Herpes

Characteristics of Patients Diagnosed With Recurrent Symptomatic Genital Herpetic Disease

Massachusetts-based Rational Vaccines Inc. today announced the launch of an observational clinical trial designed to determine the baseline characteristics of patients diagnosed with recurrent symptomatic herpes simplex virus type 2 (HSV-2).

In addition to assessing the typical baseline characteristics of a 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 in humans.

The RVx-001-PSS vaccine candidate study, "A Study of the Characteristics of Patients Diagnosed With Recurrent Symptomatic Genital Herpetic Disease," is being conducted at Southampton University Hospital and Chelsea and Westminster Hospital London, England.

The study was launched on August 3, 2022, and intends to recruit about 200 adults.

"Patients who develop symptomatic herpetic disease suffer not only from recurrent physical symptoms but may also suffer from social stigma and isolation because the infection is usually transmitted sexually," commented Kerstin Westritschnig, M.D., chief medical officer of Rational Vaccines, in a related press release on August 15. 2022.

"There is no cure for herpes.... and there are no approved vaccines, immunotherapies, or sufficiently reliable diagnostics currently available."

"Antiviral medications developed in the 1970s can help to reduce the severity and frequency of symptoms but cannot cure the infection."

"We look forward to initiating this clinical study as these findings will help inform the design of our Phase 1/2 clinical trial, which will evaluate our lead vaccine candidate for HSV-2," added Dr. Westritschnig.

According to a 2020 report by the World Health Organization, herpes infects billions globally.

Herpes simplex virus (HSV), commonly referred to as herpes, is categorized into two types: herpes simplex virus type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2).

HSV-1 is the primary cause of oral herpes but can also cause genital herpes, and HSV-2 is the primary cause of genital herpes.

In addition to the RVx201 vaccine candidate, several other vaccines are conducting clinical studies.

For example, Moderna Inc. announced earlier this year that the mRNA-1608 vaccine candidate targets HSV-2 disease.

mRNA-1608 aims to induce a strong antibody response with neutralizing and effector functionality combined with cell-mediated immunity.

As of today, the U.S. FDA has not approved any herpes vaccine. Additional herpes vaccine development news is posted at PrecisionVaccinations.com/Herpes.

PrecisionVaccinations publishes fact-checked, research-based vaccine news curated for mobile readership.

Sub Title:

Rational Vaccines RVx-001-PSS study will include 200 participants

References:

Rational Vaccines

Herpes vaccine candidates

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Tuesday, August 16, 2022 - 05:15

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Herpes Simplex Virus and Neurodegenerative Diseases Linkage Identified

Don Hackett — Thu, 14 Oct 2021 18:37:05 +0000

Reviewer:

UIC researchers find evidence of possible link between herpes simplex and neurodegenerative diseases

A new study by researchers at the University of Illinois Chicago (UIC) suggests that when the protein optineurin (OPTN) is present in cells it restricts the spread of herpes simplex virus type 1 (HSV-1).

This study shows that OPTN selectively targets HSV-1 tegument protein, VP16, and the fusion glycoprotein, gB, to degradation by autophagy.

OPTN deficiency unveils severe consequences for recruitment of adaptive immunity and suppression of neuronal necroptosis.

Furthermore, Ocular HSV-1 infection is lethal without OPTN and is rescued using a necroptosis inhibitor.

In a “first of its kind” study published recently in the journal Nature Communications, researchers also found a potential direct connection between neurodegenerative diseases, such as Alzheimer’s disease, amyotrophic lateral sclerosis (ALS), glaucoma, and the herpesvirus.

Led by Dr. Deepak Shukla, the Marion H. Schenk Esq. Professor in Ophthalmology for Research of the Aging Eye, and vice chair for research at UIC, these researchers sought to discover why HSV-1 can become fatal for individuals who are immunocompromised but not for healthy individuals.

Herpesviruses naturally infect the central nervous system and can result in degenerative brain and eye disorders, as well as encephalitis.

However, in most individuals, the virus is suppressed during a primary infection before it can significantly damage the central nervous system.

The new research suggests why HSV-1 is suppressed.

OPTN, a conserved autophagy receptor, selectively targets HSV-1 proteins to degradation by autophagy, explained Tejabhiram Yadavalli, a co-author of the study and visiting scholar at UIC’s department of ophthalmology and visual science.

“OPTN stops the virus from growing and it stops it by autophagy — engulfing the virus particles inside tiny vesicles called autophagosomes. The autophagy that happens is very selective. That has meaning for other viruses as well,” Dr. Shukla said in a related press release

The researchers believe the results from this study will apply to eight different human herpesviruses.

For the study, mice with removed OPTN genes were infected with ocular HSV-1. The virus growth was much higher in the brains of animals without OPTN, killing local neurons and eventually leading to animal death.

This shows there is a faster degeneration of neurons when OPTN is not there.

Additional studies are being planned to examine naturally occurring mutations in OPTN, such as the ones reported in glaucoma and ALS patients, and how they may affect neuronal health and HSV-1 infection, Shukla explained.

“Where you have mutated OPTN plus herpes, you have the recipe to create a disaster in terms of neurodegeneration,” Shukla said.

“The study also shows there is an impairment of immune response when there is a deficiency in OPTN. OPTN is needed to signal an influx of proper immune cells at the site of infection. When you don’t have it, you have issues,” added Chandrashekhar Patil, also a co-author of the study and a visiting scholar at UIC’s department of ophthalmology and visual science.

Some of those issues could include neurodegenerative disorders, which researchers believe further research may show.

“We think we will have data to show other viruses, such as Epstein-Barr, Kaposi’s sarcoma, varicella-zoster, are all going to share this mechanism because they share homologous proteins,” Shukla said.

Because the herpes virus sits in neurons forever, there is speculation it is connected to neurodegenerative diseases.

The immune system requires inflammation to fight off the virus constantly, and neurons have some degree of damage because of this continuous immune response, according to Dr. Tibor Valyi-Nagy, professor of pathology, director of neuropathology at UIC, and research collaborator on the study.

The study also showed that animals without OPTN and infected with HSV-1 after 30 days lost the ability to recognize objects.

Shukla said this could be an indication that having HSV-1 along with a mutation of OPTN could accelerate neuronal damage, which would translate into cognitive impairment.

“Part of our translational research can be how can we correct the problems with OPTN so that we don’t have issues with neurodegeneration,” Shukla said.

These results place OPTN at the crux of neuronal survival from potentially lethal CNS viral infections.

