New Twin Study Suggests CMV Plays a Key Role in Shaping the Immune System

A recent Stanford University twins study concluded that environmental forces are more influential than genes when it comes to determining the make-up of an individual’s immune system. The study, led by Stanford immunologist Mark Davis, compared 210 identical and fraternal twins between 8 and 82 years old.

After analyzing blood samples that tracked 200+ immune system parameters including cell population frequencies, cytokine responses, and serum proteins, researchers found that in three-quarters of the measurements, differences between pairs of twins were strongly linked to non-heritable factors such as vaccinations, diet, and previous infections. Notably, a key environmental cause of immune system variation was the presence cytomegalovirus (CMV).

CMV is a common chronic infection affecting three in five Americans, and while usually harmless, CMV can pose a health threat to immune-compromised individuals and babies infected congenitally. Once CMV is in a person’s body, it remains for life.

The Stanford team examined 16 pairs of identical twins where only one was infected with CMV, and found significant variance in nearly 60% of the parameters studied. Specifically, CMV-discordant twins showed less similarities for many immune cell frequencies such as effector CD8+ and gamma-delta T cells. Similar results were seen in signaling responses to IL-10 and IL-6 stimulation, as well as in the concentrations of these same cytokines in serum.

Overall, the study confirmed that CMV’s influence was widespread, affecting 58% of the 204 immune system measurements. These findings demonstrate how a single chronic viral infection can dramatically alter the immune system’s composition and responsiveness.

The study’s authors concluded that when the immune system is tasked with a lifelong need to control a viral infection like CMV, it may create a broad shift in the magnitude and complexity of many cell subsets. Research suggests that as many as 10% of all T cells in CMV positive individuals may actively restrain viral replication and prevent disease.


New Study Lends Support to Possible CMV-Glioblastoma Connection

Glioblastoma (GBM) is among the most common and most aggressive malignant primary brain tumors in humans, accounting for approximately 15% of all cases. While brain cancer has many potential risk factors, including smoking and alcohol consumption, researchers have also identified a possible link between GBM and various pathogenic infections such as cytomegalovirus (CMV).

Numerous previous studies have confirmed that CMV nucleic acids and genes are present in more than 90% of some GBM tumors. A new study led by researchers at the California Pacific Medical Center expands on existing research and published articles and explores the connection between CMV and glioma stem-like cells (GSC). According to the study’s authors, existing data supports the idea that long-term, low-level CMV infection may promote the survival, stemness, and proliferation of glioma stem-like cells and could significantly contribute to GBM pathogenesis.

Glioma stem-like cells, like some other malignant tumors, exhibit features of self-renewal and have the ability to initiate and sustain tumor growth, metastasis, and resistance to therapy. Glioma stem-like cells are characterized by resistance to radiation and chemotherapy and are primarily responsible for GBM recurrence.

Based on the hypothesis that a specific CMV gene signature may be associated with GBM pathogenesis, study researchers used glioma cell lines and primary glioma stem-like cells infected with clinical and laboratory CMV strains, and measured relative viral gene expression levels along several time lines, up to 15 weeks post-infection.

Researchers concluded that while CMV gene expression was detected in several infected glioma lines through week five, only CMV-infected glioma stem-like cells expressed viral gene characteristics at the 15 week mark. A significant finding was that CMV-infected glioma stem-like cells outlived their uninfected counterparts, and this extended survival was paralleled by an increased frequency of tumor sphere formation and an increase in stemness regulators, including BMX, a novel CMV target first identified by the California Pacific Medical Center study.

Overall, the data support the theory that long-term, low-level CMV infection plays a critical role in the survival, stemness, and reproduction of glioma stem-like cells and could significantly contribute to GBM development and progression.

