Researchers Explore Possible Link between CMV and Glioblastoma (GBM)

While many potential risk factors for brain cancer have been identified, including smoking and alcohol consumption, various pathogenic infections, including cytomegalovirus (CMV), may also constitute an under-appreciated but significant risk.

In 2011, there were an estimated 144,463 people living with brain and other nervous system cancers in the U.S. Glioblastoma (GBM) is considered the most common and most aggressive malignant primary brain tumor in humans, accounting for about 15 percent of all cases.

First described in 2002, the link between CMV and GBM has been championed by Dr. Charles Cobbs, a UCSF-trained neurosurgeon, who initially explored his hypothesis during off-hours and without formal research funding. Dr. Cobbs found that a high percentage of GBM tumors were infected with CMV; he also noted that the CMV virus resided in the tumor but not in the healthy tissue surrounding it.

A myriad of studies have since reinforced Dr. Cobbs’ findings. Using highly sensitive detection techniques, including PCR amplification, CMV nucleic acids and genes have been found in more than 90 percent of some GBM tumors.

Furthermore, a 2013 study found that CMV infection levels in GBM patients may predict survival. In that study, CMV infection was detected in 74 of 75 tumors – notably, prognosis differed based on the level of CMV infection – in patients with low-grade CMV infection, median survival was 20 months longer than in patients with high-grade infection. Presently there is no causal link between CMV infection and GBM development, though this research suggests that CMV may contribute to the progression of GBM.

In April 2011, oncologists and virologists involved in studying the relationship between CMV and GBM gathered in Washington, D.C. Based on published data, researchers concluded that CMV sequences and viral gene expression are present in most malignant brain tumors, and that CMV could modulate the progression of GBM by interacting with key signaling pathways. The researchers noted that future studies should focus on elucidating CMV’s role in tumor development.

At this time, it is unclear whether CMV plays an active role in glioblastoma progression or if it becomes reactivated under conditions that result in chronic inflammation or immunosuppression. GBMs are known to exert a variety immunosuppressive effects in patients, all of which could contribute to the establishment of environment that would permit CMV infection or reactivation at the tumor site.

Researchers are continuing to study the relationship between CMV, GBM, and other malignancies. Given that tumor-associated antigens are generally poorly immunogenic, there is growing interest in exploring vaccination against CMV antigens, which are highly immunogenic, as a component of new immunotherapeutic strategies against GBMs.


VBI to Present at the Sachs Associates Biotech in Europe Forum

Dr. David E. Anderson, VBI’s Senior Vice President of Research, will present this week at the Biotech in Europe Investor Forum. The two-day event will begin tomorrow, September 30th, in Basel, Switzerland.

Dr. Anderson will participate in a vaccines panel discussion co-chaired by Chris Britten, Head of Business Development at Sanofi Pasteur, and Dr. Florian Schödel, the founder of Philimmune, a consulting firm specializing in biologics and vaccines. Dr. Schödel also serves as a member of VBI’s Scientific Advisory Board.

The vaccines panel discussion will begin at 9:45AM Central European Time (UTC +01:00) on September 30th. Following the panel discussion, Dr. Anderson will deliver a presentation for investors at 4:20PM Central European Time (UTC +01:00) in Room Lima.

The Biotech in Europe Forum brings together leading late-stage private and public companies with investors, analysts, money managers, and pharma licensing executives. For more information, visit: http://www.sachsforum.com/basel14/index.html


Utah Leads the U.S. in CMV Screening and Education

Last year, Utah became the first state to pass legislation designed to improve CMV awareness and screening for those most at risk.

On June 14th, 2013, Governor Gary Herbert signed Utah House Bill HB0081, the first state level legislation dedicated to CMV. HB0081 establishes a public education program that requires healthcare providers to communicate the dangers of congenital CMV infection to pregnant women. HB0081 also mandates CMV screening for infants suffering from hearing loss.

In a 2007 literature review, Dr. Scott Gross, a Senior Health Economist at the CDC, found that 14% of children with congenital CMV infection went on to develop sensorineural hearing loss of some type. The literature suggests that 15% to 20% of cases of hearing loss could be attributable to congenital CMV infection.

Utah newborns who fail two hearing screenings are now required to undergo CMV testing within three weeks of birth. Infants with hearing loss who test positive for CMV are referred to the University of Utah, where healthcare providers provide treatment options and also teach parents how they can help limit future CMV transmission.

Because a child with CMV can spread the virus for years, education may be the best current option to reduce transmission of the disease. A 2012 study (a summary of which can be found here) revealed that only 7% of men and 13% of U.S. women surveyed had heard of congenital CMV. CMV is often transmitted through direct contact with bodily fluids, especially saliva, and many women engage in behaviors that put them at risk when interacting with children still in diapers, including kissing, sharing utensils, and sharing food.

As one of the most forward looking states when it comes to CMV awareness and prevention, Utah is also home to the CMV Public Health and Policy Conference, an event being held this September in Salt Lake City.


VBI to Present at the CMV Public Health & Policy Conference

  • VBI is developing a prophylactic CMV vaccine; VBI’s Senior Vice President of Research will discuss the vaccine candidate’s design, preclinical data, and manufacturing process.
  • The Presentation will begin at 10:45AM on Friday, September 26th in Ball Room A.

VBI Vaccines has been invited to speak at the CMV Public Health & Policy Conference being held in Salt Lake City, UT on September 26th and 27th.