Additional authors are Joshua Ames, Rahul Suryawanshi, James Hopkins, Alexander Agelidis, Chandrashekhar Patil, and Brian Fredericks, all of UIC, and Henry Tseng of Duke University Medical Center. No industry conflicts were disclosed.

This research was supported by the National Institutes of Health and National Eye Institute grants and the Butner Pioneer Award, Duke Health Scholars, and Research to Prevent Blindness unrestricted funds.

As of October 13, 2021, the U.S. FDA has not Approved a herpes vaccine. Vaccine candidates are listed on this webpage.

PrecisionVaccinations publishes fact-checked research-based vaccine news.

Sub Title:

Defects in protein optineurin functions compounded by HSV-1 infection have the potential to cause accelerated neuronal damage

References:

OPTN is a host intrinsic restriction factor against neuroinvasive HSV-1 infection

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Friday, October 15, 2021 - 06:15

Can mRNA Vaccines Defeat Herpes?

Don Hackett — Thu, 29 Apr 2021 19:41:11 +0000

Reviewer:

REcording of Harvey's Meeting

A research team at the University of Pennsylvania (UPenn) has been working on preventing and treating genital herpes (HSV-2) for years and recently found success with an mRNA vaccine approach, even before the COVID-19 pandemic.

The goals of a HSV-2 vaccine are to keep the herpes virus dormant. Or if the virus escapes, prevent it from causing symptoms.

Professor Harvey M. Friedman demonstrated success in animal models in July 2020. This study found not only targeting entry molecules, but also targeting the HS-2 ability to evade the immune system.

And, in collaboration with UPenn professor Drew Weissman, M.D., Ph.D., they are producing an mRNA vaccine. Dr. Weissman is an inventor of the COVID-19 mRNA vaccine approach, recently authorized by the U.S. Centers for Disease Control and Prevention (CDC).

The CDC stated during March 2021, mRNA vaccines teach human cells how to make a protein, or even just a piece of a protein, that triggers an immune response inside our bodies.

The benefit of mRNA vaccines, like all vaccines, is those vaccinated gain protection without ever having to risk the severe consequences of getting sick.

In the past, HSV-2 prevention vaccine clinical studies (Chiron 1999, GSK 2002 & 2012) targeted the molecules that the herpes virus needed to enter cells using a protein vaccine. These showed some benefits but did not meet the trial designs’ primary endpoints of preventing genital disease.

In the herpes animal models of mice and guinea pigs, the antibody response was found three times greater, and the CD4 T-cells were ten times better with the mRNA vaccine than the protein vaccine.

This superior molecular response was consistent with symptom reduction - the mRNA vaccine was perfect in preventing genital disease (100%) and significantly reduced recurrent disease (98%).

The duration and strength of the mRNA vaccine candidate protection were also better compared to a protein vaccine.

Studying guinea pigs over eight months, equivalent to 20 years in humans, the antibody response was 10x better with the mRNA vaccine after their vaccination. The mRNA vaccine reduced days with the genital disease to <1%, compared to 20% with the protein vaccine.

The risk of transmission (measured by days) was 2% with the protein vaccine, compared to 0% with the mRNA vaccine.

Dr. Friedman says a therapeutic vaccine needs to stimulate CD8 T-cells as opposed to CD4 T-cells.

On February 12, 2021, Dr. Friedman offered his insights in a free video hosted by Blue Jeans.

Dr. Friedman is ready to launch a herpes mRNA vaccine phase 1 human trial in early 2022. He and UPenn have established a donation page to accelerate the funding for this research. The donation page can be found on this webpage.

PrecisionVaccinations publishes research-based vaccine news.

Sub Title:

UPenn HSV2 vaccine candidate embraces mRNA technology

References:

Harvey M. Friedman, MD

An HSV-2 nucleoside-modified mRNA genital herpes vaccine containing glycoproteins gC, gD, and gE protects mice against HSV-1 gen

New Penn-Developed Vaccine Prevents Herpes in Mice, Guinea Pigs

Vaccines to prevent genital herpes

CDC: mRNA Vaccines

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Thursday, April 29, 2021 - 13:15

What Causes Sudden Herpes Virus Outbreaks?

Don Hackett — Sat, 13 Feb 2021 16:34:33 +0000

Reviewer:

Neuronal hyperexcitability is a DLK-dependent trigger of herpes simplex virus reactivation that can be induced by IL-1

University of Virginia (UVA) researchers have offered new insights on what causes herpes simplex virus (HSV-1) to flare up, explaining how stress, illness, and even sunburn can trigger unwanted outbreaks.

These researchers identified HSV-1 co-opts an innate immune pathway resulting from IL-1 stimulation of neurons to induce reactivation.

The discovery could lead to new ways to prevent cold sores and recurrent herpes-related eye disease from reoccurring, the researchers reported on February 11, 2021

“Herpes simplex recurrence has long been associated with stress, fever, and sunburn,” said researcher Anna R. Cliffe, of UVA’s Department of Microbiology, Immunology, and Cancer Biology, in a press statement.

Once infected with HSV, the virus never really goes away. Instead, it lurks inside neurons, waiting for the right moment to strike again, a process known as reactivation, added Dr. Cliffe.

Cliffe and her collaborators found that when neurons harboring the virus were exposed to stimuli that induce “neuronal hyperexcitation,” the virus senses this particular change and seizes its opportunity to reactivate.

In response to prolonged periods of inflammation or stress, the immune system releases a particular cytokine, Interleukin 1 beta.

This cytokine is also present in epithelial cells in the skin and eye and is released when these cells are damaged by ultraviolet light.

Interleukin 1 beta then increases the excitability in the affected neurons, setting the HSV stage to flare up, the UVA researchers discovered.

“It is remarkable that the virus has hijacked this pathway that is part of our body’s immune response,” Cliffe said. “It highlights how some viruses have evolved to take advantage of what should be part of our infection-fighting machinery.”

These UVA researchers demonstrate HSV-1 reactivation from latently infected mouse neurons induced by forskolin requires neuronal excitation. Stimuli that directly cause neurons to become hyperexcitable also induced HSV-1 reactivation.

Forskolin-induced reactivation was dependent on the neuronal pathway of DLK/JNK activation. It included an initial wave of viral gene expression independent of histone demethylase activity and linked to histone phosphorylation.

IL-1β is released under conditions of stress, fever, and UV exposure of the epidermis, all known triggers of clinical HSV reactivation.

They found that IL-1β induced histone phosphorylation and increased sympathetic neurons’ excitation. Importantly, IL-1β triggered HSV-1 reactivation, which was dependent on DLK and neuronal excitability.

