Genital herpes is a lifelong infection. Available treatments can manage symptoms but cannot cure or prevent infection. Now, researchers at Yale School of Medicine have taken an important step toward developing a genital herpes vaccine that prevents infection in preclinical models.
In a study published June 19 in Science Immunology, researchers evaluated a two-part vaccination against genital herpes. In this technique, nanoparticles are introduced into the vagina, where a woman’s herpes infection occurs, following an initial part (a typical intramuscular injection, such as the one you receive with a flu shot).
The idea is that the first injection “stimulates” the immune system, and the second topical treatment “pulls” immune activity to the site of the infection. This study extends the original “prime and pull” approach by developing new nanoparticles that effectively induce local immunity.
We have found in preclinical experiments that this approach is a safe way to recruit the right immune cells to the right locations and generate protective immunity. ”
Akiko Iwasaki, lead author, Starling Professor of Immunobiology, Yale School of Medicine
Two-part vaccine for genital herpes immunity
Genital herpes vaccine development efforts have revealed important limitations of common intramuscular injections. This means that a strong immune cell population and antibodies against the herpesvirus are not established in the woman’s vaginal lining, where the virus invades. This limits the scope of the immune attack against the herpesvirus.
To address this challenge, the Iwasaki lab investigated ways to “pull” an immune response into the vaginal lining. The researchers first tested whether introducing chemokines (proteins that can induce immune cells) into the vagina could establish immunity there. This technique led to only partial protection against herpes because it does not involve necessary immune cells called B cells.
Next, they evaluated DNA molecules that stimulate the immune system. The amount of virus in the vagina decreased, but it also caused inflammation.
So the researchers thought they might get the best of both worlds by combining the two methods.
“The lab had these two very promising strategies, but each had some drawbacks,” said Sachin Bagchandani, a postdoctoral fellow in the Iwasaki lab and lead author of the study. “So we set out to formulate particles that could overcome those drawbacks.”
Nanoparticles prevent herpes infection
The result of that research is BEACON (Bioactivity Enhanced Adjuvant Chemokine Oligonucleotide Nanoparticles). The researchers created these nanoparticles by attaching a piece of immunostimulatory DNA to a chemokine.
“Sachin led this research and created stable and effective nanoparticles, which was no small feat,” said Iwasaki, a professor of dermatology and epidemiology and a Howard Hughes Medical Institute investigator.
For this study, the researchers first vaccinated female mice intramuscularly against the herpes virus, then administered BEACON and viral antigen intravaginally. They found that BEACON established a strong immune cell and antibody response against the herpes virus in vaginal tissue that lasted for a long time, at least six months.
When exposed to the herpesvirus, mice that received the “prime-and-pull” treatment were highly resistant to infection, with 80% showing no signs of disease for more than six months. This compared to only 40% in mice that received intramuscular injections only.
“This showed that this approach has the potential to have a very large impact and establish a fairly long-lasting local immune response,” Bagchandani said.
Additionally, BEACON allowed researchers to target the right cells to generate immunity, rather than broadly affecting all cells. This means that less DNA molecules were needed than those used in previous experiments, and this small amount prevented the development of inflammation.
“This formulation is quite remarkable in that respect,” Iwasaki said.
vaccine for humans
Researchers are currently evaluating whether this “prime-and-pull” technique can be used to: handle As well as preventing infection. They’re also thinking about what this looks like for people.
“We are collaborating with the Appel lab at Stanford University to see if BEACON can be made into a translatable formulation, such as a vaginal suppository,” Bagchandani said. “We are also looking at a nasal approach that involves a ‘pull’ inside the nose, which could make this type of treatment more effective for men as well.”
In a further step, the researchers aim to test the method in human clinical trials, with the ultimate goal of developing a vaccine for humans.
“Much of the suffering that patients experience is not only physical, but also mental and social,” says Dr. Iwasaki. “But so are viruses. Whether it’s the flu, Epstein-Barr virus, or herpes simplex, it’s not the person’s fault that they got it. And yet there’s a lot of stigma. We hope that these kinds of strategies will prevent diseases that seriously impact people.”
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Reference magazines:
Bagchandani, S.H.others. (2026). Bioactive enhanced adjuvant chemokine oligonucleotide nanoparticles (BEACON) for mucosal vaccination against genital herpes. Science Immunology. DOI: 10.1126/sciimmunol.aea6419. https://www.science.org/doi/10.1126/sciimmunol.aea6419
