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Herpes Vaccine Candidates

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March 5, 2024
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Herpes Vaccines 2024

Developing protective herpes simplex virus (HSV) vaccines has been an ongoing challenge for decades. HSV is highly adapted to evade host immunity, making it difficult for a vaccine to prevent the virus from reaching the ganglia, which is the site of latency. Various herpes vaccine candidates are based on DNA, modified mRNA, protein subunits, killed virus, and attenuated live virus vaccine technologies. In addition, the World Health Organization (WHO) published its preferred product characteristics for Alpha (α)-herpesviruses vaccines and updated its pipeline review. As of March 2024, the U.S. Food and Drug Administration (FDA), BrazilCanada, ChinaEurope, India, Japan, and the U.K. had not authorized preventive or therapeutic herpes vaccines. 

The U.S. Department of Health and Human Services (HHS) invited stakeholders on February 6, 2024, to provide written public comments on the draft HSV Addendum to the STI National Strategic Plan. The deadline for comment submission to HHS is February 16, 2024.

Herpes Vaccine Candidates

When developing herpes vaccines, candidates conduct clinical trials called phase 1, phase 2, phase 3, and phase 4. Each development phase is essential. The WHO, the U.S. National Instuties of Health (NIH), and global partners launched STI Watch, a portal containing updated information on vaccine development status. Both preventive and therapeutic HSV vaccines are being explored. This HerpesFolds table gives interactive access to all AlphaFold structures of HSV-1 strain 17 (Uniprot proteome UP000009294), HCMV strain Merlin (UP000000938), EBV strain B95-8 (UP000153037), as well as KSHV strain GK18 (UP000000942), visualized by 3Dmol.js. The AlphaFold includes two additional Herpesviruses: PrV (UP000154030) and MHV68 (UP000099649).

Current herpes vaccine candidates in clinical trials include:

Herpes Simplex Virus-targeted immunotherapy (HSVTI) is conducting a phase 1/2 clinical study of targeted immunotherapy (GSK3943104A) against HSV in healthy participants aged 18-40 years or in participants aged 18-60 years with recurrent genital herpes.

mRNA-1608 is an mRNA vaccine candidate against HSV-2 disease. The mRNA-1608-P101 phase 1 study launched on September 6, 2023, and is forecasted to be completed on June 4, 2025. With mRNA-1608, Moderna Inc. aims to induce a strong antibody response with neutralizing and effector functionality combined with cell-mediated immunity. Independent Study: An mRNA vaccine to prevent genital herpes. Moderna stated on September 13, 2023, that the latent and other vaccine market is estimated at approximately $10 billion to $25 billion.

BNT163 is an mRNA-based HSV vaccine candidate that encodes three HSV-2 glycoproteins to help prevent HSV cellular entry and spread and counteract HSV immunosuppressive properties of HSVs. Prof. Dr. Harvey M. Friedman, Professor of Infectious Diseases at the University of Pennsylvania Perelman School of Medicine, conducted preclinical and scientific research on HSV. In the phase 1 clinical trial, the first subject was dosed in December 2022, and the safety, tolerability, and immunogenicity of BNT163 were evaluated. The last study update was posted on January 5, 2023.

Rational Vaccines's VC2 vaccine candidate is a live-attenuated vaccine targeting facial, ocular, and genital herpes caused by HSV-1 and potentially protects against genital herpes caused by HSV-2. On October 13, 2023, Rational Vaccines was awarded $2.8 million by the U.S. National Institute of Health, and in a 2018 study conducted at Louisiana State University, Brent Stanfield and colleagues examined the immune response generated by intramuscular injection of the VC2 vaccine in the guinea pig.

Delta gD-2 (∆gD-2) is a vaccine candidate based on an HSV-2 virus genetically deleting glycoprotein D (gD-2)

HSV529 (HSV15) is a vaccine candidate classified as a replication-defective virus, meaning the virus possesses all the wild-type HSV virus components except two proteins, UL5 and UL29, involved in viral DNA replication. This phase 1/2 study was last updated on January 13, 2021, by Sanofi Pasteur and the National Institute of Allergy and Infectious Diseases.

EXD-12 is a vaccine candidate currently in preclinical testing for safety and efficacy as a prophylactic and therapeutic vaccine for herpes simplex virus 1 (HSV-1) and herpes simplex virus 2 (HSV-2). 

NanoVax is an adjuvant platform to develop a vaccine candidate to protect against the two viruses that can cause genital herpes.

RVx201 is a live-attenuated HSV-2 vaccine candidate conducting an observational clinical study RVx-001-PSS in England designed to have a specific degree of attenuation through specifically designed mutations in the ICP0 protein.

