Synthetic Vaccine Platform Presented At Swine Flu Conference

The synthetic vaccine platform technology of Generex Biotechnology Corp. has been presented at the first International Swine Flu Conference in Washington, DC.

Douglas M. Powell, PhD, director of immunobiology at Antigen Express, a wholly owned subsidiary of Generex, described the advantages of suppressing a pandemic virus by next generation vaccines, such as Generex’s synthetic platform, which can be mass-produced using existing technology, more quickly and at lower cost than egg-based vaccines. New synthetic vaccine technology could help prevent infection and easen the severity of H1N1 in humans.

Traditional egg-based vaccines take months to develop and rely on live virus, which always carries the risk of infecting rather than inoculating. Generex’s proprietary synthetic vaccine platform does not use live virus, but instead arranges peptides to create a “snapshot” of the virus that activates the body’s T-cells to fight off the foreign invader, completely eliminating any risk of infection.

Generex’s vaccine platform is already in various stage clinical trials for avian flu, as well as prostate, breast and ovarian cancers, melanomas, SARS and HIV/AIDS.

In addition to the company’s vaccine platform technology, Generex has developed a range of products based on their proprietary RapidMist platform technology for drug delivery through the inner lining of the mouth, ensuring that there is no deposit in the lungs. The company’s flagship product, Generex Oral-lyn is an oral insulin spray product for the treatment of Type-1 and Type-2 diabetes, available to patients in certain overseas markets and in Phase III global clinical trials. Generex has also developed and markets a variety of over-the-counter products.

Pandemic Vaccines: European Market Update

Four ‘mock-up’ vaccines developed by Baxter, GlaxoSmithKline and Novartis have already been approved in the European Union based on earlier data generated with the H5N1 virus strain, which is similar to H1N1. These vaccines were developed in the knowledge that the virus strain would be changed in the event of a declared pandemic, to include the strain causing the pandemic. Altogether, they have been tested in more than 8,000 subjects. Decades of experience with seasonal influenza vaccines indicate that insertion of a new strain in a vaccine, as will apply with the change from H5N1 to H1N1 in the mock-up vaccines, should not substantially affect the safety or level of protection offered.

Approval of the H1N1 vaccine is expected to be given after satisfactory review of these data. Clinical trials with the H1N1 strain are currently being initiated or are ongoing. Initial results on the efficacy, immunogenicity and safety of the vaccine from these trials are expected from September 2009 onwards, and will also be reviewed as soon as they become available.

Flu Vaccine Produces Robust Immune Responses

New vaccine of Vical Incorporated against A/H1N1 pandemic influenza (swine flu) produced robust immune responses well above the accepted protection threshold in 100% of vaccinated mice and rabbits after a standard two-dose vaccine regimen. In addition, at least 75% of vaccinated animals achieved or exceeded the protection threshold after a single dose of vaccine. Vical Incorporated is ready to advance directly to large-scale cGMP manufacturing of the vaccine for human clinical trials, subject to securing external funding for this program.

“Our DNA vaccine technology offers an innovative approach to dealing with pandemics,” said Vijay B. Samant, President and Chief Executive Officer of Vical. “The speed of our platform both in development and manufacturing was demonstrated by our rapid completion of vaccine production and successful immunogenicity testing in animals while conventional vaccine manufacturers are still working toward production of their initial supply of H1 vaccine. We are encouraged by these compelling data with our Vaxfectin(r)-formulated DNA vaccine and we look forward to advancing to human clinical trials as soon as possible.”

Vical’s plasmid DNA vaccine contained the H1 hemagglutinin gene sequence provided by the U.S. Centers for Disease Control and Prevention (CDC) for the A/H1N1 influenza strain selected on April 30. The preclinical vaccine was produced by May 11 and animal testing began on May 15. In two parallel animal studies, one in mice and one in rabbits, vaccine was administered on Day 0 and Day 21, a standard regimen for pandemic influenza vaccines. Sera collected on Day 21, after a single dose of vaccine, showed clear increases over baseline hemagglutination inhibition (HI) titers in 100% of the animals, and HI titers above the protection threshold in 88% of the mice and 75% of the rabbits. Sera collected on Day 35, two weeks after the second dose, showed HI titers well above the protection threshold in 100% of the animals, ranging from 320 to 2,560 (geometric mean titer = 987) in the mice, and from 640 to 2,560 (geometric mean titer = 1,522) in the rabbits. The HI assay measures a vaccine’s ability to prevent viruses from binding to cells, and HI titers of 40 or more are accepted as the threshold for potential protection against influenza viruses. The vaccine encoded H1 hemagglutinin from the swine-origin A/California/04/09 wild-type influenza virus. Vical ran the HI assay against the swine-origin A/California/07/09 x-179a reassortant influenza virus obtained from the CDC.

