The Centers for Disease Control and Prevention (CDC), the Office of Science (OS) in late December 2022 issued a Broad Agency Announcement (BAA) for the competitive selection of research proposals, including a Request for Proposal (RFP) for a new serologic test for herpes simplex virus (HSV).
Therefore, the goal of the RFP is to develop, validate, and make accessible confirmatory (2nd step) HSV serologic assays for diagnosis, especially for HSV-2, to improve the specificity of the testing algorithm. Offering such testing widely will increase equitable access for all persons in need of confirmatory testing.
Because of poor performance of commercially available FDA-approved tests, and limited availability of confirmatory (2nd step) testing, prevention efforts for transmission of herpes have been insufficient. Herpes spreads without public health intervention primarily by asymptomatic carriers, emphasizing the critical and unmet need for accurate diagnosis and testing. With this announcement, the CDC indicates their support for accurate testing and diagnosis, and further advances the prevention of HSV transmission as a national priority.
Learn more about advocacy for herpes cure, treatment and prevention here.
Sexual health advocates have long called on the CDC, FDA and federal agencies to address the silent epidemic of herpes by urgently prioritizing cure, treatment and prevention. Providers and patients have been asked to report the poorly performing tests to the FDA. There are 572,000 confirmed cases of genital herpes a year in the US, according to a 2018 report. Prevalence of oral herpes is unknown but estimated to be 50% of Americans.
Project objectives include:
CDC seeks projects to develop type-specific serologic assays for confirmation of HSV diagnosis, especially for HSV-2, that improves the specificity of the serology testing algorithm overall.
Develop technology and user interface for specimen submission with high accessibility to various healthcare providers and linkage to commercial submitter laboratories for processing and reporting.
Learn more about the CDC request for proposals and apply here.
Hyundai Biosciences have applied for a clinical study in Korea to test the efficacy of CP-COVO3, a new candidate treatment for viral infections, on HPV.
This antiviral agent, developed in Korea, has an innovative ‘viral removal’ mechanism applicable to all viruses, unlike existing antiviral agents that target only specific viruses. It is expected to open a new chapter in the world’s antiviral drug history if it produces valid clinical results.
This new clinical trial is not for HSV specifically, but its mechanism of action should apply to HSV as well if it works for other pathogens. Niclosamide, the active ingredient in CP-COV03, has been proven to treat HSV in infected cells (clinical data is pending publication) via a novel delivery mechanism. Niclosamide has been used as a medication for various diseases for over 60 years and has a strong safety profile.
Hyundai Biosciences previously has successfully completed phase II clinical trials for treating COVID and monkeypox, and applied for fast-track approval and distribution in May 2022. They have also started setting up manufacturing sites in the U.S. They’re now starting studies on other diseases.
The research team has said, “Niclosamide is a substance that has already been taken as an insect repellent for more than 60 years, and its safety has been sufficiently verified. As it has an effective antiviral function, I thought that it has sufficient potential for HPV treatment for which antiviral drugs have not yet been developed.”
December 21 2022, BioNTech announced they had dosed the first clinical trial participant. This is the first-in-human study aims to evaluate the safety and immunogenicity of prophylactic herpes virus vaccine candidate BNT163.
Company statement; “We aim to help address diseases with a high unmet medical need and of global health relevance, and we are combining our new technologies such as #mRNA and our expertise in immune engineering. As part of our strategy, we have announced that the first subject was dosed in a first-in-human Phase 1 clinical trial with BNT163, a prophylactic herpes simplex virus-2 vaccine candidate. The program is part of our collaboration with the University of Pennsylvania.”
Trials are active and currently recruiting for health volunteers without HSV infection.
Locations are currently open in North Carolina, with more locations to be added.