Researchers are continuing to study the relationship between CMV, GBM, and other types of cancer, including prostate, colon, and breast cancer. Clinical trials to evaluate the efficacy of CMV-specific cellular immunotherapy for GBM are also underway. With the increasing amount of evidence regarding the CMV-GBM connection, there is also growing interest in exploring vaccination against CMV antigens as a component of emerging immunotherapeutic strategies against GBMs and other malignant tumors.


VBI Partners with Le Classique to Raise CMV Awareness in Canada

VBI is pleased to announce its sponsorship support of Le Classique, a 3-on-3 ball hockey tournament being held in Winnipeg, Canada on February 5th – 8th, 2015. Now in its third year, Le Classique is expected to draw over 2,000 individuals seeking to broaden congenital cytomegalovirus (“CMV”) public awareness.

“Le Classique founders Marc Foidart and Rob Tetrault have combined their love of hockey with a very worthy cause,” said Jeff Baxter, VBI’s President and CEO. “We look forward to supporting Le Classique in their efforts to raise CMV awareness in Winnipeg and throughout Canada.”

Originally founded in Canada, VBI maintains close ties to the country and its people. VBI’s research facilities and the majority of its workforce are located in Ottawa, Ontario. In addition, VBI has participated in several Canadian government sponsored programs which have allowed the company to more quickly advance its product candidates.

CMV is among the most common congenital infections in Canada, causing a host of prenatal developmental delays. Despite its prevalence, awareness of CMV among women of reproductive age remains low. A 2012 study published in Preventative Medicine revealed that only 7% of men and 13% of U.S. women surveyed had heard of congenital CMV.

“Until a vaccine can be developed and deployed, awareness is the best current tool we have to prevent future infections,” said Le Classique founder Rob Tetrault. “Women contemplating pregnancy need to be made aware of the condition so they can understand and better manage potential infection risks.”

100% of the proceeds from Le Classique will be donated to the Canadian CMV Foundation. To make a contribution, or to learn more about Le Classique, visit: http://www.leclassique.ca.


New Study Examines CMV Shedding Patterns in Healthy CMV-Seropositive Children

Cytomegalovirus (CMV) is a highly contagious virus that is spread by direct contact with bodily fluids. To better understand potential transmission risks from contact with the body fluids of children, a recent study monitored weekly and daily CMV shedding patterns in healthy CMV-seropositive children.

While many studies have examined CMV shedding among healthy children, few have collected longitudinal data and none have assessed CMV shedding at weekly or daily intervals.

Researchers selected study participants for longitudinal follow-up from a sample of healthy children aged 0 – 47 months. The participants were selected from the Atlanta, Georgia metropolitan area and did not have a diagnosis of congenital CMV infection. To meet the follow-up criteria, the children had to test positive for anti-CMV IgG; 50 of 161 children qualified. Of these children, researchers enrolled 23 of 25 who also tested positive for CMV DNA in saliva and/or urine. In addition, the study included some CMV-seropositive non-shedders, allowing researchers to assess spontaneous initiation of shedding.

During the course of the study, each child received 12 weekly in-home visits at which field workers collected saliva and urine. During the final two weeks, parents also collected saliva and urine samples daily.

The study found that children who had contracted CMV and were shedding at the first screening visit continued to exhibit occasional shedding in weeks 11 and 12. In addition, children shedding at the screening visit had CMV DNA in 84% of follow-up saliva specimens and 28% of follow-up urine specimens. Median and mean viral loads did not change substantially over time, but shedding occurred at higher viral loads among younger children. These finding suggests that young CMV shedders pose an ongoing risk to pregnant women.

Another significant finding was the surprisingly high viral loads in the saliva of healthy young children. Of the 502 CMV DNA-positive saliva samples collected, nearly half contained greater than 100,000 copies/mL and more than one quarter had greater than 1×106 copies/mL. While several studies have measured CMV viral loads among children with congenital CMV infection, only two previous studies have measured viral loads among healthy children. This is significant because healthy children are most likely to infect pregnant women due to behavioral habits like sharing food or utensils.

