A team of scientists at the University of Pennsylvania has developed a new vaccine candidate to protect against herpes simplex virus type 2 (HSV-2), the most common sexually-transmitted disease.
Using a fluorescein isothiocyanate (FITC) conjugated immunoglobulin staining technique, and under direct immunofluorescence (DIF), this tissue sample extracted from a vesicle and ulcer, reveals the presence of herpes simplex antigen in a patient determined to have HSV-2 infection. Image credit: Craig Lyerla / CDC.
HSV-2 is a sexually transmitted infection with 14% prevalence among 15- to 49-year-old persons in the United States and 11% globally.
Individuals remain infected for life, with periodic clinical recurrences that may be painful or subclinical recurrences that risk transmission of infection to intimate partners and newborns.
Genital herpes increases the risk of acquisition and transmission of HIV by three- to fourfold, highlighting the need for an effective vaccine.
“Along with physical symptoms, HSV-2 takes an emotional toll,” said University of Pennsylvania’s Professor Harvey Friedman, corresponding author of the study published in the journal Science Immunology.
“People worry over transmission of the disease, and it can certainly have a negative effect on intimate relationships.”
In the study, Professor Friedman and colleagues delivered vaccine to 64 mice and then exposed them to HSV-2.
After 28 days, 63 of the mice were found to have sterilizing immunity, meaning there was no trace of herpes infection or disease after the exposure. The one remaining mouse developed dormant infection without any prior genital disease.
Similarly, 10 guinea pigs, which have responses to herpes infections that more closely resemble that of humans, were also given the vaccine and exposed to the virus.
No animal developed genital lesions and only two showed any evidence that they became infected, but the infection was not in a form that animals could transmit the virus.
“We’re extremely encouraged by the substantial immunizing effect our vaccine had in these animal models,” Professor Friedman said.
Building on the approaches of many cutting-edge cancer and immunotherapy researchers, Professor Friedman’s team filled their vaccine with specific messenger RNA (mRNA), which can create proteins necessary for a strong immune response.
This vaccine stimulates three types of antibodies: one that blocks the herpes virus from entering cells, and two others that ensure the virus doesn’t ‘turn off’ innate immune system protective functions.
This approach differs from other herpes vaccines, which often only rely on blocking virus’ entry as the mode to attack the virus.
“Based on the results, it is our hope that this vaccine could be translated into human studies to test both the safety and efficacy of our approach,” Professor Friedman said.
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Sita Awasthi et al. 2019. Nucleoside-modified mRNA encoding HSV-2 glycoproteins C, D, and E prevents clinical and subclinical genital herpes. Science Immunology 4 (39): eaaw7083; doi: 10.1126/sciimmunol.aaw7083