Apply to participate in clinical trial for herpes vaccine
Join Dr. TJ Cradick, Chief Scientific Officer at Excision Biotherapeutics to learn about Excision Bio pre-clinical work in gene therapy for Herpes Simplex. Excision is developing CRISPR-based therapies to cure viral infectious diseases and improve the lives of chronically ill patients. A recognized expert in genome editing technologies, Dr. Cradick has developed nucleases, as well as genome editing and gene therapy reagents and methods for CRISPR/Cas nuclease, TAL Effector Nucleases (TALENs) and Zinc Finger Nucleases (ZFNs), both in his academic work at University of Iowa and the Georgia Institute of Technology, and in-industry at Sangamo Therapeutics (NASDAQ: SGMO).
Professor, Vaccine and Infectious Disease Division
Dr. Keith Jerome is a renowned virologist whose research focuses on viruses such as herpes simplex, HIV and hepatitis B that persist in their hosts. He studies the ways in which these viruses evade the immune system and potential therapies for these infections. Dr. Jerome and The Jerome Lab are currently in pre-clinical development with a gene therapy to cure latent HSV.
Betsy C. Herold, M.D.: Harold and Muriel Block Chair, Dept. of Pediatrics
March 22nd 6pm EST
Professor and Vice Chair for Research, Department of Pediatrics and Microbiology-Immunology. Chief, Division of Pediatric Infectious Diseases
Albert Einstein College of Medicine
Betsy Herold, M.D. directs a basic and translational research program, which focuses on the prevention of HIV and HSV and other viral infections. Basic research in the lab focuses on the development of a novel vaccine candidate that protects against HSV-1 and HSV-2 in multiple rigorous small animal models by eliciting antibodies that provide sterilizing protection through antibody-dependent killing. The lab is also developing monoclonal antibodies to treat and prevent HSV. The vaccine is being advanced to the clinic by X-vax Technology.
Terri Warren has served as principal investigator or sub-investigator on more than 120 clinical trials evaluating various testing mechanisms for sexually transmitted infections, the efficacy of experimental vaccines, and pharmacologic interventions for numerous human infections. Her area of special expertise is the herpes simplex virus.
Join for a discussion with Herpes Cure Advocacy medical advisory board member Dr. Gary Richwald. Learn about the latest advances in herpes simplex virus cure, treatment and prevention efforts in the US and globally, how to advocate for change, the role of the patient advocate and more.
Testing for herpes is complicated and can be confusing in America.
Currently available, FDA-approved IgG antibody tests sometimes present with false positive results where the test says you are infected with HSV and you are not. Tests can also have false negative results. Most often, false positive results are found in the index value range of 1.1 to 5.0 but IgG false positives can be as high as 17.
As a result, CDC guidelines call for TWO STEP testing to confirm a herpes diagnosis. Meaning once the initial IgG antibody test is performed, a follow-up confirmatory test is recommended. This two-step process has been recommended per the CDC guidelines because currently available diagnostic IgG antibody tests are so often false negative/positive.
Availability of the confirmatory test (the second step test) is limited and many providers do not know how to take steps to order the confirmatory testing for patients.
To access confirmatory testing and confirm a herpes diagnosis – patients will need to order the Western Blot (WB) from the University of Washington. The WB test is not FDA-approved, needs to be ordered directly from UW, and a blood sample sent directly to their academic lab for processing.
The UW Western Blot is widely considered the gold standard for herpes antibody testing. While the initial IgG test looks for a single antibody protein to distinguish and identify HSV-1 and HSV-2, the WB looks for all of the proteins associated with herpes antibody. This makes the Western Blot test a much more comprehensive look for evidence of HSV infection. There is no such thing as a false positive WB.
Patients and professionals wanting to order Western Blot directly from Univ. Washington, can do so by taking the following steps:
Order Herpes Testing with University of Washington Western Blot
How do I confirm a herpes diagnosis? Read how here.
STEP 1: CALL TO ORDER: 1-800-713-5198or1- 206-685-6066.
The package contains blood draw and transport tubes, lab instructions, lab requisition form, labels for the outside of the packaging, address to ship back to the University of Washington. The kit comes in an anonymous brown cardboard box and says nothing about the sender (Univ. Washington) or it’s contents on the packaging.