The scientists say that more research is needed to fully understand the potential factors which play into herpes simplex disease. It may vary depending on the virus strain or the type of neuron infected.

“A better understanding of what causes HSV to reactivate in response to a stimulus is needed to develop novel therapeutics,” Cliffe said. “Ultimately, what we hope to do is target the latent virus itself and make it unresponsive to stimuli such as Interleukin 1 beta.”

Herpes simplex virus-1 (HSV-1) is one of the most common human pathogens present in approximately 40–90% of the population worldwide. Cold sores, also known as fever blisters, are among the most common symptoms of HSV reactivation.

HSV-1 is mainly transmitted by oral-to-oral contact to cause oral herpes and cause genital herpes. Herpes infections are most contagious when symptoms are present but can still be transmitted to others in the absence of symptoms, says the World Health Organization.

However, recurrent reactivation can lead to herpes keratitis - a severe eye disease which, if left untreated, can result in blindness. In extreme cases the virus can cause encephalitis.

The development of protective HSV vaccines has been an ongoing challenge for decades. Many vaccine candidates are under development, including DNA, modified mRNA, protein subunit, killed virus, and attenuated live virus vaccines.

Early-stage clinical trials to test therapeutic (intended to reduce viral shedding in people who are already infected with HSV) and preventive (designed to prevent infection) vaccine candidates are ongoing.

The researchers have published their findings in the scientific journal eLife. The research team consisted of Sean R. Cuddy, Austin R. Schinlever, Sara Dochnal, Philip V. Seegren, Jon Suzich, Parijat Kundu, Taylor K. Downs, Mina Farah, Bimal N. Desai, Chris Boutell, and Cliffe.

The work was supported by the National Institutes of Health’s National Institute of Neurological Disorder and Stroke, grant R01NS105630; the National Institute of Allergy and Infectious Diseases, and others.

No industry conflicts of interest were disclosed.

PrecisionVaccinations publishes research-based herpes virus vaccine news.

Sub Title:

Neuronal hyperexcitability is a DLK-dependent trigger of HSV-1 reactivation

References:

WHO: Herpes simplex virus

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Live-Attenuated Virus Vaccine Development 'is the Right Approach'

Don Hackett — Wed, 09 Dec 2020 15:57:08 +0000

Reviewer:

Rational Vaccines believes live-attenuated virus vaccine development is the right approach

A vaccine biotech firm based in Massachusetts points to the proven science of live-attenuated viruses in vaccine development as key to the company's commitment to the development platform.

A live-attenuated virus is a weakened (attenuated) virus that is able to multiply within the host to a limited extent and engineered to be unable to cause any disease.

In the past, scientists did not have the advanced molecular tools available today that allow for the rational attenuation of viruses. In addition, advances in whole genome sequencing have allowed for detailed genetic identification and manipulation of pathogens, thus enabling the rational design of safe and effective live-attenuated mutants.

"The live-attenuated vaccine approach has led to some of the most successful and cost-effective disease interventions in worldwide medical history," said Rational Vaccines’s CEO Agustin Fernandez, in a press statement issued on December 8, 2020.

“Rational attenuation of live viruses can produce very safe vaccines with practically no chance to cause disease.”

As an example, smallpox, polio, measles, rubella, chickenpox, and rotavirus vaccines are all live-attenuated.

Mass immunizations of the live-attenuated smallpox vaccine led to that disease being eradicated around the world in 1980. In 1961, the FDA approved a live-attenuated polio vaccine, ultimately leading to a 99% global reduction in polio by 2000 – the same year that measles was declared eradicated until vaccination gaps led to outbreaks beginning in 2017.

The first live-attenuated rubella (German measles) vaccine was introduced in 1961, with the U.S. declaring the country free of that disease by 2004.

More recently, the live-attenuated chickenpox vaccine accounted for dramatically reduced death rates and hospitalizations associated with that disease compared to before the vaccine's approved use in 1995.

And in 2006, the first attenuated live viral vaccines for rotaviruses were introduced, drastically reducing associated illnesses and hospitalizations in the U.S. and infant and child morbidity and mortality worldwide.

Concerns about the use of live-attenuated vaccines to compromised or underdeveloped immune systems led to the development of subunit vaccines. Subunit vaccines typically composed of one or more proteins of the targeted pathogen could be easily produced.

The hope was that when mixed with adjuvants that are prone to elicit strong immune responses against the pathogen, subunit vaccines could then produce adequate immune responses.

"Despite their benefits and safety, however, subunit vaccines frequently have limitations, especially against more complex pathogens and specifically latent viruses that remain in a 'silent' state within infected hosts.”

“For example, mutant viruses may escape anti-protein targeted immune responses, and may not induce long-term memory immune responses that protect against infection over a long period of time. Also, the possibility exists that weak antibody responses may enhance susceptibility to infection instead of preventing it, as is the case with Dengue viral infections," added, Dr. Konstantin Kousoulas, RvX Chief Scientific Consultant for Basic Sciences.

Rational Vaccines develops rationally engineered, live-attenuated viral immunotherapeutic and prophylactic vaccine candidates, particularly focused on combating all diseases resulting from herpes simplex virus 1 (HSV-1) and herpes simplex virus 2 (HSV-2) infections.

PrecisionVaccinations publishes research-based news.

Sub Title:

Rational Vaccines live-attenuated vaccines enable viruses to multiply within the host but engineered to not cause disease

References:

Understanding modern-day vaccines: what you need to know

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Can a 100 Year Old Vaccine Prevent Herpes Infections?

Don Hackett — Mon, 30 Nov 2020 19:59:22 +0000

Reviewer:

Does bacillus Calmette‐Guérin vaccine prevent herpes simplex virus recurrences? A systematic review

Recurrent infections with herpes simplex virus (HSV) in the orofacial, ocular, or genital region are common and sometimes disabling, calling for effective preventive interventions, said researchers in a recent review published by the Wiley Online Library.

The development of HSV protective vaccines has been an ongoing challenge for decades and continues today.

In this systematic review of Medline, EMBASE, and PubMed studies published on September 24, 2020, and there were 16 articles deemed relevant comprising both animal and human studies (301 patients) regarding the use of the Bacillus Calmette‐Guérin (BCG) vaccine’s off‐target effects that might impact the recurrence of HSV infections.

The BCG vaccine is an attenuated, live culture preparation of the Bacillus of Calmette and Guerin (BCG) strain of Mycobacterium Bovis. This 100-year-old BCG vaccine is targeted against tuberculosis, with protective non-specific effects against other respiratory tract infections.

