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Study: Experimental dengue vaccine protects all recipients in virus challenge

The Aedes aegypti mosquito, carrier of Dengue fever. (Image Courtesy: Google)

A clinical trial was being conducted among the volunteers who were being affected with the virus six months after receiving either an experimental dengue vaccine which is being developed by the scientists of the National Institute of Health or a placebo injection yielded quite contrasting results. All of the 21 volunteers, who were receiving the vaccine named TV003, were protected from the infection while all the 20 placebo recipients had developed the infection.

The study being conducted is being published in the Journal Science Translational Medicine, which underscores the importance of the human challenge studies, in which the volunteers were being exposed to the disease causing pathogens under different carefully controlled conditions.

Response of transgenic mosquitoes to challenge with dengue virus serotype 2 (DENV-2). (Image Courtesy: Google)
Response of transgenic mosquitoes to challenge with dengue virus serotype 2 (DENV-2). (Image Courtesy: Google)

Background of the Research

Stephan Whitehead, Ph.D of the NIH’s National Institute of Allergy and Infectious Diseases commenting over the same says that, the findings which are obtained from this trial are quite encouraging for those who had been working over the vaccine candidates over the years, a disease which is a significant burden to much of the world. This finding has informed that the recent decision being obtained by the officials at the Brazil’s Butantan Institute to advance the TV003 vaccine in the large phase of the 3 efficacy trial.

Fever of the Dengue which is being prevalent throughout the tropics and subtropics can be caused by any of the dengue viruses which are called serotypes and are being spreaded by the Aedes mosquitoes which is the same mosquito being responsible for the spread of the Zika Virus. It has been found that about 390 million people who are being infected by the Dengue virus annually, develops either no symptoms or milder illness. Some of the patients are also being found developing serious or the life-threatening illness and the larger outbreak is being seeking millions for seeking the care.

Classification of dengue virus vaccine candidates. (Image Courtesy: Google)
Classification of dengue virus vaccine candidates. (Image Courtesy: Google)

Trials of the Dengue Vaccine

Higher the prevalence of the natural dengue infections in the endemic areas means that many of the people has undergone through the infection at some point of the time. Thus they have developed a partial immunity for the infection. This higher degree of partial immunity being developed makes it difficult for checking the efficacy of the candidate to the dengue vaccine. The experimental vaccine was being primarily being developed by Dr. Whitehead and his colleagues at the NIAID’s laboratory of infectious diseases. Scientists from different departments like U.S. Food and Drug Administration has also contributed for the development of the vaccine. The vaccine is being developed from four of the live weakened viruses being targeted at each of the four serotypes.

A total consisting of the 48 healthy volunteers have participated in the test for receiving either the vaccine or the placebo injection. They have enrolled at two of the trial sites, the University of Vermont College of Medicine, Burlington and Johns Hopkins Bloomberg school of Public Health, Baltimore. About 41 of them returned after duration of six months with the dengue virus. Dr. Whitehead and his colleagues also developed the challenge virus in the trials which were the modified version of the dengue-2 serotype virus which was being isolated from the Kingdom of Tonga in 1974. The original virus dose only caused the volunteers to develop mild illness while the previous dose caused all the recipients to develop viremia – the presence of the virus in the blood and most of them even developed mild rashes.

Challenge Virus: Effectiveness

Dr. Whitehead commenting over the study says that, this particular modified dengue virus is quite attractive one which is being causing it to reliably induce the dengue infection in a very high percentage without causing serious illness. A human challenge model rather than the illness is one of the important characteristic, explains Anna Durbin, MD, who has led the clinical trial at the Johns Hopkins. Adding to the same she says as the dengue virus is not having any of the specific therapies it is quite desirable for the development of the challenge virus which can develop viremia following the exposure to the challenge virus. It will enable lesser number of people to enroll in the trials still achieving the results about the effectiveness of the vaccine against the virus.

In this study about 20 of the placebo recipients developed the viremia, 16 percent of them had developed a mild rash and four of them had a temporary drop in the white blood cells count. It is quite notable that none of the 21 recipients of the TV003 developed viremia or any signs of the infection after the challenge. Dr. Durbin says that they were quite surprised to see that this particular candidate vaccine provided complete protection to those receiving it. The Dengue-2 serotype is considered as relatively weaker component in this. So to determine its ability to confer the protection against the dengue-2 serotype was quite encouraging.

Dr. Whitehead is being currently developing the human challenge model using the modified dengue serotype-3. This challenge would then be used in the future clinical tests for the testing of the candidate’s efficacy to the dengue vaccines or therapies. Dengue virus is in the same virus family as that of the Zika Virus and NIAID team is now leveraging their experience with the life-attenuated dengue vaccine in the efforts for developing the Zika Vaccine, noted Dr. Whitehead.

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