Using this data, researchers hope to encourage behavioral changes in women who may be unaware of the risks posed by CMV. CMV infection is a significant cause of birth defects and developmental disabilities, including hearing loss, vision loss, and intellectual disability. Although congenital CMV infection is among the most common causes of developmental delays, few women are aware of the virus and the hygienic strategies needed to prevent transmission.

According to the Centers for Disease Control and Prevention (CDC), simple measures like frequent hand washing after contact with young children, kissing children on the forehead rather than the lips, avoiding the sharing of food or beverages, and disinfecting toys and countertops can help prevent the spread of CMV.

Preventing primary or re-infection of CMV through behavioral changes is of great importance, especially for women of childbearing age. While there is currently no licensed vaccine or established treatment plan for pregnant women, the Institute of Medicine ranks development of a vaccine to prevent CMV as a “highest priority” item.


Researchers Investigate Possible Link between CMV Infection and Atherosclerosis

Acute coronary syndrome (“ACS”) is an umbrella term that describes any condition brought on by sudden, reduced blood flow to the heart. ACS is often caused by atherosclerosis, the accumulation of plaque that can clog arteries.

While there are a number of known hereditary and lifestyle risk factors for ACS, researchers are exploring the role inflammation may play in the development of both ACS and atherosclerosis. One potential cause of inflammation may be cytomegalovirus (“CMV”) infection.

The relationship between CMV and atherosclerosis has been a subject of interest for a number of years. In a 2006 study, coronary plaque specimens from 38 patients who underwent a heart catheterization procedure were divided into an ACS group and a non-ACS group. Using special stains designed to detect CMV, researchers found the ACS group had a higher number of CMV-infected cells. The investigators concluded that CMV in the coronary plaque may be linked to the development of artery blockages.

In a more recent study, researchers examined CMV infection in 105 patients with atherosclerosis who received coronary artery bypass grafts. After adjusting for other risk factors, researchers concluded that patients with a history of ACS were more likely to test positive for CMV. Finally, in a 2012 meta-analysis of 55 prior studies, investigators concluded that CMV infection is associated with the progression of atherosclerosis, especially in Asian populations.

While these studies show that CMV may be linked to the development of atherosclerosis and ACS, the exact mechanism by which CMV affects vascular health is less well understood. Some recent research suggests that CMV and platelets may interact in a way that leads to inflammatory and angiogenic responses, which may exacerbate tissue damage and contribute to the formation of plaque in the inner lining of arteries.

By age 40, between 50% and 80% of U.S. adults will have had a CMV infection. Following the primary infection, the CMV virus typically remains dormant, but it can periodically reactivate, especially in immunocompromised persons.


VBI to Present at the LD Micro Conference

VBI will present at the LD Micro Conference on Wednesday, December 3rd at 9:00 AM PT. The event is being held in Los Angeles, CA at the Luxe Sunset Boulevard Hotel.

At the conference, Jeff Baxter, VBI’s President and CEO, will discuss current company developments and will meet with select investors for one-on-one meetings. For additional information, visit: http://ldmicro.com/companies/vbiv/

“Having only recently made our NASDAQ debut, we are pleased to share our progress with a broader community of investors,” commented Mr. Baxter. “We continue to make progress on multiple fronts, including on the development of our lead candidate, a prophylactic Cytomegalovirus (“CMV”) vaccine.”

Following the conference, VBI’s corporate presentation will be made available in the Investor Relations section of VBI’s website: http://ir.vbivaccines.com/presentations


New Study Explores Breast Milk as Postnatal CMV Transmission Source in Premature Infants

Very low birth weight infants fed breast milk from cytomegalovirus  (“CMV”)-positive mothers may be at an increased risk of developing postnatal CMV infection, says a new study published in JAMA Pediatrics.

Premature infants with very low birth weight (“VLBW”) are particularly vulnerable to CMV infection because of their immature immune systems. CMV infection can cause serious disease and, in some cases, can lead to death.

