Herpes Vaccines 2024
Developing protective herpes simplex virus (HSV) vaccines has been an ongoing clinical trial challenge for decades. Current herpes vaccine candidates are based on DNA, modified mRNA, protein subunits, killed virus, and attenuated live virus vaccine technologies. The World Health Organization (WHO) published its preferred product characteristics for Alpha (α)-herpesviruses vaccines and updated its pipeline review in 2024. As of November 18, 2024, the U.S. Food and Drug Administration (FDA), Brazil, Canada, China, Europe, India, Japan, and the U.K. had not authorized preventive or therapeutic herpes HSV-1 or HSV-2 vaccines.
Herpes Vaccine Candidates
As of November 2024, herpes vaccine candidates conducting clinical trials include:
Assembly Biosciences ABI-5366 is an advanced helicase primase inhibitor targeting Healthy Participants and Participants Seropositive for HSV-2 With Recurrent Genital Herpes. The phase 1a/1b clinical trial (NCT06385327, ABI-5366-101) found that ABI-5366 was well tolerated and presented a pharmacological profile supporting potential once-weekly or even once-monthly dosages.
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. These glycoproteins help prevent HSV cellular entry and spread and counteract HSV immunosuppressive properties.
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. This means the virus possesses all the wild-type HSV virus components except two proteins, UL5 and UL29, involved in viral DNA replication. Sanofi Pasteur and the National Institute of Allergy and Infectious Diseases last updated this phase 1/2 study on January 13, 2021.
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. It is 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.
A research study published on May 28, 2024, highlights the potential of effective combination therapy with two monoclonal anti-gB IgGs (HDIT101 and HDIT102) for treating HSV-1 and 2 conditions.
GSK plc announced on September 11, 2024, that it had completed the primary objective data analysis from the phase II part of the TH HSV REC-003 trial for GSK3943104, a therapeutic HSV vaccine candidate. Results show that GSK3943104 did not meet the study's primary efficacy objective. This vaccine candidate, therefore, will not progress to phase III studies.
Herpes Vaccine Candidate Clinical Trials
When developing herpes vaccines, participants are selected for clinical trials segmented by phase 1, phase 2, phase 3, and phase 4. Each development phase is essential. Herpes Cure Advocacy launched Herpes Cure Pipeline 2.0 (March 2022), which tracks preclinical and clinical study timelines and strategies.
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.
HSV-1 is a neurotropic virus and the cause of herpes simplex encephalitis. 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).
The Vaccine Value Profile (VVP) for HSV is intended to provide a high-level, holistic assessment of the information and data that are currently available to inform the potential public health, economic, and societal value of pipeline vaccines and vaccine-like products.
HSV vaccines are primarily needed by women and pregnant women to prevent ulcers and neonatal herpes infections. Women comprise up to 65% of infections in the United States and worldwide.
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 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.
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.
Sexually Transmitted Disease Vaccines
As of 2024, Sexually Transmitted Disease vaccine news is posted at Precision Vaccinations.
Herpes Vaccine News
September 11, 2024 - GSK plc provided update on phase I/II therapeutic HSV vaccine trial, which has been terminated.
July 24, 2024 - An article published in Nature: TMEFF1 is a neuron-specific restriction factor for HSV.
May 13, 2024 - Fred Hutch virologists Martine Aubert, PhD, and Keith Jerome, MD, PhD, are conducting laboratory experiments to develop a gene therapy for curing herpes.
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 - The findings of a new study (October 26, 2023) 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 that 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 on the 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 titled "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. EBV is also known as human herpesvirus 4, a member of the herpes virus family.
September 26, 2022—The Fred Hutchinson Cancer Center in Washington announced that 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.
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.
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.