About Vical
Vical researches and develops biopharmaceutical products based on its patented DNA delivery technologies for the prevention and treatment of serious or life-threatening diseases. Potential applications of the company’s DNA delivery technology include DNA vaccines for infectious diseases or cancer, in which the expressed protein is an immunogen; cancer immunotherapeutics, in which the expressed protein is an immune system stimulant; and cardiovascular therapies, in which the expressed protein is an angiogenic growth factor. The company is developing certain infectious disease vaccines and cancer therapeutics internally. In addition, the company collaborates with major pharmaceutical companies and biotechnology companies that give it access to complementary technologies or greater resources. These strategic partnerships provide the company with mutually beneficial opportunities to expand its product pipeline and address significant unmet medical needs. Additional information on Vical is available at www.vical.com.

Flu Vaccine Solution in Spain: VLP Technology

Novavax, Inc. announced initial agreement to license its proprietary, recombinant virus-like-particle (VLP) vaccine technology to ROVI Pharmaceuticals (Madrid: ROVI) of Spain. ROVI will use the VLP technology to create a comprehensive influenza vaccine solution for the Spanish government under a new 60 million euro program sponsored and led by the Spanish Ministry of Health and other government groups to develop pandemic and seasonal flu vaccines and establish its only in-border facility. This program, which was announced today by Spanish health officials, is being launched to develop safe and effective flu vaccines to serve the entire population of Spain.

ABOUT NOVAVAX
Novavax, Inc. (Nasdaq: NVAX) is a clinical-stage biotechnology company creating novel vaccines, including H1N1, to address a broad range of infectious diseases worldwide using advanced proprietary virus-like-particle (VLP) technology.

ABOUT ROVI
ROVI is a fully integrated, profitable Spanish specialty pharmaceutical company engaged in the research, development, in-licensing, manufacturing and marketing of small molecule and specialty biologic drugs.

DNA Vaccines against Swine Influenza A (H1N1) in Evaluation

Inovio Biomedical Corporation in collaboration with the National Microbiology Laboratory of the Public Health Agency of Canada and the University of Pennsylvania is evaluating DNA vaccine candidates against swine influenza A (H1N1) virus. These vaccines, delivered using Inovio’s proprietary electroporation technology, have the potential to provide protection against a broad scope of existing as well as currently unknown, unmatched influenza strains that could emerge - one of the perpetual challenges in trying to protect against influenza. The purpose of this evaluation is to test these vaccine candidates against pandemic and seasonal influenza strains in animal models and will include testing against a recently identified swine H1N1 strain.

Inovio scientists have created DNA vaccine candidates broadly targeting the H1N1, H2N2, H3N2, and H5N1 influenza sub-types, which make up the majority of seasonal and pandemic influenza.

Mice immunized with an Inovio H1N1 DNA vaccine were challenged with a lethal dose of the unmatched H1N1 virus. All the immunized mice survived the challenge (100% protection) to the end of the experiment and displayed significant protection from infection-associated morbidity. All the control mice died by day 8 after being challenged with the virus.

Protein Sciences Corporation Announced Production of H1N1 Swine Flu Vaccine

Protein Sciences Corporation (PSC) announced that it commenced manufacturing of a vaccine to protect humans against the H1N1 “swine flu” virus. The Company estimates that it can produce 100,000 doses this week and at least 100,000 doses per week thereafter. The vaccine, called PanBlok®, is made using PSC’s proprietary baculovirus and insect cell manufacturing technology. PSC claims that PanBlok is the first and only vaccine that could be used to protect against the escalating worldwide pandemic, at least for the next few months.

A week after Protein Sciences announced production of its vaccine, several creditors with total claims of about twelve million filed an Chapter 7 petition seeking bankruptcy for Protein Sciences Corporation.

About PSC
PSC is a privately held biopharmaceutical company based in Meriden, Connecticut, manufacturing innovative vaccines and biopharmaceuticals. PSC uses recombinant DNA technology to make novel human and veterinary prophylactic and therapeutic vaccines and diagnostics. The active ingredients in all of the firm’s products are recombinant proteins that are manufactured, using its patented protein expression technology, based upon baculovirus and insect cell technology.

China’s First Influenza A (H1N1) Vaccine Order Goes to Sinovac

On June 14, 2009, Sinovac completed construction of the H1N1 virus seed bank necessary to produce a virus antigen and commenced production of the first batch of H1N1 vaccine. Sinovac expects to complete production of the first batch by the end of July.