Dr. David E. Anderson, VBI’s Senior Vice President of Research, will deliver a presentation, A Prophylactic CMV Vaccine to Prevent Congenital Infection Using Enveloped Virus-Like Particles (eVLPs), at 10:45AM on Friday, September 26th in Ball Room A. Dr. Anderson will discuss VBI’s CMV Vaccine Program and the Company’s lead product candidate, VBI-1501A.

VBI-1501A is a prophylactic vaccine designed to prevent CMV infection. VBI-1501A has demonstrated strong proof of concept in preclinical studies and is currently on track to support an IND submission and Phase I start in Q4 2015. For more information, visit: http://www.vbivaccines.com/cmv/.

“This exciting vaccine candidate could reduce or eliminate the developmental delays and birth defects caused by congenital CMV infection, for which today there is no vaccine available,” said Jeff Baxter, VBI’s President and CEO. “We are pleased to share our progress and also to support Utah State University and the CMV community in their efforts to limit the devastating effects of CMV in the near term.”

The goal of the CMV conference is to present the latest research on diagnosis and treatment, raise awareness, delineate prevention efforts, provide information about early intervention options, and to develop strategies to reduce the number of children born with CMV. For more information, visit the CMV Public Health & Policy Conference website at: http://cmv.usu.edu/.


Thermostable Vaccines: Overview and Market Opportunity

Each year, a significant portion of vaccines lose their potency, become ineffective, or can become hazardous due to problems in transportation and storage. These failures add to the overall cost of vaccines, limit availability, and threaten public safety.

VBI’s LPV™ technology enables the development of vaccines and biologics that can withstand storage or shipment at constantly fluctuating or elevated temperatures. Once commercialized, this technology could increase vaccine safety, efficacy, and access in both established and emerging markets. Learn more about our thermostable vaccine program  >>

The Vaccine Distribution Process and Its Shortcomings

The total established vaccine market was approximately $24B in 2013 with the large majority of vaccines requiring “cold chain” transportation to remain viable. The World Health Organization (WHO) estimates that nearly 50% of lyophilized (freeze-dried) and 25% of liquid vaccines are wasted each year.1 One of the biggest contributors to this wastage is disruption of the cold chain.

A break in the cold chain can reduce the efficacy or potency of a vaccine and in some cases can lead to toxicity or public safety concerns. In addition to maintaining the cold chain, there is a separate challenge of verifying any lapses in the chain and in testing the viability of the vaccine before it is administered, particularly in poor or remote areas.

Large public health organizations, including The Bill and Melinda Gates Foundation, have long advocated for innovations that will enable the development of more stable vaccines. However, the challenges of developing thermostable vaccines have been greater than expected. In a 2010 interview with the New York Times,2 Bill Gates commented that he hoped that there might be a single thermostable vaccine candidate by 2015. Five years earlier, he was optimistic that there would be a number of thermostable vaccines by 2010.

Vaccines vary greatly in their ability to remain viable under fluctuating temperatures. The stability of a particular vaccine formulation depends on many factors including the type of antigen (active ingredient) and the presence of other vaccine components such as adjuvants, stabilizers, and preservatives.


Liquid Vaccines Wasted


Lyophilized Vaccines Wasted

VBI’s LPV™ Platform

Changes in temperature degrade vaccines and other protein-based compounds by altering their molecular structure. VBI’s proprietary thermostable technology platform, known as LPV™, creates lipid vesicles (small lipid bubbles) which surround and enclose the antigen (active component) of a vaccine. These structures are then ‘freeze-dried’ in a process designed to improve vaccine stability.

VBI’s platform has several unique attributes that give a competitive edge in terms of speed, cost, flexibility, and consistency:

  • Based upon well-established lipid components: LPV™ is built upon novel fully synthetic lipid combinations with well-established safety profiles.
  • Technique can be used on different types of vaccines: LPV™ technology can be used for new or existing vaccine formulations; it has been used to stabilize several styles or ‘classes’ of vaccine antigen, including protein-based, whole-inactivated, and live-attenuated vaccines.
  • Simple and scalable process: The LPV™ process has been successfully tested in a GMP-compliant production plant at pilot levels. Data demonstrates that the process is consistent across batches, which should aid regulatory approval and market acceptance.
  • Long-lasting stability across a variety of conditions: LPV™ has demonstrated potency in multiple preclinical animal models, including non-human primates, and has demonstrated efficacy in mice and ferrets with aged vaccine formulations stored at 4° C and 40° C.

LPV™ Market Opportunity

Keeping vaccines in a narrow band of acceptable temperatures during shipment is challenging and expensive – the “cold chain” consumes about 80 percent of the total cost of vaccination programs according to the U.S. National Sciences Foundation (NSF).3

Annual expenditures on vaccines are estimated at $24B worldwide currently, up from $5 billion in 2000.4 WHO believes the market will grow up to 15% annual, reaching $100 billion by 2025.5 Improved thermostability can increase access to life-saving vaccines in emerging economies, a major area of growth in the vaccine market.

Thermostability technologies like LPV™ could provide vaccine manufacturers with a significant market advantages. Moreover, the critical issue of public health safety and strict quality controls could drive acceptance for LPV™ technology by governments and global health organizations, even in areas where a cold-chain already exists.

LPV™ Proof of Concept Studies

Sources

  1. Thermostability of vaccines, A. Galazka, J. Milstien, M. Zaffran, World Health Organization 1998.
  2. Five Years In, Gauging Impact of Gates Grants, New York Times, December 20, 2010
  3. http://firstlook.pnas.org/making-vaccines-not-need-refrigeration/
  4. http://who.int/influenza_vaccines_plan/resources/session_10_kaddar.pdf
  5. ibid