In non-randomized human studies (that failed to control for a placebo effect), BCG vaccination appeared beneficial in 78 percent of adults with recurrent herpes genitalis or labialis, with 37 percent being recurrence‐free for an extended period, 41 percent experiencing less frequent or severe episodes, and only 22 percent reported no change.

This clinical benefit is consistent with the findings of immunological sub‐studies. In the two studies restricted to recurrent herpes labialis, 94 percent appeared to benefit from BCG.

In animals, BCG administration led to a 1.9 to 5.5‐fold increase in survival rate following HSV challenge (vaginal, corneal, or intraperitoneal inoculation).

This beneficial effect in animals was influenced by the dose of BCG (higher better), mode of administration (intradermal better than intraperitoneal), and the interval between vaccination and viral challenge (at least 6-days required).

In conclusion, these researchers stated, ‘ the BCG vaccine is a potential, safe, affordable vaccine candidate, however, it is very limited in availability.'

However, ‘properly controlled randomized trials are required in the future.’

Research funding for this study was from Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, Grant/Award Number: Early Postdoc.Mobility grant number P2GEP3_178155. No industry conflicts were disclosed.

Genital herpes is a common, sexually transmitted disease that any sexually active person can get. Most people with the virus don’t have symptoms. Even without signs of the disease, herpes can still be spread to sex partners.

More than 15 percent of people aged 14 to 49 years have genital herpes.

‘There is no cure for herpes, but medication is available to reduce symptoms and make it less likely that you will spread herpes to a sex partner,’ says the US Centers for Disease Control and Prevention (CDC).

A leading vaccine candidate in a clinical study is HSV529, which is classified as a replication-defective virus. 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 November 27, 2020, by Sanofi Pasteur.

PrecisionVaccinations publishes research-based vaccine development news.

Sub Title:

Bacillus Calmette‐Guérin (BCG) vaccine’s off‐target effects might impact the recurrence of HSV infections

References:

CDC: Genital Herpes

Bacille Calmette-Guerin (BCG) Vaccine

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Curing Herpes Comes Into Focus

Don Hackett — Wed, 19 Aug 2020 11:37:08 +0000

Reviewer:

Gene editing and elimination of latent herpes simplex virus in vivo

Fred Hutchinson Cancer Research Center researchers have been exploring the idea that lifelong infections with herpes viruses might be cured by using the DNA-cutting tools of gene therapy.

The initial research showed these techniques could knock out small quantities of latent virus, and the work of improving the study's results fell to virologists Dr. Keith Jerome Jerome and Dr. Martine Aubert.

This team has just published a paper in Nature Communications on August 18, 2020, showing that, through a series of incremental improvements on their original method, they had destroyed up to 95 percent of herpes virus lurking in certain nerve clusters of mice. Much of the team’s meticulous work of the past 5-years has involved finding better ways to target infected clusters of nerve cells and to thwart the virus’s ability to quickly repair the cuts to its genes.

“This is the first time that anybody has been able to go in and actually eliminate most herpes in a body,” said Dr. Jerome, who is also spearheading research at Fred Hutchinson.

“It is a completely different approach to herpes therapy than anybody’s ever had before. I hope that this study changes the dialogue around herpes research and opens up the idea that we can start thinking about a cure, rather than just control of the virus,’ commented Dr. Jerome in a press statement.

The hidden herpes viruses are disabled by an injection that tracks down infected nerve cells and induces them to make special gene-cutting enzymes, which work like molecular scissors, to slash viral genes in specific places.

Whereas most research on herpes has focused on suppressing the recurrence of painful symptoms, the Fred Hutch gene therapy work addresses the root cause of reactivation: the presence of the latent virus in infected nerve cells.

It will still take a long time before these mice experiments lead to human clinical trials to cure herpes. Dr. Jerome estimates that will be at least three years away.

The Jerome Lab’s herpes research thus far involves only HSV-1, but the scientists are now working on ways to extend their success to HSV-2. The first step will be to repeat their experiments using HSV-2 in guinea pigs, which, unlike mice, experience natural reactivations of herpes virus infections, just as humans do.

The advances in herpes cure research over the past five years are largely due to a series of improvements in the gene-editing tools. First, the researchers added combinations of different gene-cutting enzymes. The more cuts these molecular scissors make, the harder it is for the virus to recover.

Second, they chose different strains of harmless carrier viruses that do a better job of transporting those cutting tools to the places in the body where infected nerve cells are clustered.

“It’s been three or four years of work, but I think what we describe in the paper is a really big step,” said Dr. Aubert. “It gets us closer to really considering this as a curative approach. It gives us the green light.”

Since the earliest days of the experiments, the Jerome team learned to rely on a cutting enzyme called a “meganuclease” that can zero in on a segment of herpes DNA and cut both strands of the double helix. Despite the “mega” in its name, these scissors are extraordinarily small — about half the size of an antibody, those tiny, Y-shaped proteins our immune system uses to swarm over and disable viruses and bacteria.

The team attained its first promising results years ago using a single type of meganuclease that proved effective in cutting the herpes virus DNA, but the results were short-lived. The virus could rely on the infected cells’ own DNA-repair programs — which don’t distinguish between viral genes from their own — to fix the break most of the time.

But over time, the researchers found that they could eliminate up to 90% of the latent virus by using a mix of two or three different meganucleases. It is simply harder to repair two breaks than one. With more tinkering, the results continued to improve.

The researchers also refined their methods of transporting molecular scissors to targeted nerve cells. From the beginning, Jerome and his team have relied on a harmless, hollowed-out virus that is drawn to the surface proteins of nerve cells.

Called an adeno-associated virus vector, or AAV, it is the little workhorse of gene therapy. In this case, it is used to ferry to the infected nerve cells' genetic instructions that cause them to make those meganucleases.

“We inject the AAV vector, and it finds its way,” Aubert said.

Latent herpes viruses lurk in clusters of nerve cells called ganglia, and researchers have found that some ganglia are harder to reach than others. Over the years, they discovered that some AAV strains are better suited than others to find specific types of nerve clusters, and this has helped them fine-tune the selection of these delivery viruses to match infected cells in different places.

In their mouse experiments, the team continued to improve their results, nudging them up to a 95% reduction in herpesvirus infection in one prominent nerve cluster using a selection of two different meganucleases carried by three different flavors of AAVs. By selecting vectors that are primed for harder-to-reach nerve clusters, the group expects to continue improving their ability to eradicate the virus.

As the Jerome Lab prepares to see if its gene therapy can block genital herpes, they are also reshuffling their selection of vector viruses and meganucleases to target nerve cells infected by HSV-2.