Shanghai BD Gene is conducting a phase 1/2 clinical study in humans. It is the only gene-editing technology for Cas9 mRNA delivery by lentivirus.

Assembly Biosciences, Inc. announced data from development candidate ABI-5366, a long-acting HSV helicase inhibitor targeting high-recurrence genital herpes.

Repurposed BCG Vaccination Targeting Herpes

The Bacillus Calmette-Guérin (BCG) vaccine is an approved attenuated vaccine for tuberculosis prevention. Research published by The Lancet in 2023 suggests that BCG vaccination induces three non-specific immune responses: trained immunity, heterologous immunity, and anti-inflammatory effects. These immune responses have been used to prevent and treat various diseases, including HSV-1. In the journal eClinicalMedicine, Laure F Pittet and colleagues published their phase 3 clinical trial results conducted across multiple countries to assess the impact of BCG vaccination on recurrent herpes labialis. The BRACE trial (NCT04327206) concluded that BCG-Denmark vaccination had a beneficial effect on herpes labialis, particularly in males with frequent recurrences. Still, it may increase the risk of a first cold sore.

systematic review of Medline, EMBASE, and PubMed was published in September 2020 that concluded BCG vaccination has a potential, safe, affordable, and readily available candidate intervention to decrease the high burden of disease associated with HSV infection and recurrences but adequately controlled randomized trials are required.

Herpes Vaccine Preclinical Development

Redbiotec is currently developing an HSV-2 therapeutic vaccine (immunotherapy). Their vaccine program is T-cell-mediated protection and aims to outperform antivirals and allow patients to stay symptom-free for >12 months with two injections.

Eurocine Vaccine vaccine candidates against HSV-2 - in a non-human study, mRNA vaccination stimulated potent T cell responses that significantly outcompeted those generated by the protein vaccine in performance in several specific areas. Dr. Karl Ljungberg, Director of Preclinical Development at Eurocine Vaccines, stated in December 2022, "The T cell responses that we report here align with those that can be detected after recovery from an infection and are focused on the part of the HSV-2 virus that we believe is important to target to obtain immunologic control of the virus."

Researchers designed and constructed an HSV-1 synthetic platform based on H129-G4. This platform could facilitate further manipulation of the HSV-1 genome for developing neuronal circuit tracers, oncolytic viruses, and vaccines.

The journal MDPI published an article on July 18, 2023, that concluded B7 costimulation molecules expressed from a replication-defective vaccine can enhance vaccine efficacy, even in an immunocompetent host.

Herpes Vaccine Clinical Trials

Sponsored clinical trials recruit prospective participants in various studies. Herpes Cure Advocacy launched Herpes Cure Pipeline 2.0 (March 2022), which tracks preclinical and clinical study timelines and strategies globally.

Herpes Testing

The JAMA Network published on February 14, 2023, that the U.S. Preventive Services Task Force recommends against routine serologic screening for genital HSV infection in asymptomatic adolescents and adults, including pregnant women, as neonatal herpes infection is uncommon. (D recommendation).

Herpes Treatments

Herpes treatments are available in 2024. However, these products do not cure herpes.

HSV-2 Preventive Gel Clinical Development

Researchers announced in September 2022 that they had developed a gel-based lubricant that can potentially prevent individuals from being exposed to HSV-2. Cow mucus provides the basis for a synthetic prophylactic gel developed at the KTH Royal Institute of Technology to protect against herpes transmission. Advanced Science published this Research Article on September 14, 2022. The researchers synthesized BSM gels that liquefied under large strain and self-healed rapidly and repeatedly after the strain was removed. They showed that these properties were essential for mucin lubrication, as evidenced by significantly improved lubrication by the mucin gels (5%, wt/v) compared to mucin solutions (5%, wt/v). They also showed that the gels inhibited the infection of HSV-2 in epithelial cells and immune cells by about 80%.

Hongji Yan, a biomaterials researcher at KTH, commented in a media statement the promising results raise hope that when it becomes available as a product, the gel could help reverse troubling trends in the spread of sexually transmitted infections. 

Genital Herpes Serologic Screening

The U.S. Preventive Services Task Force (USPSTF) recommends against routine serologic screening for genital herpes simplex virus infection in asymptomatic adolescents and adults, including pregnant women. As of August 16, 2022, recommendations made by the USPSTF are independent of the U.S. government. 

Because of the poor performance, a high rate of false-positive test results of commercially available U.S. FDA-approved HSV tests, and the limited availability of confirmatory testing, prevention efforts for herpes transmission have been insufficient. The CDC's Office of Science issued a Broad Agency Announcement in December 2022 for the competitive selection of research proposals, including an RFP for serologic tests for HSV, reported Herpes Cure Advocacy,

Sexually Transmitted Disease Vaccines

As of 2024, Sexually Transmitted Disease vaccine news is posted at Precision Vaccinations.