STEP 2: BLOOD DRAW: Drawing of blood for testing.
The patient (and/or healthcare professional needs to identify a location to draw and process their blood sample. The location chosen must include a centrifuge to spin down the blood sample to separate the red cells from the clear serum.
NOTE: LabCorp and Quest WILL NOT draw blood to ship for testing to Univ. of Washington. They currently do not offer any confirmatory testing for Herpes.
Below is a list of labs to go to for a blood draw.
ARCpoint laboratories: They will also draw blood for a feeand you can enter your zip code in their website for a lab location near you.
YOUR LOCAL HOSPITAL OUT PATIENT LAB: A hospital lab may be able to draw blood using the WB kit. Check with your local hospital lab or your own health care provider!
STEP 3: A physician or health care provider fills out a form for University of Washington.
Patients need to identify a health care provider to fill out a form and order this test. The required lab requisition form will be included in the UW kit. Patients who need a health care provider can work with your own physician.
To confirm your herpes diagnosis from an HSV expert, contact Westover Heights Clinic for support with this process from anywhere in the United States.
STEP 4: Ship blood sample, completed form and a check for payment to University of Washington.
Patients will need to purchase a pre-paid shipping label from UPS or FedEx to ship the sample to UW.
The laboratory that draws your blood can usually ship it the kit after they have processed your sample.
STEP 5: Your provider will contact you with your results!
Results usually take 1-2 weeks, and sometimes longer. The possible results are positive, negative or indeterminate. There are no numbers associated with these results.
Herpes Diagnosis: Learn more about University of Washington Western Blot
Additional guidance from University of Washington to order a Western Blot is available here.
We lost our baby to neonatal herpes, and her life mattered. Our daughter would be turning a year old this coming September 2022. Instead of celebrating her birth, though, we will be gathering to memorialize her 27 days of life. Our daughter died a horrible death due to acquiring HSV-2 in the birth canal, also known as Neonatal Herpes.
As I write this, the guilt and anger that I must reckon with each day fills my chest with unbearable grief knowing that she died because of me. However, by telling our story it is my intention that some of my guilt and anger be used to create justice and change in the standards of care for women as well as infants. What happened to our baby is inexcusable because it was avoidable. If I had known my status, the proper steps would have been taken to ensure that our first and only child entered this world safely and in good health.
I am 37 years old and had to go through IVF to create the embryo that would later develop into our beautiful daughter. I think back on all of the blood tests, invasive ultrasounds, vaginal examinations, and wonder how something like this could get past all of those screenings. I am fortunate in that I had access to the best doctors and medical care available and attended every appointment in addition to monthly ultrasounds due to my “geriatric” age. My pregnancy was wonderful. It was easy and I loved having 38 weeks to imagine what this creature would be like and who she would become. If you are a parent, you know that the imagining of who your baby is and what life will be like with them is a large part of the waiting and preparing for their arrival. When your baby is born, so are all your hopes and dreams for them.
Our daughter was delivered vaginally and without an epidural. I, like many mothers, had meticulously planned how I wanted delivery to go and I was determined to stick with it. My point in including these details is because I was doing everything I could to avoid a C-section. Statistically, if you are medicated and are in labor for longer than is convenient, doctors can push a cesarian. There’s less liability and it saves time. The ironic thing about my birth plan is that it was planned to avoid the very thing that might have saved our daughter – having a C-Section.
Had HSV been included on the extensive list of other STI’s and STD’s that women are tested for during initial OB appointments, it is very likely that I would have known that I was a carrier. I say likely because there is a high false positive rate for HSV serology tests along with a high rate of positive asymptomatic carriers. As of today, contemporary medical practice depends upon its patients having physical and/or visual symptoms to determine whether to test for HSV or not. I have never had any symptoms or anything that would have prompted me to seek medical attention and/or ask to be tested. Instead, I found out that I was HSV-2 positive through the death of my daughter. I would never know otherwise.
