Herpes Vaccine Myths vs. Facts: What You Need to Know

The Current State of Herpes Vaccine Development

Scientists have been working tirelessly for decades to develop a vaccine against HSV, but it has been a long and challenging journey . One of the main obstacles is the virus's unique ability to establish latency in the nervous system, essentially hiding from the immune system and making it difficult to target with a vaccine . Despite these challenges, research is ongoing, and there are several promising vaccine candidates currently in clinical trials .

In 2017, the World Health Organization (WHO) outlined a series of priorities for herpes vaccine development, emphasizing the need for vaccines that are safe, effective, and accessible to all populations . These priorities have guided research efforts and spurred renewed interest in finding a solution to this global health concern. In line with this renewed focus, the National Institute of Allergy and Infectious Diseases (NIAID) recently announced a Request for Information on vital strategic approaches to developing an HSV Strategic Plan . This initiative highlights the growing recognition of the need for a herpes vaccine and the commitment to investing in research to achieve this goal.

Current herpes vaccine candidates utilize a variety of approaches, including:

• mRNA vaccines: Moderna (mRNA-1608) and BioNTech (BNT163) are at the forefront of this effort, developing mRNA vaccines that encode HSV-2 glycoproteins to trigger a robust immune response . Interestingly, while these vaccines primarily target HSV-2, they may also offer some protection against HSV-1 infection .

• Live-attenuated vaccines: Rational Vaccines is developing a live-attenuated vaccine (RVx201) that uses a modified form of the ICP0 protein to reduce the virus's ability to cause disease . Live-attenuated vaccines have been successful in preventing other viral infections, and this approach holds promise for herpes as well.

• Gene editing technology: Shanghai BD Gene is exploring a cutting-edge approach using gene editing to deliver Cas9 mRNA via lentivirus . This innovative technology could potentially target and eliminate the latent herpes virus, offering a potential cure or long-term remission.

• Therapeutic vaccines: Redbiotec is focusing on a therapeutic vaccine designed to reduce the frequency and severity of outbreaks in individuals already infected with HSV-2 . This type of vaccine could significantly improve the quality of life for people living with herpes.

These ongoing clinical trials represent significant progress in the pursuit of a herpes vaccine. While no vaccine has yet been approved for use in humans, the research provides hope for a future where herpes can be effectively prevented or controlled.

Types of Herpes Viruses and Vaccine Targets

Herpesviruses are a large family of viruses that can cause a variety of infections in humans. There are eight types of human herpesviruses . The most well-known are HSV-1 and HSV-2, which cause oral and genital herpes, respectively. However, it's important to understand that HSV-1 and HSV-2 can both infect the mouth and genitals, though they tend to have different patterns of recurrence . HSV-1 is more commonly associated with oral herpes (cold sores), while HSV-2 is the primary cause of genital herpes. However, an increasing number of genital herpes cases are now caused by HSV-1 .

Other herpesviruses can cause conditions such as chickenpox (varicella-zoster virus), shingles (reactivation of varicella-zoster virus), mononucleosis (Epstein-Barr virus), and even certain cancers (Epstein-Barr virus and Kaposi's sarcoma-associated herpesvirus) . While current herpes vaccine development primarily focuses on HSV-1 and HSV-2, scientists are also investigating the potential for vaccines to target other herpesviruses . The success of the varicella vaccine in preventing chickenpox and the shingles vaccine in preventing shingles demonstrates the feasibility of developing effective vaccines against herpesviruses .

Interestingly, the differences in how HSV and VZV interact with the human body might explain why it has been more challenging to develop a vaccine for HSV . For example, HSV has a larger genome and encodes more proteins than VZV, some of which are involved in evading the immune system . These differences highlight the complexity of HSV and the need for continued research to understand its unique characteristics and develop effective vaccine strategies.

A Look Back: The History of Herpes Vaccine Development

The quest for a herpes vaccine has been a long and winding road, marked by both progress and setbacks. Early attempts to develop a herpes vaccine date back to the 1930s, but these efforts were largely unsuccessful . In the following decades, various vaccine approaches were explored, including inactivated vaccines, subunit vaccines, and live-attenuated vaccines, but none proved effective in human trials .

One notable example is the GEN-003 therapeutic vaccine, which was tested in a phase 1/2 clinical trial . This vaccine, consisting of HSV-2 antigens with an adjuvant, showed some promise in reducing viral shedding and lesion rates immediately after vaccination. However, the effects were not long-lasting, and further research is needed to optimize this approach .

Despite these past challenges, the pursuit of a herpes vaccine continues. Advances in vaccine technology, such as the development of mRNA vaccines and gene editing techniques, have opened up new possibilities for preventing and treating HSV infections. The lessons learned from previous trials, coupled with a renewed focus on herpes vaccine research, provide hope that an effective vaccine will eventually become a reality.

Debunking the Myths

Misinformation and misconceptions about herpes vaccines can create confusion and hesitancy. Let's address some of the most common myths:

Myth 1: A herpes vaccine already exists.

The truth is: While vaccines exist for other herpesviruses, such as varicella-zoster virus (which causes chickenpox and shingles), there is currently no FDA-approved vaccine for HSV-1 or HSV-2 . It's important to differentiate between these different types of herpesviruses and understand that a vaccine for one does not necessarily provide protection against the others.

Myth 2: Herpes vaccines are unsafe.