Few days later Sinovac Biotech Ltd. announced the first order in China to supply its influenza A (H1N1) vaccine to the Beijing government. The initial order consists of 4 million doses and is expected to be delivered by the end of September. This order will be administered to 2 million people in the high risk group. Additional orders are expected beginning in October and, in total, Sinovac expects to supply approximately 10 million doses to the Beijing government. The 10 million doses will be administered to 5 million people in Beijing.

About Sinovac
Sinovac Biotech Ltd. is a China-based biopharmaceutical company that focuses on the research, development, manufacture and commercialization of vaccines that protect against human infectious diseases. Sinovac’s vaccine products include Healive(R) (hepatitis A), Bilive(R) (combined hepatitis A and B), and Anflu(R) (influenza). Panflu(TM), Sinovac’s pandemic influenza vaccine (H5N1), has already been approved for government stockpiling. Sinovac is developing vaccines for enterovirus 71, universal pandemic influenza, Japanese encephalitis vaccine, and human rabies vaccine. Its wholly owned subsidiary, Tangshan Yian, is conducting field trials for independently developed inactivated animal rabies vaccines.

DNA Vaccine Platform: Reaching Milestones of $6 Million NIH Grant

Vical Incorporated has successfully completed second-year milestones under a three-year, $6.0 million grant awarded in 2007, and is advancing with the development of a DNA vaccine manufacturing process with the potential to produce several million doses of vaccines in a matter of days.

The RapidResponse(tm) system is designed to allow extremely rapid and large-scale production of DNA vaccines with low capital requirements. It is ideally suited to enable an immediate response against emerging diseases affecting large populations, such as H1N1 or H5N1 pandemic influenza or severe acute respiratory syndrome (SARS). The company is proceeding with the development of the RapidResponse(tm) platform under the third year of grant funding awarded by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH).

About Vical
Vical researches and develops biopharmaceutical products based on its patented DNA delivery technologies for the prevention and treatment of serious or life-threatening diseases. Potential applications of the company’s DNA delivery technology include DNA vaccines for infectious diseases or cancer, in which the expressed protein is an immunogen; cancer immunotherapeutics, in which the expressed protein is an immune system stimulant; and cardiovascular therapies, in which the expressed protein is an angiogenic growth factor. The company is developing certain infectious disease vaccines and cancer therapeutics internally. In addition, the company collaborates with major pharmaceutical companies and biotechnology companies that give it access to complementary technologies or greater resources. These strategic partnerships provide the company with mutually beneficial opportunities to expand its product pipeline and address significant unmet medical needs.

About the RapidResponse(tm) Platform
The RapidResponse(tm) DNA vaccine manufacturing platform is intended to significantly reduce the time required to develop, manufacture and deploy vaccines against emerging diseases during the early stages of an infectious outbreak. By using a cell-free manufacturing process, the company believes that the RapidResponse(tm) DNA platform can overcome the time, capacity and cost challenges of manufacturing conventional vaccines for diseases such as influenza, which use viruses grown in chicken eggs or via cell culture, requiring months of production time in large, dedicated facilities.

RapidResponse(tm) DNA vaccine manufacturing involves a cell-free process and single-step vaccine purification. The process has the potential to be scaled up by simply using larger equipment with no increase in production time, conceivably allowing production of hundreds of millions of doses of DNA vaccine during the earliest stages of an outbreak. Such speed and scale may be crucial in addressing a naturally emerging potentially pandemic disease such as influenza or SARS, an accidental release of a dangerous pathogen such as Ebola virus or Yersinia pestis (plague bacterium) from a biological containment facility, or an intentional release of a weaponized or bioterrorist-modified pathogen designed to cause diseases such as anthrax or smallpox.

Initial research testing demonstrated 100% protection of mice against a lethal challenge with an H3N2 influenza virus after a single 2 microgram dose of Vaxfectin(r)-formulated DNA vaccine produced by polymerase chain reaction (PCR). The goals in the final year of grant funding are to complete scale-up of vaccine production and complete animal safety testing.

The PCR process produces a segment of DNA, called a linear expression cassette (LEC), which includes only those DNA sequences essential for eliciting immune responses. The bacterial fermentation process typically used for DNA vaccines produces a closed loop of DNA, called a plasmid, which includes DNA sequences required by the bacteria in the manufacturing process. Vical holds patents in the United States and in other key regions based on the company’s discovery that administering polynucleotides such as DNA or RNA to tissues, without the use of viral delivery vehicles, may cause expression of the proteins encoded by the polynucleotides. Vical’s patent coverage includes delivery of linear DNA as well as plasmid DNA.