They are collaborating with Dr. Barry Stoddard, a Hutch colleague who specializes in discovering the structure of proteins, to custom-design a set of meganucleases that they hope will work even better than the first.

“The three enzymes they use already work pretty well, but one doesn’t quite work as well as the others,” Dr. Stoddard said. “We’re looking at the structure and determining a few changes to improve performance.”

Stoddard is also tweaking the meganucleases’ structures to make them a better fit against HSV-2.

In their latest paper, the team evaluated the use of a newer and more glamourous gene-cutting tool, CRISPR-Cas9. Somewhat surprisingly, they found that this newfangled precision cutting tool did not perform as well as their meganucleases.

One possible reason: CRISPR is a much larger molecule, and the comparatively smaller meganucleases are easier to package and deliver to nerve cells.

Stoddard said that meganucleases can also more accurately zero in on their target genes than CRISPR, which is known for its “off-target” effects — cutting the wrong gene. The advantage of CRISPR is that it can be designed quickly, while meganucleases are laborious to make.

”It can take a day to make a new CRISPR. It takes about three months to make a meganuclease," Stoddard said.

Experience has shown, however, that the Jerome Lab is endowed with patience. Their 10-year trek has proven the potential of gene therapy for erasing herpes, yet the road ahead will undoubtedly require deep reserves of patience and persistence.

Although the antiviral drug acyclovir can knock down an outbreak of HSV-2, the virus lingers for a lifetime within infected nerve cells and may reactivate, causing recurrent bouts of painful sores, on average, up to 7 times per year.

The prevalence of this chronic disease increases with age. Less than 1 percent of teens in the USA are infected, but that increases to 21 percent of Americans in their 40s, according to the Centers for Disease Control and Prevention.

This new research was supported by the Caladan Foundation and the National Institutes of Health. Meganucleases used in the experiments described in the Nature Communications paper were supplied by Paris-based Cellectis SA. Scientists at Fred Hutch played a role in developing these discoveries, and Fred Hutch and certain of its scientists may benefit financially from this work in the future.

Herpes vaccine candidates are in various stages of clinical research and are listed on this PrecisionVaccinations webpage.

PrecisionVaccinations publishes research-based herpes vaccine news.

Sub Title:

Herpes virus targeted by gene cutting enzymes

References:

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Oral Herpes Rates Declining in Europe

Don Hackett — Fri, 24 Jul 2020 13:55:28 +0000

Reviewer:

Herpes simplex virus type 1 in Europe: systematic review, meta-analyses and meta-regressions

Over 65 percent of young people have their first sexual activity unexposed to herpes, but risk catching it in adulthood, stated a new study.

This research found fewer people are being exposed to herpes simplex type 1 (HSV-1), also known as oral herpes in their youth.

HSV-1 is mainly transmitted by oral-to-oral contact during childhood, causing oral herpes, but it can also cause genital herpes. The other form of the virus (HSV-2) is sexually transmitted and causes genital herpes.

Furthermore, this research published in BMJ Global Health on July 16, 2020, suggests the prevalence of oral herpes amongst Europeans is falling by 1 percent per year.

This study’s findings indicate the prevalence of the herpes virus, which often manifests itself with cold sores, appears to be declining in younger people.

Previous research data focused on North America and Europe has suggested that there is a decrease in the acquisition of HSV-1 in childhood, a decline in its population prevalence in youth, and an increase in genital herpes cases that are caused by HSV-1.

For this study, a team of researchers from Weill Cornell Medicine-Qatar of Cornell University set out to examine the epidemiology of HSV-1 in Europe.

They systematically reviewed HSV-1 related publications, conducted various meta-analyses, assessed pooled prevalence rates in populations, and estimated pooled proportions of HSV-1 viral detection in clinically diagnosed genital ulcer disease and in genital herpes.

Their analysis gathered information from 142 suitable previous publications. From these publications, they extracted 179 overall population prevalence measures, four overall proportions of HSV-1 in genital ulcer disease, and 64 overall proportions of HSV-1 in genital herpes.

The results showed that more than two-thirds (67.4%) of the population in Europe tested positive for HSV-1, which is far lower than the historical level of universal infection in childhood in other parts of the world, such as Africa.

Around 32.5% of children and 74.4% of adults were infected in Europe.

Prevalence in the population increased steadily with age, being lowest in those aged below 20 years and highest in those aged over 50 years.

The researchers speculated that reasons for falling prevalence rates of HSV-1 could include a general decrease in both family size and school crowding, as well as improved hygiene and living conditions.

The results also showed that half of the first-episode genital herpes cases in Europe were already due to HSV-1, as opposed to HSV-2 infection.

Both forms of the herpes virus are lifelong and the World Health Organization (WHO) estimates there are 3.7 billion people under age 50 (67%) who have HSV-1 infection globally and 491 million people aged 15-49 (13%) worldwide with HSV-2 infection.

The study authors acknowledged that their systematic review had some limitations, primarily the unavailability of data for 25 of 53 European countries, and had comparatively less data for genital ulcer disease and genital herpes than population prevalence.

Nevertheless, these limitations did not appear to have posed a barrier to the interpretation of the results of the study, they said.

These researchers stated: “HSV-1 transition in Europe is leading to more heterogeneous and variable transmission by age and geography, and an increasing role for HSV-1 in genital herpes as a sexually transmitted disease.”

“The findings highlight the importance of disease surveillance and monitoring of HSV-1 seroprevalence and genital herpes etiology, and strengthen the case for an HSV-1 vaccine to limit transmission.”

Clinical researchers have been working on developing herpes vaccines in clinical trials focused on both therapeutic and preventive vaccine candidates, which are listed on this webpage.

Herpes vaccine news is published by Precision Vaccinations.

Sub Title:

European children HSV1 infection rate exceeds 32 percent

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Herpes Impacts Women’s Reproductive Health

Don Hackett — Sat, 02 May 2020 16:23:23 +0000

Reviewer:

WHO: Herpes simplex virus: global infection prevalence and incidence estimates, 2016

Kelley Lu, PharmD

A new study estimates about half a billion people are living with genital herpes, and several billion have oral herpes infections around the world.

Herpes simplex virus (HSV) infections are lifelong and characterized by periodic reactivations. Symptomatic and asymptomatic viral shedding is common for both types of herpes.

Thus, infected individuals can be asymptomatic, yet infectious, allowing these viruses to be transmitted unknowingly. This attribute contributes to the large global prevalence of herpes infections.

And this study reports HSV type 2 (HSV-2) infections disproportionately affected women.

This insight means that HSV has a substantial effect on the sexual and reproductive health of millions of people worldwide.