Medical protocols aside, I had never even heard of Neonatal Herpes. I’m an educated woman, read every baby book, went to every medical appointment required in the many months of prenatal care. Not one single baby book or pamphlet out of all the baby books and other educational literature that I read to prepare for our daughter mentioned a risk of neonatal herpes. Not one. My doctors never mentioned neonatal herpes. It is detestable that not only did it take my daughter’s life to learn that I carried this deadly virus but that it was a risk to be aware of to begin with. WHY? Why aren’t we preventing this when we have tests to help? We should be doing more, It is unjustifiable that I, along with other mothers both knowing and not of their status, am having to ask this.
WHY? Why aren’t we preventing this when we have tests to help? We should be doing more, It is unjustifiable that I, along with other mothers both knowing and not of their status, am having to ask this.
After three torturous and grueling days in the Pediatric Intensive Care Unit where our daughter was kept alive through life support, the doctors gave us our daughters’ diagnosis. Neonatal Herpes. They told us that statistically a baby dying from herpes is comparable to being struck by lightning twice in one lifetime and yet it happened to us. It is remarkable how quickly a statistic becomes personal when you are a part of the data. Suddenly something that was once so far away from your life’s orbit falls into existence with the force of a meteorite hitting planet earth. It’s explosive.
Our daughter’s diagnosis was not made known to us until 30 hours after she was admitted to the PICU for seizures. She had exhibited symptoms prior to the seizures but none that deviated enough from the norm to raise alarm. Typical symptoms of Neonatal Herpes are lethargy, slow weight gain, rapid breathing or difficulty breathing, jaundice, blisters on skin, and irritability. If you have had a newborn, you can see just how easy it is to mistake one thing for another. In our case, our daughter exhibited slow weight gain and in retrospect, lethargy. However, we were taking her to the pediatrician every other day to be weighed and examined and therefore assumed everything was okay. The doctor wasn’t alarmed so neither were we. Slowly she began to gain weight and aside from being a challenge to wake up for feedings, she presented as a typical newborn.
It was around day 25 that I began to suspect something was not right. Several times while holding her to calm her from fussing, she would tense her entire body and turn a scarlet red. Her cry changed to a lower vocal range. It was alarming but our baby nurse said it was gas and it truly did look like that. Now knowing that the virus attacks the brain first, I can only assume that she was experiencing a pain that no adult could endure. This is what haunts me most.
The day after a second episode of the body tensing and unusual but temporary change in skin pigment, she developed raspy breathing. When we brought her to the pediatrician, she examined our daughters’ eyes and immediately told us to take her to the ER and not to stop for any reason. This would be the last time I held my daughter, free from tubes and monitors and tears. A day and a half later, my husband and I, along with my parents held her as she took her last breaths.
Writing our story, our daughter’s story, for others to read is an act of courage and I am doing it for her. There is no justice that will right the loss of her life—of any life. Herpes virus is deadly and yet it has been allowed to spread and kill and ruin lives despite our knowledge of this. I do not understand how a virus that is so common has been allowed to continue to be consciously omitted from standardized STI/STD testing and, at the very least, from OB and pediatric education. I happen to be one of the “lucky” asymptomatic carriers but I will forever grieve the precious life of my child.
TAKE ACTION TO HELP PREVENT NEONATAL HERPES
Herpes Cure Advocacy has launched a new Neonatal Herpes Task Force to provide support for families, engage with stakeholders, physicians, and scientists, and create change to protect Americans from neonatal herpes.
Herpes Cure Advocacy celebrates and thanks the US House of Representatives for their prioritization of federal action for Herpes Simplex Virus cure, treatment and prevention in the FY 2023 House budget report.
In the house budget report for FY 2023, published on June 29, there is report language that directs NIH to assemble a multi-council working group of NIH staff to investigate the NIH clinical research HSV treatment, cure and prevention, and provide recommendations to address the infectious disease which impacts 1 out of 2 Americans.
This direction for NIH gives multiple institutes the opportunity to work together to address the gaps and opportunities in HSV cure, treatment, and prevention in a coordinated effort that leverages medical knowledge across institutes. Also, congress has directed NIH to issue a funding analysis that outlines NIH-funded clinical research for HSV. Report language is included on page 146 and also below.
Please note, that before this FY 2023 budget is passed into law, it still needs to have support on the senate side.
Herpes Cure Advocacy: CALL TO ACTION
It is more important than ever for advocates for herpes cure, treatment and prevention to write to their elected representatives in the US Senate and ask them to support the increased federal funding for HSV for FY 2023.
Herpes Simplex Virus, Types 1 and 2.—The Committee recognizes the serious nature of herpes simplex virus, a neuropathic infectious disease which impacts nearly one in two Americans, and the critical need for Federal investment in treatment and prevention.
The Committee is concerned with potential health, quality of life, and economic impacts for herpes simplex virus seropositive individuals, as well as the risk for severe, persistent disease in a significant portion of Americans. The Committee directs NIH to prioritize research and development of curative approaches to herpes simplex virus, with a specific focus on research projects with commercial viability and intention of bringing new HSV treatments to market.
The Committee understands that herpes simplex virus is a pathogen with considerations beyond a single NIH Institute or Center and directs NIH to assemble a multi-council working group to ensure a coordinated and focused effort across NIH. Institutes and Centers may include, but are not limited to: NIAID, NIMH, NCI, NIA, NIMHD and NINDS. This working group will assemble a review of NIH efforts in herpes simplex virus treatment and prevention with commercial viability, outline gaps and/or misconceptions in currently available research, and outline future priority areas for new clinical research, with a focus on addressing Americans holistic health and well-being. The multi-council working group will also provide a funding analysis to illustrate NIH priorities, gaps, and opportunities in clinical research of HSV treatment to date.
Chinese company BDGene from Shanghai continues to lead in the global race for a herpes keratitis cure. The highly anticipated treatment, BD111 has reached a big milestone as it applied for Orphan Drug designation from the US FDA. Previously, BD111 has received international attention for its progress with a gene editing cure for herpes keratitis. We reported on its progress – which it has published in the top international academic journals Nature Biotechnology and Nature Biomedical Engineering.
BD Gene has (in collaboration with the Eye and ENT Hospital of Fudan University) carried out 3 cases of IIT human clinical trials, and has reported pre-clinical results where study subjects were cleared of the virus. The potential to change the landscape for Herpes treatment has patient advocates very excited.
Orphan drugs, also known as rare disease drugs, refer to drugs used for the prevention, treatment and diagnosis of rare diseases. The orphan drug designation granted by the FDA applies to drugs and biologics for rare diseases that affect less than 200,000 people in the United States each year, and provides policy support for related products. Therefore, obtaining orphan drug designation is of great advantage for manufacturers bringing new medicines to market.
Possible herpes cure takes another important step
According to the U.S. FDA Orphan Drug Act, new drugs that have obtained orphan drug qualification allows for a series of advantages for BDGene including quicker, easier processes to get to market in the US. Supports include tax credit for clinical research expenses, Exemption of NDA/BLA application fees, access to special R&D funds, special approval channels, exemption from the declaration of some clinical data, and a seven-year market exclusivity period after the drug is approved. Orphan Drug Designation can also bring investment as the company continues to lead the market.
About Herpes Keratitis: Herpes virus keratitis is caused by herpes simplex virus (HSV-1) infection and is the most common infectious blindness disease. Current first-line antiviral drugs can only inhibit viral replication by interfering with viral DNA synthesis. These drugs can inhibit HSV-1 DNA replication, but cannot clear the latent viral genome in the cornea and trigeminal ganglion, which leads to the disease. Repeated attacks can lead to blindness in severe cases.