Currently plasmid DNA vaccines, which are under development against pandemic influenza and other infectious diseases at Vical, are manufactured by bacterial fermentation in standardized equipment with a production time measured in weeks rather than months. While plasmid DNA vaccines offer a significant improvement over conventional vaccine manufacturing technologies, the RapidResponse(tm) DNA vaccine platform could offer further advantages, especially in greater speed of production and lower cost. The company plans to continue development of its plasmid DNA vaccine programs because the technology is much closer to commercial realization in humans.

Related Post
Patent for Universal Influenza Vaccine Approach

Antibody-Based HIV Vaccine: New Approaches

According to John R. Mascola, M.D., deputy director of the Vaccine Research Center at the National Institute of Allergy and Infectious Diseases of the National Institutes of Health, several recent studies suggest promising new research directions for the development of an antibody-based HIV vaccine. Attempts to create a vaccine that induces antibodies that prevent HIV infection have so far been unsuccessful.

The receachers found that, contrary to widespread belief, it is not uncommon for people infected with HIV to naturally make antibodies that can neutralize a variety of HIV strains. These antibodies do not protect people from the virus because they arise years after HIV infection is established. However, if a vaccine could prime the body to make these broadly neutralizing antibodies before exposure to HIV, they could potentially prevent infection or hold the virus at bay until an army of immune cells assembles to limit viral replication.

Based on these findings, Dr. Mascola and colleagues designed a research strategy that uses naturally occurring, broadly neutralizing anti-HIV antibodies for the ultimate design of an antibody-based HIV vaccine.

Key aspects of this strategy:

• Obtaining new broadly neutralizing antibodies to HIV to expand the pool available for scientists to study
• Identifying regions on the surface of HIV that are vulnerable to broadly neutralizing antibodies and determining the atomic-level crystal structure of those regions
• Understanding how broadly neutralizing antibodies to HIV evolve and persist
• Clarifying the structural differences between anti-HIV antibodies that do and do not have neutralizing properties
• Determining what quantity of broadly neutralizing antibodies an HIV vaccine must elicit to be effective
• Learning how anti-HIV neutralizing antibodies and HIV surface proteins evolve in response to one another in people who eventually produce a powerful neutralizing antibody response to the virus
• Clarifying how HIV surface proteins are presented to the immune cells that produce broadly neutralizing antibodies to HIV
• Determining what immune-system conditions promote the production of broadly neutralizing anti-HIV antibodies

DoD Explores New DNA Vaccine Delivery Method

Connie Schmaljohn, senior research scientist at the U.S. Army Medical Research Institute of Infectious Diseases, announced that DoD scientists are exploring a new DNA vaccine delivery method at the webcast “Armed with Science: Research and Applications for the Modern Military”.

“DNA offers a number of advantages over conventional vaccine approaches, especially with regard to biodefense vaccines. This is important when rapid vaccine development is needed for a newly emerging disease threat or possibly for a genetically engineered biological warfare pathogen.”

One of the newest DNA vaccine delivery methods relies on technology known as the “gene gun,” which is capable of delivering the vaccine directly into cells. The needle-free vaccination method is more cost-effective and less painful for the recipient.

“The DNA is first coated onto very, very tiny gold beads, and those gold beads with the DNA are then put inside of a plastic device that’s about the size of a small flashlight. Inside that device is also a little canister of compressed helium gas. When the trigger of the gene gun device is pushed, the gas is released and it propels the gold coated with the DNA out of the device into the skin of the vaccine recipient.”

USAMRIID is conducting a human study of DNA vaccines using this delivery method. Schmaljohn’s research team has isolated small amounts of DNA from the Hantaan and Puumala viruses - known health threats to U.S. troops stationed in Europe and Asia to develop the vaccines. Both vaccines are in Phase I clinical testing, the first step toward licensure by the FDA.

“Its main goal is actually to prove that the vaccine is safe in humans, but of course, we’re also interested in determining if it’s inducing an immune response. The hantaviruses, once they infect humans, can cause one of two serious human illnesses: hemorrhagic fever with renal syndrome, which occurs in Asia and Europe, or hantavirus pulmonary syndrome, which occurs in the Americas. Today there’s more than 100,000 cases of hemorrhagic fever with renal syndrome each year, with the highest number occurring in China, Russia … Scandinavia and other parts of Europe.”

USAMRIID is producing a DNA vaccine for the Asian and European hantaviruses that can cause hemorrhagic fever with renal syndrome. This disease first was recognized as a threat during the Korean War.

These viruses are found in many types of rodents, including rats, field mice and meadow voles.

“They’re transmitted to humans in the aerosols of rodent’s urine, feces and saliva. The rodents that carry these viruses are persistently infected, and they show no signs of illness.”

Over tens of thousands of years, these viruses and rodents have formed a mutually exclusive relationship in which both have adapted to one another. While the virus doesn’t appear to affect the rodents’ health, the virus does pose significant risk to humans.