Recall that it was created in the National Microbiological Laboratory of Canada, part of the structure of the National Health Agency. The virus of vesicular stomatitis of cows (Indiana type virus) was used to create the vaccine. In cows, this disease causes bubble rashes on the mucous membrane of the mouth, and people carry the disease easily, feeling only a slight malaise. After the transferred disease, immunity arises. The developers have provided the vesicular stomatitis virus with surface proteins of the Ebola virus, ZEBOV type, Zaire, which is characterized by the highest mortality. In parallel, they created another modification of the vaccine, where the vesicular stomatitis virus had proteins of another dangerous virus that causes Marburg hemorrhagic fever.
In 2005 – 2009, three trials of the vaccine were conducted on animals (crab-eating macaques), funded by the Governments of Canada and the United States. They have shown that the vaccine provides them with reliable immunity from Ebola or Marburg fever, depending on what kind of virus they received. The vaccination itself was asymptomatic. Moreover, data were obtained on the effectiveness of the vaccine even in cases when the animal was already infected with the virus at the time of its receipt.
There were concerns about reports by a number of researchers that the virus of vesicular stomatitis of cows can in some cases cause damage to the nervous system in monkeys, rodents, cows, sheep and horses. To test both Ebola and Marburg vaccines, healthy crab–eating macaques were injected into the hypothalamus, seven monkeys for each vaccine. Three more monkeys were injected with an unmodified vesicular stomatitis virus into the hypothalamus. As a result, all 14 macaques whose brains were injected with the vaccine felt fine, while three who received the original virus developed severe neurological symptoms. From this, the researchers concluded that the neurovirulence of the vesicular stomatitis virus is eliminated when it is modified.
The duration of the vaccine's action is also checked. At the moment, a study has been published in which the efficacy of the vaccine (in the Marburg variant) was tested 14 months after administration. Vaccinated macaques did not get infected with the virus, while two control animals died.
In 2010, the National Health Agency of Canada issued a license to a small American company NewLink Genetics to develop the VSV-EBOV vaccine for human use. The role of this company was mainly to organize clinical trials in the United States, it does not have sufficient capacity to produce large quantities of the vaccine. Later, a license from NewLink Genetics was acquired by one of the major pharmaceutical companies Merk Inc. for $ 50 million.
Interestingly, the vaccine seems to be effective regardless of the method of its introduction into the body. In one study on crab-eating macaques, four animals received the vaccine orally, four in the form of nasal drops and two more by intramuscular injections. After 28 days, all the monkeys were infected with the Ebola virus (ZEBOV). None of them got sick.
The researchers even tested the effectiveness of the vaccine in case of infection with the Ebola virus by inhalation of an aerosol. So far, there have been no such cases of infection in a natural setting, but we decided to check the possibility for the use of an aerosol with the Ebola virus by terrorists. During the test, monkeys were infected with Ebola or Marburg viruses in this way. All vaccinated monkeys survived it, the unvaccinated ones got sick and died.
In October 2014, the US National Institute of Allergy and Infectious Diseases (NIAID) recruited healthy volunteers to conduct the first phase of a clinical trial of the vaccine, which determined its optimal dosage and checked for possible side effects. The study was conducted by NewLink Genetics on the basis of the Walter Reed Army Institute of Research, the largest biomedical research center of the US Department of Defense. The National Health Agency of Canada then donated 800 doses of the vaccine to WHO for larger trials that were conducted in Switzerland, Germany, Gabon and Kenya. The work was almost stopped, as the test participants began to have side effects: fever, weakness and joint pain. But then, because of the great danger of Ebola, it was decided to continue the study of the vaccine.
The vaccine trials in Africa were led by Ana Maria Henao-Restrepo from the World Health Organization. They were also attended by the Norwegian Institute of Public Health, the Ministry of Health of Guinea, the London School of Hygiene and Tropical Medicine, Doctors Without Borders, Wellcome Trust. Since the Ebola epidemic in West Africa was already on the decline at the end of 2014, it was quite difficult to recruit enough participants for a double-blind study, so "ring vaccination" was chosen as the design of the study, when people who have been in contact with a person who has a new case of the disease, as well as the second circle is those who have been in contact with these people. In 48 such "rings", vaccination was carried out immediately after the disease was detected. In 42 rings, people received the vaccine three weeks later. Later, it was calculated how many cases of the disease occurred among these people, starting from the tenth for after vaccination. In 2014, people vaccinated quickly did not have a single Ebola disease. Among the 2,380 people who received the vaccine after three weeks, 16 became ill.
The unusual method of conducting the test was the reason that WHO was the main organizer of the study (no one else wanted to take on such responsibility). The idea of ring vaccination made it possible to conduct a study in a short time. If the organizers had conducted a standard randomized controlled trial, then, as Michael Osterholm notes, they would still not have received a result. In fact, they have traveled a path in a year that usually takes a decade. Previously, a similar approach was used in smallpox vaccine trials.
Of course, not all the problems associated with the development of a vaccine have been solved at the moment. The study did not involve children, adolescents and pregnant women, as the safety of the vaccine was not proven for them. Such a study on healthy children was recently successfully completed in Gabon, and now they will also receive the vaccine.
Social factors should also be taken into account. The population of rural Guinea does not always readily agree to vaccination. Doctors were able to give a dose of the vaccine to only half of the people involved in the "rings".
The organizers plan to continue testing the vaccine in Guinea, as well as expand their activities to cover Sierra Leone, where new cases of the disease also continue to be observed. Johnson & Johnson Janssen Pharmaceuticals (a division of Johnson & Johnson Corporation) is still unclear what will happen to the other two Ebola vaccines that are being developed by GlaxoSmithKline and Janssen Pharmaceuticals. The number of cases continues to decline and it is very likely that there simply will not be enough patients to conduct full-fledged trials of these vaccines in the conditions of a fading epidemic. At the beginning of the year, for this reason, tests of one of the antivirus tools were already discontinued.
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09.08.2015