Published by the World Health Organization (WHO) on May 1, 2020, these European researchers highlight the need to improve the awareness of products to prevent and treat herpes cases.

This study estimates around 491 million people currently living with HSV-2 infection, 3.5 billion with oral HSV type 1 (HSV-1) infection, and 122 million –192 million with genital HSV-1, in those up to 49 years of age.

Herpes Overview

HSV type 1 (HSV01) is primarily transmitted by oral-to-oral contact and cause orolabial herpes, which is commonly known as cold sores.

Type 1 virus also causes rarer conditions, such as keratitis and other ocular sequelae, and encephalitis.

HSV-1 genital infection from oral-to-genital contact is becoming increasingly common, although reactivations are less frequent than for HSV-2.

HSV-2 is almost entirely sexually transmitted, causing genital herpes.

Genital HSV infection may be unrecognized or result in painful genital ulcer disease in a proportion of those infected.

Neonates can acquire HSV infection from genitally infected mothers during birth and from oral contact with caregivers postnatally.

Neonatal infection, although rare, has a high fatality and disability rate in surviving infants. There is no cure for herpes today, says the WHO.

Herpes treatments

Most herpes infections are self-limited and treatment is not always indicated or necessary.

The current WHO guidelines provide 6 treatment recommendations for genital HSV infections. A summary of recommendations for genital HSV infection treatments can be found here.

There are intravenous, oral, and topical antiviral herpes medications, such as acyclovir, famciclovir, and valacyclovir, that can help to reduce the severity and frequency of symptoms.

Herpes Vaccine Candidates

As of May 2, 2020, the U.S. Food and Drug Administration has not approved any herpes preventive vaccine. However, after many years of research, various herpes vaccine candidates are making progress to FDA approval.

These herpes vaccine candidates include, but are not limited to the following list:

HSV529 is a vaccine candidate that is classified as a replication-defective virus, where the virus possesses all the components of the wild-type HSV virus with the exception of two proteins UL5 and UL29 that are involved in viral DNA replication.
EXD-12 vaccine candidate is currently in preclinical testing for safety and efficacy as both a prophylactic and therapeutic vaccine for both Herpes Simplex Virus-1, HSV-1, and Herpes Simplex Virus-2, HSV-2.
GSK’s HSV Vaccine or SB208141 is in a double-blind, randomized, controlled phase 3 clinical study to assess the prophylactic efficacy and safety of gD-Alum/MPL vaccine in the prevention of genital herpes disease in young women who are herpes simplex virus (HSV)-1 and -2 seronegative.

This new study was funded by the WHO Department of Reproductive Health and Research, via support from the United States NIH (U01 AI108543).

The researchers reported these competing interests: KJL reports grants from WHO during the conduct of the study and outside the submitted work. KJL and KMET report a grant from GSK outside the submitted work. NJW reports grants from the National Institute for Health Research during the conduct of the study and grants from Pfizer Ltd outside the submitted work. SLG reports grants from NIH during the conduct of the study.

Herpes vaccine development news published by Precision Vaccinations.

Sub Title:

Genital or Oral Herpes cases exceed 1 billion

References:

WHO: Billions worldwide living with herpes

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Next-Generation Herpes Drug Development Platform Acquired

Don Hackett — Sun, 12 Jan 2020 12:58:01 +0000

Reviewer:

Candel Therapeutics acquires next-generation herpes drug development platform and manufacturing expertise

A Massachusetts based company developing viral immunotherapies across multiple tumor indications announced that it has acquired all of the Herpes Simplex Virus (HSV) based assets from PeriphaGen, Inc.

Announced by Candel Therapeutics on January 8, 2020, this acquisition consolidates a next-generation herpes drug development platform and manufacturing expertise that can be tailored to multiple tumor types and indications.

The acquired development platform enables precise modifications to the virus backbone, allowing customization of viral traits such as replication capacity, tissue specificity and the expression of a large number of payloads including immunomodulators.

In addition, Candel acquired PeriphaGen’s lead product candidate developed to address chemotherapy-induced peripheral neuropathy.

This product candidate has been rationally engineered to provide neuroprotective activity via high-level and durable expression of a neurotrophin peptide to specifically impacted nerve ganglia.

PeriphaGen’s two scientific founders, highly respected experts in Herpes vectorology and peripheral neuropathy, David Krisky, M.D., Ph.D. and James Wechuck, Ph.D., have joined Candel to support the continuous development of the platform and products.

Candel Therapeutics is a Needham, Massachusetts based biotechnology company developing its proprietary immuno-oncology platforms, including its Gene Mediated Cytotoxic Immunotherapy (GMCI™) and proprietary HSV based platform, for the treatment of solid tumors and associated neurological pathologies.

For more information, contact: Media & Investor Relations at info@candeltx.com

Vaccine development news published by Precision Vaccinations.

Sub Title:

Candel Therapeutics acquired all of the Herpes Simplex Virus HSV based assets from PeriphaGen Inc

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Florida Startup Developing Herpes Vaccine

Don Hackett — Thu, 12 Dec 2019 19:39:17 +0000

Reviewer:

New Startup Biotech Company Plans to Test Promising Herpes Vaccine for Both HSV-1 and HSV-2

Holly Lutmer PharmD

A Florida startup biotechnology company developing vaccines previously announced during July 2019 a herpes vaccine candidate was in pre-clinical, guinea pig model testing phase.

And, the Excell Biotech website says ‘We hope to publish preclinical data (regarding the EXD-12 vaccine) by year-end 2019.’

This is potentially good news since there is not an approved herpes vaccine available in the USA. But, as of December 12th, the company has not issued a status update.

Furthermore, Excell’s website says the ‘EXD-12 is a live attenuated vaccine candidate currently in preclinical testing for safety and efficacy as both a prophylactic and therapeutic vaccine for Herpes Simplex Virus-1 (HSV-1) and Herpes Simplex Virus-2 (HSV-2).’

Excell continues saying ‘We have produced Herpes Simplex Virus (HSV) particles and used transmission electron microscopy to confirm that they are intact and devoid of other contaminating viruses.”

‘The absence of contaminating viruses was further proven by Polymerase Chain Reaction testing.’

‘We have added layers of safety-switches in order to make our live attenuated herpes virus the safest “living” virus to date.’

‘Previous herpes vaccine studies have shown that in the production process, self rescuant viruses can arise and become wild-type.’

‘While research groups have used different safety switches individually, we combine at least 4 different layers that guarantee that no infectious virus can arise.’

Excell’s vaccine development strategy is focused on innovative research.