In one of the largest studies of its kind, investigators evaluated blood transfusions and breast milk as potential CMV transmission sources. 539 infants in three neonatal intensive care units were tested at birth for evidence of congenital CMV infection, and again at regular intervals for ninety days.

29 out of the 539 infants acquired a postnatal CMV infection during the course of the study. Five infants infected with CMV developed severe disease or died. 27 of the 28 CMV infections occurred among infants fed CMV-positive breast milk. No CMV infections were linked to blood transfusion (blood products were CMV-seronegative and leukoreduced).

The study’s investigators estimate that between 10-20% of VLBW infants who are fed CMV positive breast milk from mothers with a history of CMV will develop postnatal CMV infection. In this study, 76% of mothers had been infected with CMV prior to giving birth.

Importantly, despite the potential risk, The American Academy of Pediatrics (“AAP”) Policy endorses routine breast milk feedings, even in CMV seropositive mothers. The AAP Policy suggests that benefits of breast milk feedings may outweigh the risks.


New Study Explores Breast Milk as Postnatal CMV Transmission Source in Premature Infants

Very low birth weight infants fed breast milk from cytomegalovirus  (“CMV”)-positive mothers may be at an increased risk of developing postnatal CMV infection, says a new study published in JAMA Pediatrics.

Premature infants with very low birth weight (“VLBW”) are particularly vulnerable to CMV infection because of their immature immune systems. CMV infection can cause serious disease and, in some cases, can lead to death.

In one of the largest studies of its kind, investigators evaluated blood transfusions and breast milk as potential CMV transmission sources. 539 infants in three neonatal intensive care units were tested at birth for evidence of congenital CMV infection, and again at regular intervals for ninety days.

29 out of the 539 infants acquired a postnatal CMV infection during the course of the study. Five infants infected with CMV developed severe disease or died. 27 of the 28 CMV infections occurred among infants fed CMV-positive breast milk. No CMV infections were linked to blood transfusion (blood products were CMV-seronegative and leukoreduced).

The study’s investigators estimate that between 10-20% of VLBW infants who are fed CMV positive breast milk from mothers with a history of CMV will develop postnatal CMV infection. In this study, 76% of mothers had been infected with CMV prior to giving birth.

Importantly, despite the potential risk, The American Academy of Pediatrics (“AAP”) Policy endorses routine breast milk feedings, even in CMV seropositive mothers. The AAP Policy suggests that benefits of breast milk feedings may outweigh the risks.


Congenital CMV 101: From Prevention to Treatment

Dr. Michael Cannon, a research epidemiologist at the CDC’s National Center on Birth Defects and Developmental Disabilities, discusses congenital cytomegalovirus. This webinar was originally presented by Dr. Cannon on behalf of the CMV Public Health & Policy Conference.

CMV infection is a major health concern for expecting mothers, with 30,000 U.S. children born with the virus each year. Congenital CMV infection (cCMV) occurs when the virus is transmitted to a baby before birth, often by a mother who is unaware of the infection. While only ten percent of infants congenitally infected with CMV display symptoms, one in six children born with CMV, or more than 5,000 children annually, go on to develop permanent complications including hearing loss, vision loss, and intellectual disabilities.

The number of children impacted by CMV is greater than the number of children affected by fetal alcohol syndrome or Down syndrome. cCMV is responsible for one in five cases of infant hearing loss, and more than $1B per year is spent on persons affected by CMV.

Spread of Infection

CMV is transmitted through direct contact with bodily fluids, most often saliva and urine. CMV seropositive children are a major source of infection due to their high viral loads and shedding. CMV is easily spread among children with infected siblings. Parents with a child who is shedding the virus have a 25 percent chance of infection. Because they work with young children, day care workers are at particularly high risk of infection.

