Zika virus vaccine tested on animals

One injection of RNA vaccine prevented mice and macaques from contracting Zika virus

Oleg Lischuk, N+1

American, Canadian and German scientists have developed an RNA vaccine against Zika fever. In the experiment, one dose of the drug provided mice and monkeys with long-term protection against infection with the virus. The results of the work are published in the journal Nature (Pardi et al., Zika virus protection by a single low-dose nucleoside-modified mRNA vaccination).

Zika fever is caused by a virus related to the causative agent of Dengue fever. It was first isolated in Africa in 1947, but until recently only small local outbreaks of the disease were recorded. In the spring of 2015, a large-scale epidemic of Zika fever began in Brazil, which spread to dozens of countries.

In most cases, the disease is asymptomatic, in others it is manifested by a slight rise in temperature and general malaise, which pass independently for several days. Very rarely, fever is severe or leads to the development of neurological complications. The greatest danger of the virus is that when pregnant women are infected with their children, the risk of microcephaly (underdevelopment of the brain and cranial box) and other congenital lesions of the central nervous system sharply increases. An effective treatment for Zika fever has not yet been found, so the greatest hopes are pinned on the development of a preventive vaccine.

Employees of the University of Pennsylvania and the US National Institutes of Health with colleagues from other research centers have developed a vaccine against infection based on matrix RNA (mRNA). She was chosen for several reasons. Firstly, mRNA serves as a non-infectious gene vector that effectively expresses a given protein without embedding it into the genome of cells. Secondly, it is quite easy to establish its large-scale cost-effective production. And, thirdly, even a small dose of such a drug causes a pronounced immune response.

The vaccine created by scientists is an mRNA encoding premembrane and envelope glycoproteins (prM-E) of the ZIKV H/PF/2013 virus strain. This mRNA contains a modified nitrogenous base 1-methylpseudouridine (m1Ψ), which prevents the immune system from attacking the vaccine and increases the level of mRNA translation in a living organism. The vaccine molecules are encased in lipid nanoparticles, which also contribute to effective and long-lasting translation.

In the experiment, subcutaneous administration of 30 micrograms of the drug (ZIKV prM-E mRNA-LNP) to mice caused a pronounced immune response (production of key immune mediators by helper T-lymphocytes and immunoglobulin G virus-specific protein by B-lymphocytes). The vaccine effectively prevented Zika virus replication in all nine vaccinated animals two weeks and five months after infection. In eight out of nine mice from the control group, contact with the virus led to infection.

After that, the drug was tested on rhesus monkeys, to whom it was administered at a dose of 50 micrograms. When the Zika virus was introduced five weeks after infection, four out of five vaccinated animals had no detectable concentrations of the pathogen in the blood, one had a short-term and insignificant (100 copies per milliliter) presence of the virus on the third day after infection. In all six monkeys from the control group, concentrations of the pathogen up to 7000 copies per milliliter were determined in the blood.

"The vaccine works equally well in mice and macaques, so we think it will work just as well in humans," said one of the authors of the work, Drew Weissman, and added that the team expects to start clinical trials within 18 months.

To date, more than a dozen candidate vaccines against Zika fever have been developed, but none of them are based on mRNA. All of them are at different stages of preclinical testing. In June 2016, the U.S. Food and Drug Administration (FDA) approved the first clinical trials of the experimental vaccine GLS-5700, which is a synthetic DNA construct (plasmid) that acts on several viral antigens.

Portal "Eternal youth" http://vechnayamolodost.ru  06.02.2017