To protect that innovation, Excell filed a provisional patent application with the United States Patent and Trademark office for their EXD-12 HSV vaccine candidate on September 14th, 2018.

‘New data indicates that glycoprotein D acts as a decoy, so the immune system is not able to form an effective antibody response to other antigens. Without glycoprotein D, herpes becomes visible to the immune system and is also unable to spread between cells.’

A separate, unrelated study published online during October 2019, adds further context to this scientific finding.

This study published in Science Direct says ‘viral glycosylation has been investigated in the context of a number of envelope glycoproteins, including the envelope glycoprotein of human immunodeficiency virus-1 and envelope glycoprotein of dengue, Zika, and other flaviviruses.’

‘However, glycosylation on viruses is not limited to envelope glycoproteins.’

‘Many secreted viral proteins present glycans that are necessary for their respective functions, such as the secreted glycoprotein G of herpes simplex virus.’

This study’s findings indicate ‘a better understanding of viral glycobiology will provide further opportunities to rationally develop novel therapeutics and vaccines.’

Recent herpes vaccine news

Herpes is a common sexually transmitted disease that any sexually active person can get. Most people with the virus don’t have symptoms. Even without signs of the disease, herpes can still be spread to sex partners, says the CDC.

Several clinical trials have tested vaccine candidates against genital herpes infection, but there is currently no commercially available vaccine that is protective against genital herpes infection.

Previously, on August 9, 2019, the herpes simplex virus 2 HSV529 vaccine candidate was found safe and elicited neutralizing antibody and modest CD4+ T-cell responses in 60 HSV-seronegative adult male/female vaccinees in a phase 1 clinical study.

And, University of Pennsylvania researchers announced in September 2019, a trivalent nucleoside-modified mRNA-LNP vaccine is a promising candidate in an animal study, and is ‘ready for human trials.’

Without a preventive vaccine available, millions of herpes infected patients can only treat their symptoms with antiviral medications, which can generally shorten a herpes outbreak.

Randomized trials have indicated that 3 antiviral medications provide clinical benefit for genital herpes: acyclovir, valacyclovir, and famciclovir, says the CDC.

Valacyclovir is the valine ester of acyclovir and has enhanced absorption after oral administration. Famciclovir also has high oral bioavailability.

And, these antiviral medications make it less likely that you will spread herpes to a sex partner but do not cure the infection.

Furthermore, taken daily, these medications can also reduce the number of recurrences and decrease viral shedding, says the CDC.

And the CDC says ‘topical therapy with antiviral drugs offers minimal clinical benefit and is discouraged.’

Herpes antiviral medications are available at most pharmacies in the USA.

Herpes vaccine news is published by Precision Vaccinations.

Sub Title:

Excell Biotech EXD-12 is a live attenuated herpes vaccine candidate

References:

Excell Biotech Pipeline

EXD-12 Herpes Simplex Vaccine

CDC: 2015 Sexually Transmitted Diseases Treatment Guidelines

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NRF2 Transcription Factor Plays an Important Role in Herpes Infections

Don Hackett — Tue, 10 Dec 2019 18:41:03 +0000

Reviewer:

Single-cell RNA-sequencing of herpes simplex virus 1-infected cells connects NRF2 activation to an antiviral program

A recent study provides new insights into the early stages of a Herpes Simplex Virus 1 (HSV-1) infection and serves as a general blueprint for the investigation of heterogeneous cell states in virus infection.

This is important clinical research since an estimated 80 percent of the worldwide population is infected in a quiescent, latent form, of the HSV-1.

In this study published on October 25, 2019, researchers from the Berlin Institute for Medical Systems Biology (BIMSB) used single-cell RNA sequencing to better understand herpesvirus viral infections.

The Herpesviridae is a large and diverse family of enveloped, double-stranded DNA viruses with relatively complex genomes. Herpesvirus infection initiates a range of perturbations in the host cell, which remains poorly understood at the level of individual cells.

These BIMSB researchers wanted to know exactly what might encourage or slow a herpes infection.

They investigated differences in the way the infection progresses in individual cells and found that the NRF2 transcription factor plays a major role.

The authors say in this study published in Nature, that Nuclear factor erythroid 2-related factor 2 (NRF2) activation slows the progress of the infection.

NRF2 is a transcription factor involved in the detoxification of reactive oxygen species and has been more recently shown to regulate inflammatory and antiviral responses.

“I visualized changes in the regulation of each gene we investigated in a single cell. This showed us that the activation level of the NRF2 transcription factor can be a marker for temporary resistance to HSV-1 infection,” says Dr. Vedran Franke, in a related press release.

The condition of the cell also seems to be decisive.

This study found that a cell is more vulnerable to HSV-1 infection during some phases of the cell cycle than others.

The study also presents another insight.

A medication that is currently being tested for patients with chronic kidney disease could inhibit herpes infection by activating the NRF2 transcription factor.

When the herpes virus enters host cells, it brings its own genetic information with it. This means that both human and virus genes are activated in the infected cells.

When this BIMSB research team treated these cells with the kidney drug – bardoxolone methyl – the virus became less productive.

It activated fewer of its own genes, which would normally fuel the infection.

The study authors believe this is due to the drug’s effect on the NRF2 transcription factor.

The BIMSB teamwork relies on a method that has been in use since 2016: single-cell RNA sequencing.

Conventional sequencing would allow the researchers to find out which genes in the investigated cells were active on average, but differences in the cells would not be visible.

The information produced with these methods is a bit like a fruit smoothie, said these researchers.

‘If I put 10 types of fruit into a blender, I can roughly tell that the smoothie contains, say blackberries when I taste it.’

“With single-cell RNA sequencing, we aren’t making a smoothie – we’re making a fruit salad.’

‘I can immediately identify the blackberries and say exactly how many are in the salad.”

Recent herpes vaccine news

Researchers have previously used conventional RNA sequencing to identify roughly 70 HSV-1 genes that are activated in the host cell.

“Up until now, it was only known that the genes US1 and UL54 are active in a group of cells at the same time,” says Dr. Emanuel Wyler.

The new study shows that some cells activate only one of the two genes.

“But we don’t know why just one of them is activated.”

Drs. Wyler and Franke say that all the results presented in their paper were only possible with single-cell RNA sequencing.

These authors see their work as a blueprint showing how single-cell RNA sequencing can help us understand viral infections. They are already planning to use the method to analyze 2 other viruses.

In the USA, there are currently antivirals approved by the U.S. Food and Drug Administration (FDA) for the treatment of genital herpes. They are acyclovir (Sitavig and Zovirax), valacyclovir (Valtrex), and famciclovir (Famvir).

