Researchers at the Albert Einstein College of Medicine are working on a new vaccine that may potentially be effective against the two most common forms of herpes virus, HSV-1 and HSV-2 . The findings from the study have been reported in the journal eLife.
Currently, there is no viable vaccine for herpes simplex virus infections. Prior attempts to construct a herpes vaccine have focused on a glycoprotein called gD that is embedded in the virus’s outer envelope. This protein is required for the microbe to enter into and out of cells and to spread from cell-to-cell. gD also elicits a vigorous antibody response that many believe is necessary to produce immunity. However, no gD-based vaccine has proven effective.
Breaking from this approach, researchers created a genetic mutant lacking this protein. In order to test the gD deletion virus as a vaccine, the researchers grew the virus in a cell line that expresses the HSV-1 version of gD. The HSV-2 virus, with gD deleted from its genome, grabbed the available HSV-1 gD proteins from the cell. When introduced to a mouse, HSV-2 was able to use the HSV-1 gD to enter the mouse’s cells. Once inside, HSV-2 replicated abundantly, but because it could not produce gD, future progeny were unable to infect new cells.
The vaccine completely immunized two common strains of lab mice against HSV-2 when challenged with virus intravaginally or on the skin. In fact, no virus could be detected in vaginal washes four days post-challenge and even more importantly, no virus could be found in the nerve tissue, the site where HSV often hides in a latent form only to emerge later to cause disease. Protection against HSV-1, which shares considerable homology with HSV-2, was also demonstrated in both models. The vaccine produced no adverse health effects in a strain of mice with severely compromised immune systems, reflecting the vaccine’s overall safety.
Another of the vaccine’s surprises is how it works. Many vaccines provoke the production of so-called neutralizing antibodies that directly bind and inactivate virus particles. The new vaccine, however, induces antibody-dependent cell-mediated cytotoxicity (ADCC) in which antibodies attach to a virus and flag it for destruction by immune system sentinels such as white blood cells.
The robust response generated by the vaccine, as well as its novel mechanism, has the researchers undertaking additional experiments in mice to determine whether it can be used to treat individuals already infected by HSV-1 and HSV-2. The next step for the researchers in producing a herpes vaccine for use in humans is demonstrating its efficacy and safety in an FDA-approved cell line.
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