Zika virus: the fight continues
DNA vaccine against Zika virus has successfully passed the first phase of clinical trials
Anna Kaznadzei, N+1
Biologists from the University of Pennsylvania and their colleagues from the Wistar Institute, Inovio Pharmaceuticals and GeneOne Life Science have developed a new generation vaccine against Zika fever. The DNA vaccine showed high efficacy in the first phase of clinical trials, successfully initiating the synthesis of specific antibodies in the subjects. The study was published in the New England Journal of Medicine (Tebas et al., Safety and Immunogenicity of an Anti–Zika Virus DNA Vaccine – Preliminary Report).
Zika fever is a disease caused by an RNA virus from the Flaviviridae family. Its carriers are mosquitoes of the genus Aedes, although there are cases when it has been transmitted sexually or from mother to fetus. The Zika virus was first discovered in 1947 in rhesus monkeys living in the Zika forest in Uganda. In the following decades, several cases of human infection with the virus were recorded in Africa and Southeast Asia, but the disease did not cause serious consequences - most of the patients did not have symptoms of the disease, and in case of their manifestation, the disease proceeded relatively mildly and was not fatal. Over the course of sixty years, only a dozen and a half cases of Zika fever have been registered.
In 2007, an epidemic broke out in Micronesia, and after the 2013-2014 outbreaks in French Polynesia, the virus spread rapidly in Central and South America. At the beginning of 2016, there was evidence that the Zika virus can cause microcephaly in newborns if their mothers suffered an infection during pregnancy. It affects the precursor cells of brain neurons, causing their death. The greatest concern is the correlation of the Zika pandemic with the spread of cases of microcephaly and some other defects in newborns in the relevant territories.
DNA vaccines are artificially synthesized short ring DNA (plasmids) carrying genes encoding, in this case, viral envelope proteins. Such proteins are not contagious and are not dangerous in themselves, but their synthesis inside the body makes it possible for the immune system to learn to recognize them. In response, the corresponding specific antibodies are synthesized, which prevent the disease in case of a real infection. At the same time, scientists note, DNA vaccines can be produced fairly quickly and in large quantities, they are safe and have high stability.
The study began in August 2016. The vaccine, called GLS-5700, was administered subcutaneously to 40 test participants (average age 38 years) three times – in the first, fourth and twelfth week of the study. The participants were divided into two groups, the vaccines in the groups differed in the amount of DNA (1 or 2 mg). The injection site was then treated with a Cellectra device, which increased the effectiveness of the introduction and perception of the vaccine by the body due to small directed electrical stimuli (this method is called electroporation).
Two weeks after the third dose was administered, all project participants developed specific antibodies to the Zika virus. In 60 percent of cases, these antibodies demonstrated a virus-neutralizing effect on a panel of Vero cells (a culture of African green monkey renal epithelial cells). In 70 percent of cases, 90 percent inhibition of nerve cell culture infection was shown, in 95 percent of cases, 50 percent inhibition. At the same time, there was no correlation between these numbers and the initial amount of the vaccine administered.
In order to find out how successfully such antibodies can fight infection in vivo, the blood serum of the subjects was injected into mice with impaired immunity (the alpha and beta interferon genes were deleted in them). It turned out that the serum successfully protected most of the mice (103 out of 112) from infection with the virus.
Separately, scientists note that the vaccine did not cause side effects and was normally perceived by the human body, but these aspects will have to be studied in more detail in the next phases of clinical trials.
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