Based on a genetically modified form of the herpes virus, this vaccine would block its ability to take refuge in the nervous system to escape the body’s immune response.
- The vaccine uses a modified version of the herpes virus, then unable to take refuge in the nervous system.
- Mice vaccinated and infected with a virulent strain of sexually transmitted HSV-2 showed less genital lesions, less viral replication and less viral shedding.
Caused by the Herpes Simplex Virus (HSV), herpes is a common infectious disease that can affect different parts of the body, starting with the lips and genitals and, in the most severe cases, the eyes. In France, it is estimated that 10 million people are affected by herpes labialis, 2 million by genital herpes, and 60,000 by ocular herpes.
If it is possible to control the effects of herpes, in particular thanks to antiviral creams, our body never gets rid of the virus. The latter alternates between sleep phases in nerve cells and outbreaks, usually caused by stress, during which it is particularly virulent. And, despite the prevalence of HSV, more than four decades of research have yet to yield a herpes vaccine.
A new study conducted by the University of Nebraska-Lincoln (USA) and published in the journal Vaccinated raises these days the hope of a vaccine against the Herpes Simplex Virus.
Countering immune difficulties
The researchers behind this new vaccine candidate have spent years studying how to prevent HSV from reaching the nervous system. They discovered that a certain protein in HSV, called pUL37, travels along nerve fibers to help it infiltrate nerve fibers and the sensory core. Computational analyzes based on this architecture suggested that three regions of the protein may prove important for the process.
To prevent the virus from invading the nervous system, the researchers therefore removed and replaced five codons, that is to say the fundamental coding information of DNA, in the viral genome of each region. They then injected this modified virus into mice. They then found that, rather than advancing deep into the nervous system, the virus was blocked at the nerve ending.
But, if the virus could not take refuge in the nervous system, this genetic modification of HSV also had consequences on the immune response. “When you knock the virus down to the point that it doesn’t replicate well, you’re not rewarded with a robust immune response that can protect you from future exposures”explains Gary Pickard, co-author of the work.
Less replication and less viral shedding
However, it seems possible to circumvent this pitfall: by injecting the modified virus into region 2, or R2, of the pUL37 protein. By testing this alternative in mice, the researchers found that the modified R2 form of HSV-1 showed encouraging results. They weren’t sure, however, that a vaccine against HSV-1 would be up to the task of generating immunity against HSV-2.
Only one of twelve guinea pigs vaccinated with R2 developed acute lesions after being injected with HSV-2. And unlike guinea pigs who received no vaccine or another vaccine candidate, those who received the R2 vaccine showed no signs of HSV-2 in the group of brain cells that normally harbor it. Neutralizing antibodies, meanwhile, were recorded about three times more often in guinea pigs vaccinated with the R2 vaccine than in those vaccinated with the other candidate vaccine.
“The fact that viral shedding was so reduced with the R2 vaccine is really important, because it’s viral shedding – even if it doesn’t cause damage – that can then transmit the virus, says Professor Pickard. Sf you have genital herpes, you can pass it on to your loved ones without knowing you have it. It is very problematic. So the fact that shedding has been so high is a very good sign.”
Pending human clinical trials, researchers are now working on vaccines for livestock, including cattle and pigs, susceptible to HSV.
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