But, there are no FDA approved herpes prevention vaccines, as of December 10, 2019.

One herpes vaccine candidate in a phase 1 trial is HSV529.

HSV529 is a vaccine candidate that is classified as a replication-defective virus, where the virus possesses all the components of the wild-type HSV virus with the exception of two proteins UL5 and UL29 that are involved in viral DNA replication.

This replication-defective HSV2 vaccine can infect cells and should result in a broader immune response.

Herpes Vaccine news published by Precision Vaccinations

Sub Title:

Berlin Institute for Medical Systems Biology researchers used single-cell RNA sequencing to better understand herpesvirus infections

References:

Fighting the herpes virus

Nrf2 Negatively Regulates Type I Interferon Responses and Increases Susceptibility to Herpes Genital Infection in Mice

Therapeutic Class Overview: Herpes

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Herpes & HIV Have a Strong Biological Association

Don Hackett — Thu, 05 Dec 2019 20:40:33 +0000

Reviewer:

Global and regional estimates of the contribution of herpes simplex virus type 2 infection to HIV incidence

A recent study said ‘a large burden of Human Immunodeficiency Virus (HIV) is likely attributable to a Herpes Simplex Virus type 2 (HSV-2) infection.

This study published in The Lancet estimated 420,000 of 1.4 million sexually acquired incident HIV infections were attributable to HSV-2 infection.

This is important news which suggests there is a strong biological association between HIV and HSV-2 infections.

This new systematic review and meta-analysis of 55 prospective studies through May ’19, was published on November 18, 2019, found ‘the adjusted risk of HIV acquisition to be at least tripled in individuals with HSV-2 infection.’

Specifically, an HSV-2 infection increases susceptibility to HIV acquisition, because both viruses increase the transmissibility of the other.

Furthermore, HSV-2 disease can become severe among people with HIV-related immunosuppression.

This means, ‘an HSV-2 infection is an important risk factor for HIV acquisition, and people with known HSV-2 infection could benefit from heightened HIV prevention efforts.’ such as pre-exposure prophylaxis (PrEP).

The best characterized biological association (cofactor effect) between HSV-2 and HIV is the effect of HSV-2 infection on HIV acquisition.

These researchers said the ‘biological plausibility for a cofactor effect of HSV-2 infection on HIV acquisition is compelling: ulcerative first episodes and recurrences of HSV-2 infection result in disruption to the epithelial barrier, which facilitates the entry of HIV.’

The recruitment of immune cells to control initial HSV-2 infection and frequent reactivations (viral replication and shedding from the genital area) concentrates target cells for HIV in the genital area.

Immune cells are recruited to the genital area regardless of whether viral reactivation is accompanied by symptoms, and this effect is seen even after 2 months of valaciclovir therapy.

Biological data are consistent with the finding that HIV acquisition risk is higher for individuals recently infected with HSV-2 than for those with established infection, as the first (symptomatic) episode of infection is longer in duration and more severe than subsequent recurrences and the number of days with recurrences and viral shedding, and thus with mucosal inflammation, is highest in the 1st year.

This study’s estimate of the global and regional population attributable fraction (PAF) was calculated by incorporating HSV-2 and HIV infection data with pooled relative risk (RR) estimates.

Because HSV-2 and HIV have shared sexual and other risk factors, in addition to HSV-related biological factors that increase HIV risk, only RR estimates that were adjusted for potential confounders were used.

New preventive interventions against HSV-2 infection could not only improve the quality of life of millions of people by reducing the prevalence of herpetic genital ulcer disease but could also have an additional, indirect effect on HIV transmission

In conclusion, these researchers said ‘we produced the first global and WHO-regional estimates of the potential contribution of HSV-2 infection to the HIV epidemic.’

‘These estimates are needed for improving our understanding of the extent to which HSV-2 infection contributes to HIV infections and how this varies across populations, which in turn informs where future intervention efforts would be best targeted to have maximum impact.’

‘Interventions targeted against HSV-2, such as new vaccines, have the potential to improve the lives of millions of people by reducing recurrent genital herpetic symptoms.’

‘In addition, in the presence of an effect of HSV-2 infection on HIV acquisition, prevention measures against HSV-2 transmission could have a further, indirect benefit on HIV.

Recent HSV-2 vaccine news

Previously, the HIV Prevention Trials Network 071 study conducted in southern Africa, HIV prevalence was found to be 41 percent in individuals with HSV-2 infection compared with just 6 percent in those without an HSV-2 infection.

Study limitations: We were unable to account for uncertainty in the proportion of individuals with recently acquired HSV-2 infection, which might, in principle, have led to an underestimation of uncertainty in the PAF estimates. However, this underestimation is unlikely because, as noted above, individuals with recently acquired HSV-2 infection are a minority and as a result contributed little to the PAF estimates.

A second limitation of the PAF estimates is that, by definition, they assume a causal link—in this case, an association between HSV-2 and HIV that is not solely a reflection of confounding.

HIV vaccine news

Recently, the US Department of Health and Human Services (HHS) announced on December 3, 2019, the Ready, Set, PrEP program that makes medications for PrEP taken to prevent HIV available at no cost to people without prescription drug insurance coverage.

When taken as prescribed, PrEP is highly effective at reducing an individual’s risk of acquiring HIV, says HHS. Gilead Sciences Inc., the producer of this product, has agreed to donate enough of its HIV medicines for 200,000 individuals over 10 years.

NOTE: Eligibility requirements are available at GetYourPrEP.com or by calling 855-447-8410.

Potential research conflicts: KJL reports grants from WHO during the conduct of the study and outside of the submitted work. NJW reports grants from the UK National Institute for Health Research during the conduct of the study and from Pfizer outside of the submitted work. M-CB reports grants from WHO outside of the submitted work. SLG reports grants from the US National Institute of Allergy and Infectious Diseases during the conduct of the study. All other authors declare no competing interests.

Herpes vaccine news published by Precision Vaccinations.

Sub Title:

HSV-2 infection increases susceptibility to HIV acquisition because both viruses increase the transmissibility of the other

References:

Effect of HSV-2 infection on subsequent HIV acquisition: an updated systematic review and meta-analysis

Population Effects of Antiretroviral Therapy to Reduce HIV Transmission (PopART)

Prevalence and Determinants of Herpes Simplex Virus Type 2 (HSV-2)/Syphilis Co-Infection and HSV-2 Mono-Infection among Human

Health program offers free HIV prevention drug to uninsured

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Herpes Virus Linked to Multiple Sclerosis

Don Hackett — Wed, 04 Dec 2019 12:45:47 +0000

Reviewer: