Herpes Simplex Virus Type 1 (HSV-1) is a widespread infection. While often associated with mild symptoms, managing outbreaks and preventing transmission poses challenges. Its potential complications underscore the need for an effective vaccine. Such a vaccine could significantly alter the landscape of this common infection.
Understanding HSV-1
Herpes Simplex Virus Type 1 is highly prevalent globally, affecting a significant portion of the population, including an estimated 57-80% of adults in the United States. It commonly manifests as oral herpes, or cold sores, typically appearing around the mouth. The virus spreads primarily through direct contact with infected secretions or skin-to-skin contact.
Most HSV-1 infections are mild or asymptomatic, though symptomatic cases cause discomfort and social stigma due to visible lesions. In some instances, HSV-1 can lead to more serious complications, including ocular herpes, which can impair vision, or, rarely, encephalitis, a brain inflammation. HSV-1 establishes lifelong latency within nerve cells, periodically reactivating and causing recurrent outbreaks, contributing to its persistent burden.
The Quest for an HSV-1 Vaccine
Developing an effective HSV-1 vaccine presents challenges due to its sophisticated biology. One primary challenge stems from HSV-1’s ability to establish latency, hiding dormant within nerve cells, evading immune eradication. This latency allows for periodic reactivation and recurrent outbreaks, even after antibodies develop. The virus also possesses mechanisms to suppress or evade immune responses, complicating vaccine design.
Researchers are exploring several vaccine strategies. Subunit vaccines use specific viral parts, like glycoprotein D (gD), to stimulate an immune response without introducing the whole virus. This approach aims to induce protective antibodies that can neutralize the virus.
Live-attenuated vaccines use a weakened virus that can replicate but not cause disease, mimicking natural infection to elicit robust immunity. Nucleic acid-based vaccines (mRNA or DNA) instruct human cells to produce viral proteins, prompting an immune response. Each strategy aims to induce strong, long-lasting immunity to prevent infection or reduce outbreak severity and frequency.
Current Status of Vaccine Research
HSV-1 vaccine development is an active research area, with several candidates progressing through clinical trials. One notable candidate is the investigational gD-2 subunit vaccine, targeting HSV-2 glycoprotein D, which has shown cross-protective efficacy against HSV-1 genital disease. A Phase 3 trial of this gD-2 subunit vaccine showed 58% efficacy against HSV-1 genital disease in women without prior HSV-1 or HSV-2 antibodies, but no efficacy against HSV-1 oral herpes.
Another promising approach involves live-attenuated vaccines, such as the VC2 candidate from Rational Vaccines. This vaccine targets facial, ocular, and genital herpes caused by HSV-1, and may protect against HSV-2. This live-attenuated HSV-1 mutant, 0ΔNLS, has shown significant protection against ocular HSV-1 in preclinical studies, demonstrating a robust neutralizing antibody response and reduced nervous system infection.
Moderna is also developing an mRNA-based vaccine, mRNA-1608, aiming to induce strong antibody and cell-mediated immune responses against both HSV-1 and HSV-2. This candidate is currently in a Phase 1 study, expected to complete in June 2025.
Other candidates include EXD-12, tested as both a prophylactic and therapeutic vaccine against HSV-1 and HSV-2, currently in Phase 1/2 studies. GSK plc also completed a Phase 1/2 study for its therapeutic HSV vaccine candidate, GSK3943104, in September 2024. While it did not meet its primary efficacy objective for recurrent genital herpes, no safety concerns were observed.
Potential Impact of a Vaccine
An effective HSV-1 vaccine could bring significant public health benefits. Such a vaccine would likely reduce oral herpes outbreaks (cold sores), decreasing associated discomfort and social stigma. Beyond these immediate effects, a vaccine could also lower the risk of more severe, albeit rarer, complications such as ocular herpes (potentially impairing vision) and herpes encephalitis, a serious brain infection.
A vaccine could play a substantial role in reducing virus transmission, leading to a decline in new infections. Individuals would experience an improved quality of life due to fewer or no recurrent outbreaks, alleviating physical and psychological distress. This reduction in disease burden could also translate into decreased healthcare costs, offering individual and societal advantages.