Interventions

Possible interventions to reduce the occurrence of cCMV include prenatal screening, behavioral modification (e.g., the avoidance of behaviors that could result in transmission, like sharing utensils or kissing on the lips), treatment to prevent fetal infection (with antiviral therapies), and early detection and intervention immediately after birth. Currently none of these interventions are routine in the U.S. Utah is the only U.S. state to mandate testing for cCMV in newborns who display hearing loss.

Treatment

Current treatment options for newborns diagnosed with cCMV include antiviral drugs. Antivirals have been shown to have limited and perhaps temporary benefits including the reduction or elimination of CMV viral shedding.

Future Directions

In a 2011 survey published in the journal Pediatrics, many respondents viewed CMV screening favorably, with the majority somewhat or strongly agreeing that they would want to have their newborn tested for CMV, even when it is not performed routinely or if a small payment was required.

While there is currently no vaccine available to treat cCMV, the Institute of Medicine ranks development of a vaccine to treat CMV as a “highest priority” item. In addition, legislatures in two states, Connecticut and Illinois, have considered laws requiring screening for newborns who display signs of hearing loss.

Important Disclaimer: The use or display of content from the Centers for Disease Control and Prevention (CDC) does not imply endorsement or government sanction of any third party causes, ideas, websites, products, or services by the CDC, or by Dr. Cannon.


Congenital CMV 101: From Prevention to Treatment

Dr. Michael Cannon, a research epidemiologist at the CDC’s National Center on Birth Defects and Developmental Disabilities, discusses congenital cytomegalovirus. This webinar was originally presented by Dr. Cannon on behalf of the CMV Public Health & Policy Conference.

CMV infection is a major health concern for expecting mothers, with 30,000 U.S. children born with the virus each year. Congenital CMV infection (cCMV) occurs when the virus is transmitted to a baby before birth, often by a mother who is unaware of the infection. While only ten percent of infants congenitally infected with CMV display symptoms, one in six children born with CMV, or more than 5,000 children annually, go on to develop permanent complications including hearing loss, vision loss, and intellectual disabilities.

The number of children impacted by CMV is greater than the number of children affected by fetal alcohol syndrome or Down syndrome. cCMV is responsible for one in five cases of infant hearing loss, and more than $1B per year is spent on persons affected by CMV.

Spread of Infection

CMV is transmitted through direct contact with bodily fluids, most often saliva and urine. CMV seropositive children are a major source of infection due to their high viral loads and shedding. CMV is easily spread among children with infected siblings. Parents with a child who is shedding the virus have a 25 percent chance of infection. Because they work with young children, day care workers are at particularly high risk of infection.

Interventions

Possible interventions to reduce the occurrence of cCMV include prenatal screening, behavioral modification (e.g., the avoidance of behaviors that could result in transmission, like sharing utensils or kissing on the lips), treatment to prevent fetal infection (with antiviral therapies), and early detection and intervention immediately after birth. Currently none of these interventions are routine in the U.S. Utah is the only U.S. state to mandate testing for cCMV in newborns who display hearing loss.

Treatment

Current treatment options for newborns diagnosed with cCMV include antiviral drugs. Antivirals have been shown to have limited and perhaps temporary benefits including the reduction or elimination of CMV viral shedding.

Future Directions

In a 2011 survey published in the journal Pediatrics, many respondents viewed CMV screening favorably, with the majority somewhat or strongly agreeing that they would want to have their newborn tested for CMV, even when it is not performed routinely or if a small payment was required.

While there is currently no vaccine available to treat cCMV, the Institute of Medicine ranks development of a vaccine to treat CMV as a “highest priority” item. In addition, legislatures in two states, Connecticut and Illinois, have considered laws requiring screening for newborns who display signs of hearing loss.

Important Disclaimer: The use or display of content from the Centers for Disease Control and Prevention (CDC) does not imply endorsement or government sanction of any third party causes, ideas, websites, products, or services by the CDC, or by Dr. Cannon.