Herpes Vaccine News

February 12, 2024 - Researchers at Dartmouth's Geisel School of Medicine and Thayer School of Engineering published a new study in Cell Reports Medicine, offering insights into how antibodies function in combating HSV infections. 

December 14, 2023 - Harvard News - New study (Oct. 26, 2023) findings could inform the design of treatments for various viruses that replicate in the cell nucleus.

November 1, 2023 - The University of Pittsburg School of Medicine received a grant of $504 thousand to conduct innovative herpes research.

October 13, 2023 - Rational Vaccines was awarded $2.8 million in U.S. National Institute of Health funding in three separate grants to further its research to diagnose, treat, and prevent the spread of HSV.

September 30, 2023 - A Systematic Review was published: The Association Between Herpes Simplex Virus and Alzheimer's Disease.

May 25, 2023 - Akiko Iwasaki, Ph.D., Sterling Professor of Immunobiology and professor of dermatology, molecular, cellular & developmental biology, and epidemiology (microbial diseases) at Yale School of Medicine, developed a therapeutic vaccine candidate that may reduce the reactivation of genital herpes in guinea pigs. However, lack of investment has hindered human clinical trials.

April 21, 2023 - The NIAID announced a Request for Information on the U.S. National Institutes of Health's vital strategic approaches to developing an HSV Strategic Plan.

April 5, 2023 - The WHO published updated Herpes Facts, including an HSV-2 infection increases the risk of acquiring HIV.

March 20, 2023 - Research Article: Construction and characterization of a synthesized herpes simplex virus H129-Syn-G2.

December 21, 2022 -  BioNTech S.E. announced that the initial subject was dosed in a first-in-human Phase 1 clinical study of BNT163, an HSV prevention vaccine candidate.

December 20, 2022 - Eurocine Vaccines announced the mRNA vaccine generates superior T-cell responses. Dr. Karl Ljungberg, Director of Preclinical Development at Eurocine Vaccines, stated, "The T cell responses that we report here are in line with those that can be detected after recovery from an infection and are focused to a part of the HSV-2 virus that we believe is important to target to obtain immunologic control of the virus."

December 15, 2022 - A study published by the peer-reviewed journal PLOS Medicine conducted if HSV-2 has indeed contributed to the transmission of HIV, then nearly one-third of antiretroviral costs and HIV-related wage losses add to herpes-related costs. Given the magnitude of the combined losses, a vaccine against HSV-2 must be a global priority.

December 12, 2022 - The Lancet Europe published a systematic review, meta-analyses, and meta-regressions on the epidemiology of HSV-2 in Europe.

December 9, 2022 - The journal Nature published an article: Urgency and necessity of Epstein-Barr virus (EBV) prophylactic vaccine development. EBV is a γ-herpesvirus that contains a double-stranded DNA genome and is the first identified human oncogenic virus. The EBV, also known as human herpesvirus 4, is a member of the herpes virus family, says the U.S. CDC.

October 27, 2022 - Contagion (Vol. 07, No. 5) - Revisiting Old Foes: Updates on HSV.

October 22, 2022 - The JAMA Network published an Original INvestigation - Viral Shedding 1 Year Following First-Episode Genital HSV-1 Infection - that concluded genital HSV-1 shedding declined rapidly following an initial infection and during the first year.

October 6, 2022 - Wiley Online published a case report on herpetic endotheliitis and stromal keratitis following inactivated COVID-19 vaccination. This is the first report of herpetic endotheliitis and stromal keratitis following the BBIBP vaccine. Although the temporal link between vaccination and adverse ocular events, including HSV-1 reactivation, cannot be established through these case reports, these reports add to the sparse body of evidence supporting this notion. 

September 26, 2022 - The Fred Hutchinson Cancer Center in Washington announced researchers (Drs. Keith Jerome and Martine Aubert) found substantial reductions in oral and genital viral shedding in the treated mice, with many of those treated showing no detectable virus shed. A related non-peer-reviewed study was also published: AAV-delivered gene editing for latent genital or orofacial herpes simplex virus infection reduces ganglionic viral load and minimizes subsequent viral shedding in mice.

September 23, 2022 - Nature - Scientific Reports published: HSV-1 0∆NLS vaccine elicits a robust B lymphocyte response and preserves vision without recognizing t HSV-1 glycoprotein M or thymidine kinaon. Collectively, the results suggest (1) the live-attenuated HSV-1 mutant 0∆NLS elicits a robust B cell response that drives select B cell responses more significantly than the parental HSV-1 and (2) HSV-1 TK and gM are likely expendable components in the efficacy of a humoral response to ocular HSV-1 infection.

September 19, 2022 - Virios Therapeutics, Inc. announced topline results from its Fibromyalgia Outcome Research Trial Evaluating Synergistic Suppression of HSV-1 study of oral IMC-1 for the treatment of F.M. "We believe the interplay between different COVID-19 strains and herpes virus activation may be contributing to the differential response we observed in patients enrolled in 2021 versus 2022," stated Greg Duncan, Chairman and CEO of Virios Therapeutics.

August 19, 2022 - The journal Neurology published a RESEARCH ARTICLE: Herpes Viruses: Associations With Brain Volumes, Cognitive Performance, and Plasma Biomarkers. Discussion. These findings suggest an association of symptomatic herpes virus infection with white matter volume loss, attentional decline, and astrogliosis.

August 15, 2022 - Rational Vaccines announced the launch of an observational clinical study of RVx201 in the U.K. on August 3, 2022, that will recruit about 200 participants. In addition to assessing the typical baseline characteristics of the population, the purpose of this study is also to determine the acceptance of clinical trial procedures and understand the interest of the target patient population to participate in a therapeutic Phase 1/2 HSV-2 vaccine study.

July 8, 2022 - Rational Vaccines announced findings from a U.S. NIH-funded pilot study of RVX201 that showed that it reduced recurrent genital lesions compared to the gD2-alum/MPL vaccine or placebo in vivo. In addition, RVX201 appears to generate a robust cellular immune response equivalent to that elicited by wild-type HSV-2 on Day 7 post-infection.

June 16, 2022 - Eurosurveillance reported researchers in Austria had identified a second strain of extensively drug-resistant gonorrhea. 'We describe the second global XDR N. gonorrhoeae strain, with high-level resistance to azithromycin and resistance to ceftriaxone, cefixime, cefotaxime, ciprofloxacin, and tetracycline, which caused a possible gonorrhea treatment failure with ceftriaxone (1 g) plus azithromycin (1.5 g).

June 14, 2022 - Eurocine Vaccines AB announced that it entered into a research and collaboration agreement with Redbiotec AG that transfers the exclusive global rights to develop, manufacture, and commercialize vaccine candidates against Herpes Simplex Virus Type 2, HSV-2, based on the technologies developed by Redbiotec.

June 1, 2022 - Virios Therapeutics, Inc. announced the results of a pilot study performed at the University of Alabama, titled "Gastric Herpes Simplex Virus Type 1 Infection is Associated with Functional Gastrointestinal Disorders in the Presence and Absence of Comorbid Fibromyalgia: A Pilot Case-Control Study", were published in the journal Infection in April 2022. These results provide evidence for a potential mechanistic connection between active herpes virus infection and functional gastrointestinal Disorders ("FGID"), with or without comorbid fibromyalgia ("F.M."), as well as the potential for combination antiviral therapy to treat patients with FGIDs and F.M.

May 11, 2022 - Peer-review study: The health impact of seven herpesviruses on (pre)diabetes incidence and HbA1c: results from the KORA cohort. Conclusion: HSV2 and CMV serostatus associations with (pre)diabetes incidence indicate that these herpesviruses may contribute to impaired glucose metabolism.

April 25, 2022 - Frontiers Immunology published: Combinatorial Herpes Simplex Vaccine Strategies: From Bedside to Bench and Back. 'We discussed that a prime/pull vaccine strategy using asymptomatic epitopes, combined with immune checkpoint blockade, would be a successful herpes vaccine approach.'

January 25, 2022 - PNAS published a study that developed a parameterized model predicting how much and how rapidly a betaherpesvirus-vectored transmissible vaccine can be expected to reduce the prevalence of a target pathogen. The study concluded, 'Our models are focused on transmissible vaccines designed using herpes virus vectors and demonstrate that these vaccines—currently under development for several important human pathogens—may have the potential to control zoonotic pathogens within the reservoir hosts rapidly. However, our study results suggest that the effectiveness of MCMV-vectored transmissible vaccines may depend on the virus strain used to construct the vaccine and the target population into which the vaccine is ultimately deployed.'

November 22, 2018 - Study: The live attenuated prophylactic HSV vaccine, VC2, was effective in the guinea pig model of genital HSV-2. Its decreased ability to infect neural tissues provides advantages over live attenuated vaccines. The live attenuated prophylactic HSV vaccine, VC2, was effective in the guinea pig model of genital HSV-2. Its decreased ability to infect neural tissues provides advantages over live attenuated vaccines.

January 9, 2014 - Review: The challenge of developing herpes simplex virus 2 vaccines.

Content sources include the WHO, US CDC, NIH, research papers, ClinicalTrials.gov, and the Precision Vaccinations news network. Healthcare providers, such as Dr. Robert Carlson, fact-check content.

Clinical Trials

No clinical trials found