What are Herpes Simplex Virus (Hsv) Vaccines?
HSV-1 is mainly transmitted by oral-to-oral contact to cause oral herpes (cold sores), while HSV-2 is usually transmitted through sexual contact and causes genital herpes. Both viruses establish life-long infection in humans after the initial infection. They periodically reactivate from sites in the nervous system to cause recurring sores or lesions at the original site of infection or other sites.
HSV-1 is highly contagious and widespread globally. According to the World Health Organization (WHO), over 3.7 billion people under age 50 (67%) have HSV-1 infection. HSV-2 is also widespread. The WHO estimates that around 417 million people aged 15-49 years worldwide have genital herpes infection due to HSV-2.
Existing challenges in Herpes Simplex Virus (Hsv) Vaccines
Despite the high global prevalence and lack of a cure, Herpes Simplex Virus (Hsv) Vaccines there is currently no approved vaccine for herpes viruses. Developing an effective vaccine is challenging due to the ability of the viruses to establish lifelong latent infections and periodically reactivate from neuronal sites. Another challenge is the partially protective host immune response following natural infection. During latency, the virus employs immune evasion strategies and remains invisible to the immune system.
Existing candidate vaccine approaches
Scientists have tried various approaches to develop effective vaccines against HSV infections:
- Subunit vaccines containing glycoprotein components of the viral envelope have shown some success in animal trials but failed to protect against infection or disease in humans. Stronger immune responses may be needed.
- Live-attenuated viral vaccines with mutations disabling their ability to establish latency were safe and immunogenic in animals but have concerns about potential adverse effects in humans.
- DNA vaccines encoding viral proteins showed promise in preclinical studies but failed to protect against disease in human efficacy trials. Multiple immunizations may be needed to improve protection.
- Vectored vaccines utilizing viral vectors like adenoviruses to deliver HSV proteins have shown the ability to generate durable immune responses in animal models and are being tested in clinical trials.
Latest advancements in vaccine strategies
Recently, novel vaccination approaches are showing promising results against herpes viruses:
- A glycoprotein-inactivated vaccine developed by Genocea Biosciences induced antiviral antibodies and CD4+ T cell responses that significantly reduced genital HSV-2 shedding in a Phase 2 clinical trial. A Phase 3 trial is planned.
- RVX-411 from Rocket Pharmaceuticals combines HSV protein antigens with an adjuvant to boost cellular immunity. In a Phase 1 trial, it was well-tolerated and generated robust neutralizing antibody and T cell responses.
- A replication-defective HSV-2 vaccine candidate from Vical effectively inhibited genital and neural disease in guinea pig models. It is being evaluated in non-human primate models.
- A two-component cytomegalovirus (CMV) vaccine comprising adjuvanted protein antigens along with a viral vector booster produced durable, protective immunity in rhesus monkeys. Human trials are underway.
- Targeting conserved viral proteins that are essential for establishment and reactivation of latent infections may offer a universal approach against diverse herpesviruses.
Progress towards clinical disease endpoints
While past candidate vaccines generated immune responses in humans without preventing infections, the latest strategies increasingly demonstrate ability to protect against viral shedding and disease endpoints in animal models.
with further optimization of vaccine regimens and selection of candidates inducing robust, broad and durable immunity, clinical efficacy against symptomatic disease may be achievable in forthcoming human trials. Advancements against CMV also offer promise for a multiple vaccine approach covering clinically important herpesviruses. Continued research efforts hold promise to eventually deliver the first effective vaccines against these globally widespread pathogens.
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