24 September 2019

HSV-2 vaccine

New vaccine protects mice and guinea pigs from genital herpes

Maxim Abdulaev, N+1

Scientists have tested a vaccine against the herpes simplex virus of the second type, which causes genital herpes. Experiments on mice and guinea pigs have shown that the vaccine, created on the basis of RNA, which encodes three viral proteins, protected 100 percent of animals from genital lesions. Now the remedy needs to be tested in humans. The test results are described in the journal Science Immunology (Awasthi et al., Nucleoside-modified mRNA encoding HSV-2 glycoproteins C, D, and E prevents clinical and subclinical genital herpes).

The herpes simplex virus of the second type causes diseases of the genitals. Once it enters the body, it no longer leaves it, remaining in the cells of the nervous system, and it is very common in the world: about 11 percent of the entire population of the planet has the virus, and in Russia about 19 percent of the population is infected with it. There is still no effective vaccine for the disease, and treatment only helps to reduce the severity and duration of relapses.

Previous attempts to create a vaccine against the virus were not entirely successful: drugs based on two or three viral glycoproteins helped protect up to 100 percent of laboratory mice from clinical manifestations of genital herpes, but could not stop the replication (reproduction) of the virus.

Harvey M. Friedman and his colleagues from the University of Pennsylvania have created and tested a new vaccine that is based not on viral proteins, but on viral RNA encoding the same viral glycoproteins: D (gD2), C (gC2) and E (gE2). Tests of this trivalent vaccine were carried out first on mice, and then on guinea pigs.

For the experiment, the mice were divided into four groups: in one there were mice vaccinated with a drug with three viral RNAs, in the other with only one RNA, and in the third there were animals that were vaccinated with a protein vaccine. Another group was a control group, not protected by anything from the virus.

Mice were infected intravaginally 28 days after vaccination and watched how the infection develops. Already on the second day after infection, there were no viruses in the vaginal culture of mice from the first group, whereas in groups vaccinated with only one RNA or protein vaccine, there were viruses, although their number decreased on the fourth day. The virus was present in three out of twenty mice in the group with an RNA vaccine of one gene and in two out of ten in the group with a protein vaccine. All ten mice from the control group had viruses in the vaginal culture and developed extensive genital lesions. None of the animals protected by the trivalent RNA vaccine had genital lesions.

herpes.jpg

The presence of viruses in the vaginal culture of mice on the fourth day after infection (figure from an article in Science Immunology).

Polymerase chain reaction (PCR) analysis, which reveals sequences of nucleic acids specific to the pathogen, nevertheless showed the presence of viral DNA even in mice with an RNA vaccine for three antigens, and its number decreased from the second to the fourth day. Since the infection was not spreading at that time, the scientists concluded that PCR showed the presence of DNA of degrading viruses that had already been neutralized by antibodies and were unable to reproduce.

After that, the test was carried out on guinea pigs. This time, on the second day, viruses were detected in the vaginal culture in five out of ten animals in the group with trivalent RNA vaccine, but on the fourth day, viruses in this group were no longer detected in any guinea pigs. After four days, viruses were detected in only two animals in the protein vaccine group and in nine out of ten subjects in the control group. As in the test with mice, all animals with trivalent RNA vaccine avoided genital lesions.

Mice and guinea pigs were observed for another 50 days, waiting for the virus to reappear after it disappeared immediately after infection. In 50 days, this happened in two percent of mice from the group vaccinated with trivalent RNA vaccine, and in 20 percent of guinea pigs with the same vaccine. In groups of animals vaccinated with protein vaccine, the virus reappeared in 27 percent of mice and 50 percent of guinea pigs.

As the authors summed up, the new trivalent RNA vaccine protected 100 percent of experimental animals from genital lesions and 80 percent from hidden, asymptomatic spread of the virus. This, as the scientists write, makes the new vaccine a good candidate for future human trials.

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