The first herpes simplex viruses or HSV cause cold sores and genital infections, and they’re doubly unpleasant because the virus is carried for life within the nervous system.
And this allows it to reactivate periodically to cause new infectious skin lesions that are also exquisitely painful. And despite years of effort, scientists have not yet developed and effective vaccine to block the infection.
But now, by removing a component of the virus, a protein called GD, experts have made viruses that can completely protect animals with either cold sore (HSV Type – 1) or HSV – 2, the genital variants.
The primary strategy that people use in the past focused on one major protein that the virus makes, like a protein D. That protein induces high levels of antibodies and antibodies usually protect you from infection.
But in the case of the herpes simplex viruses, these antibodies protected animal models from infection but did not appear to infect humans. So the experts thought that maybe those antibodies are interfering in some way with making the kind of immune response that would be more protective. So they deleted that protein from the virus.
How Then was the Protein Grown?
Glycoprotein D is essential for the virus to get into cells, so the researchers grew it in a cell line that provided the HSV – 1 Glycoprotein D. That just provides the glycoprotein on the outer surface of the viral envelope, allows the virus to get in.
But once that virus is inside the cell, it doesn’t have the DNA to make more than that protein. And therefore it also doesn’t continue to spread and doesn’t cause any disease.
So you get effectively a replication defective virus gets in and hits the cells once but nonetheless expresses all the panel of genes that HSV normally express showing to the immune system that it is a genetic hand. This leads to the creation of a diverse immune system response.
What does this do to the Animal Being Infected with wild-type like a normal virus that does have GD?
The question is whether this can act as a protective vaccine. So when the researchers took mice and immunize them with it and then challenged with a very high dosage of wild-type virus, we observe 100% complete protection.
Not only do the researchers protect them with the disease, but unlike the previous vaccine candidates researchers were able to prevent the virus from establishing what they call “latency.” This is the ability of the virus to hide out from inside your nerve cells and therefore cause persistent or recurrent infections. And this vaccine has completely prevented that.
Does the virus prevent the ability of the agent to replicate on the mucosal surface and for that reason, it cannot access the nervous system? Or was there some other reason why it was disabled in its ability to get into the nervous system?
To answer that question, the researchers did another type of experiment wherein they tried to answer whether the immune system the vaccine is inducing was mediated by antibodies (T cells), the other half of the immune system of animals, they will completely protect it.
That told researchers that it was those antibodies. The researchers then used those antibodies and looked to see whether they got into the sites of infection.