Actually: Clinical trials for herpes vaccines have generally shown a good safety profile. While some mild side effects, such as pain at the injection site, fatigue, or headache, have been reported in some trials, no significant safety concerns have been identified . As with any vaccine, potential side effects are carefully monitored, and rigorous testing is conducted to ensure safety and efficacy before approval for public use.

Myth 3: Herpes vaccines will cause herpes.

The reality is: Most herpes vaccine candidates in development do not use live viruses, so they cannot cause herpes . Even live-attenuated vaccines, like the one being developed by Rational Vaccines, are designed with modifications to minimize the risk of causing an active infection .

Myth 4: Herpes vaccines are unnecessary because herpes is not a serious health issue.

This is a misconception: While herpes is often stigmatized and associated with mild symptoms, it can have significant physical and psychological impacts on individuals. Genital herpes can cause painful sores, increase the risk of HIV transmission , and lead to complications during pregnancy, such as miscarriage or premature birth . Beyond the physical effects, herpes can also cause emotional distress, relationship problems, and social stigma. Furthermore, the economic burden of genital herpes is substantial, with lifetime direct medical expenditures estimated at $972 per treated case in the United States . The widespread prevalence of HSV and its potential impact on individuals and public health underscore the need for effective preventive measures, such as a vaccine.

Myth 5: Only promiscuous people get genital herpes.

Fact: Anyone who is sexually active can get genital herpes. It is a very common infection that can be transmitted through any type of sexual contact, even with just one partner. This myth perpetuates harmful stereotypes and contributes to the stigma surrounding herpes.

Myth 6: Condoms prevent genital herpes.

Fact: While condoms can reduce the risk of transmission, they do not offer complete protection against genital herpes. The virus can be spread through skin-to-skin contact, even in areas not covered by a condom.

Ongoing Clinical Trials and Resources

Several clinical trials are currently underway to evaluate the safety and efficacy of herpes vaccine candidates. Here are some notable examples:

• Moderna's mRNA-1608: This phase 1/2 trial is testing an mRNA vaccine for HSV-2 in adults with a history of recurrent genital herpes .

• BioNTech's BNT163: This phase 1 trial is evaluating an mRNA vaccine for the prevention of genital lesions caused by HSV-2 in healthy adults .

• Rational Vaccines' RVx201: This observational study is assessing a live-attenuated HSV-2 vaccine candidate in England .

• GEN-003: This phase 1/2 trial tested a therapeutic vaccine consisting of HSV-2 antigens with an adjuvant. While it showed some initial promise in reducing viral shedding and lesions, the effects were not long-lasting, and further research is needed .

These trials are crucial for determining the effectiveness of these vaccine candidates and paving the way for potential approval and widespread use.

For those interested in learning more about herpes vaccine clinical trials, the following resources provide valuable information:

• ClinicalTrials.gov: This website is a registry and results database of publicly and privately supported clinical studies conducted around the world.

• CenterWatch.com: This website provides information about clinical trials, including a trial finder tool and resources for patients and researchers.

• Herpes Cure Pipeline 2.0: This resource tracks preclinical and clinical study timelines and strategies for herpes vaccines and cures.

These resources can help you stay informed about the latest developments in herpes vaccine research and find clinical trials that may be relevant to you.

Potential Benefits and Risks of Herpes Vaccines

The potential benefits of herpes vaccines are substantial. They could:

Benefits

• Reduce the transmission of HSV: This could prevent new infections and potentially contribute to the eradication of the virus.

• Lower healthcare costs: A vaccine could reduce the economic burden associated with treating herpes infections and complications.

• Improve the quality of life for people with herpes: By reducing outbreaks and associated symptoms, a vaccine could alleviate pain, discomfort, and emotional distress for those living with HSV.

• Contribute to HIV prevention efforts: By preventing HSV-2 infections, a vaccine could indirectly reduce the risk of HIV acquisition and transmission, particularly in areas with high HIV prevalence .

Risks

While clinical trials have not identified any significant safety concerns associated with herpes vaccines, it's important to acknowledge that, as with any vaccine, there is always a possibility of mild side effects . These side effects may include:

• Pain or redness at the injection site

• Fatigue

• Headache

• Muscle aches

These side effects are typically mild and temporary. The potential benefits of a herpes vaccine are likely to far outweigh any minor risks.

Conclusion

The development of an effective herpes vaccine is a complex and ongoing process. While challenges remain, significant progress has been made in recent years, with several promising vaccine candidates in clinical trials. By understanding the facts and dispelling the myths surrounding herpes vaccines, individuals can make informed decisions about their health and contribute to the fight against this prevalent virus.

The future outlook for herpes vaccines is hopeful, but there are still hurdles to overcome. One major challenge is the lack of investment in herpes vaccine research, which has hindered the progress of clinical trials . However, the NIH's strategic plan for herpes research and the NIAID's request for information on strategic approaches signal a renewed commitment to advancing vaccine development .

Another promising development is the emergence of novel vaccine platforms, such as the one being developed by Thyreos, Inc., which could potentially protect against a range of herpesviruses . This innovative approach could revolutionize herpes prevention and treatment in the years to come.

While we await the availability of an approved herpes vaccine, it's crucial to continue practicing safe sex, utilize suppressive therapy when necessary, and stay informed about the latest research and clinical trials. With continued research, investment, and public awareness, a herpes vaccine will hopefully become a reality, offering a new era of prevention and treatment for this widespread infection.