Herpes simplex virus (HSV) is a widespread viral infection. It manifests in two primary forms: herpes simplex virus type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2). While HSV-1 is often associated with oral herpes (cold sores) and HSV-2 typically causes genital herpes, both types can infect either area.
An estimated 3.8 billion people under 50 globally (64% of this demographic) carry HSV-1. Additionally, about 520 million people aged 15 to 49 worldwide (13% of that age group) are living with HSV-2. Many individuals with HSV experience no symptoms, yet the virus remains present in their bodies.
Understanding Herpes and Its Persistence
Herpes simplex virus infections can cause fluid-filled blisters that appear around the mouth, on the genitals, or in other areas. Before these blisters emerge, some people may feel a tingling, itching, or burning sensation in the affected area. Initial outbreaks can also be accompanied by flu-like symptoms, such as fever, swollen lymph nodes, and body aches.
The herpes virus establishes latency within nerve cells. After the initial infection, the virus travels from the skin or mucous membranes to nearby nerve cells, where it becomes mostly inactive. This latent state means the virus is present but largely dormant, residing in nerve ganglia, such as the trigeminal ganglia for oral herpes or the sacral ganglia for genital herpes.
The virus can periodically reactivate from these nerve cells, leading to recurrent outbreaks of blisters and sores. This ability to hide within the nervous system makes herpes particularly challenging to cure. The latent virus is shielded from the body’s immune response and from current antiviral medications, which primarily target active viral replication.
Managing Herpes Today
Current medical approaches for herpes primarily focus on managing symptoms and reducing the frequency and severity of outbreaks. Antiviral medications, such as acyclovir, valacyclovir, and famciclovir, are the standard of care for treating HSV infections. These drugs work by interfering with the virus’s ability to replicate, thereby shortening the duration of outbreaks and helping to alleviate discomfort.
These antiviral treatments can be used episodically at the first sign of an outbreak or as suppressive therapy for individuals who experience frequent recurrences. While effective in controlling the active virus and reducing the risk of transmission, these medications do not eliminate the latent virus from the nerve cells. Consequently, they do not offer a permanent cure for herpes.
Research Pathways to a Cure
Researchers are actively exploring several innovative strategies to achieve a cure for herpes, focusing on eliminating the latent virus or providing long-lasting protection. These efforts represent a significant shift from mere symptom management to potential eradication. Various research institutions and pharmaceutical companies are pursuing different avenues, from gene editing to novel vaccine technologies and new antiviral compounds.
Gene therapy represents a promising frontier in the quest for a herpes cure. Scientists at the Fred Hutchinson Cancer Center are investigating an experimental gene therapy that uses molecular scissors, called meganucleases, to target and cut the viral DNA within infected nerve cells. These meganucleases are delivered to the nerve cells using modified adeno-associated virus (AAV) vectors. Preclinical studies in mouse models have demonstrated significant success, showing a reduction of 90% or more in latent HSV-1 DNA, and up to 97% reduction for HSV-2. This approach aims to damage the viral DNA beyond repair, prompting the body’s own cellular repair systems to eliminate it, thereby targeting the root cause of the infection.
Vaccine development is another active area, with candidates designed to prevent initial infection (prophylactic vaccines) or to reduce outbreaks and transmission in already infected individuals (therapeutic vaccines). Moderna is developing mRNA-1608, a therapeutic mRNA vaccine candidate specifically for HSV-2, which also shows potential for cross-protection against HSV-1. This candidate is currently in a fully enrolled Phase 1/2 clinical trial involving participants with recurrent genital herpes. BioNTech is also developing a prophylactic mRNA HSV vaccine candidate, BNT163, which is in Phase 1 development. Conversely, GSK’s therapeutic vaccine candidate, GSK3943104, recently completed a Phase 1/2 trial but did not meet its primary efficacy objective and will not progress to Phase 3.
Beyond vaccines and gene therapy, new antiviral approaches are also under investigation. Pritelivir is a novel helicase-primase inhibitor that works differently from existing antivirals. It is active against both HSV-1 and HSV-2, including strains that have become resistant to current medications. Pritelivir is currently undergoing a Phase 3 clinical trial for the treatment of acyclovir-resistant mucocutaneous HSV infections in immunocompromised patients and has received FDA Breakthrough Therapy Designation. Additionally, Theralase Technologies is exploring Ruvidar, a topical treatment that demonstrated complete healing of HSV-1 lesions in preclinical mouse studies. Ruvidar, which does not require light activation, showed superior effectiveness to acyclovir in destroying HSV-1 and preventing its replication in these studies.
What to Expect from Future Research
While the research landscape for herpes treatments is dynamic and promising, it is important to manage expectations regarding timelines. Much of the groundbreaking work, such as the gene therapy approaches, is still in preclinical stages, primarily tested in animal models. Even promising vaccine candidates and novel antivirals are in early to mid-stage clinical trials.
The journey from initial research to a widely available, FDA-approved therapy or cure typically spans many years. As of now, there is no FDA-approved cure or broadly accessible preventative vaccine for herpes. Despite these challenges, the ongoing research reflects a significant global commitment to addressing the public health impact of herpes. The National Institutes of Health (NIH) has outlined a strategic plan for HSV research, emphasizing the importance of improving understanding, diagnosis, treatment, and prevention of the virus. These concerted efforts offer hope for more effective solutions in the future.