About BD111: CRISPR-based gene editing technology can directly degrade the viral genome, providing the possibility of fundamentally curing the disease. BD111 gene editing drugs get rid of the drawbacks of traditional related drugs that need to be repeatedly administered, and only need to be injected once. The drug uses the original delivery technology of VLP to transduce the CRISPR gene editing tool to directly target and cut the HSV-1 genome, so as to achieve the purpose of removing the HSV-1 virus genome, thereby realizing the treatment of herpes virus keratitis. The characteristics of the BD111 drug are: (1) Cas9 mRNA is delivered, and the gene enzyme stays in the body for a short time, which can reduce the risk of immune response and gene editing off-target; (2) It cuts the viral genome and does not need to change anyone’s genes, not detected to off-target effects on the human genome.
The BioNTech team and UPenn have previously partnered on pre-clinical study of an mRNA-based vaccine candidate to prevent genital herpes. This work is led by lead investigator Dr. Harvey Friedman and team at the University of Pennsylvania.
A new clinical trialA Clinical Trial in Healthy Volunteers to Study the Safety, Tolerability, and Immune Responses After Vaccination With an Investigational Vaccine Designed to Prevent Genital Herpes Lesions is now testing the BioNTech/UPenn formulation, BNT163, and it is recruiting as of today.
The clinical trial, posted on ClinicalTrials.gov on June 27th, is enrolling HSV negative individuals to test the effectiveness of a vaccine candidate to prevent genital herpes. Trials are set to begin in September 2022 with a completion date of 2025. Locations for the study are to be determined and will be posted when finalized.
This clinical trial is for HSV negative, healthy participants to test safety and efficacy in a two-part study. Part A will be multiple doses of vaccine, The highest dose that is well tolerated will be studied in a larger number of subjects in part B.
Regarding a therapeutic to treat those living with genital herpes: Within the next 1-2 months, Dr. Friedman and his lab will be turning energies towards a therapeutic, plans for an experimental approach are underway.
GSK has officially updated its clinical research pipeline to include a vaccine for HSV-2! Their therapeutic vaccine for HSV-2 isn’t mRNA (or what they called SAM technology) but an adjuvanted therapeutic vaccine.
The trial (currently recruiting) is a Phase 1/2 combined trial that ends in 2024. GSK will test 9 different formulations as a prophylactic, the one that has the highest efficacy will then be tested in Part 2 as a therapeutic. Ultimately, advocates assume, that GSK will make one vaccine as both a prophylactic/therapeutic.
GSK Formulation: GSK3943104A: Therapeutic HSV (Immunomodulator): Active Immunization to suppress recurrence of genital herpes in adults aged 18 years and older.
GSK is the manufacturer of Shingrix (shingles vaccine released in 2017) and is perfectly positioned to leverage their knowledge from this very effective vaccine for another herpes virus for a new formulation to treat Herpes Simplex. Shingrix is also a recombinant protein adjuvanted vaccine with 90-97% efficacy over 7 years with one 2-dose regimen.
GSK has a proven platform for developing a highly effective recombinant protein – adjuvanted herpes vaccine. They are now simply tweaking it slightly for a new target in HSV-2. HSV and VZV (VZV = Varicella-zoster virus the virus that causes chickenpox and shingles) are both alpha herpes viruses. They are genetically very closely related, are latent viruses that live in the body for life, and when reactivated exhibit symptoms in the body similarly. Both herpes simplex and zoster are viruses that hide in the nerve ganglia and reactivate on the skin in the same manner with blisters, prodrome, etc.
Advocates are excited that GSK is taking this approach and hopeful that as one of the largest pharma companies globally, and entering clinical studies for herpes simplex for the second time, they’re confident about the safety and efficacy of this formulation. The new formulation is estimated to reduce viral shedding to the extent that the infection would be non-transmissible to partners or what is known as a functional cure.
For other projects in the Herpes Cure Pipeline, see here.
For more details on the new GSK clinical trial for Herpes and to apply to participate please visit here.