flu vaccine related Press Releases

VaxInnate's Universal Flu Vaccine Candidate Shown Safe and Immunogenic in Phase I Clinical Study

Calisha Myers — Thu, 30 Apr 2009 09:47:24 -0400

VaxInnate's Universal Flu Vaccine Candidate Shown Safe and Immunogenic in Phase I Clinical Study

Study validates proprietary technology that could transform flu vaccine production

WASHINGTON--(BUSINESS WIRE)--A universal flu vaccine candidate that could end the need for annual flu shots and provide protection against seasonal and pandemic flu strains was well tolerated and immunogenic in a Phase I study that was presented at the joint 48th ICAAC/46th IDSA annual meetings here today.

This first clinical study of VaxInnate's M2e universal flu vaccine candidate also validates the Cranbury, NJ-based biotechnology company's novel approach to developing and producing flu vaccines, which is based upon a proprietary combination of toll-like receptor (TLR)-mediated immune enhancement and recombinant bacterial production of vaccine antigen.

"VaxInnate's M2e universal flu vaccine candidate has passed a critical initial test," said David Taylor, MD, Chief Medical Officer. "We're encouraged by these data, which demonstrate that the vaccine is safe and elicits potent immune responses at doses below a microgram of vaccine antigen, and does so without the use of conventional adjuvants."

Safety & Immunogenicity Established

The multicenter, double-blind, randomized, placebo-controlled Phase I study was designed to assess the safety and immunogenicity -- a patient's ability to generate an immune response -- of four doses (0.3, 1, 3 and 10 μg) of the vaccine candidate. The vaccine candidate is comprised of the ectodomain of the viral M2 protein (M2e) fused to the bacterial protein flagellin.

Sixty healthy young volunteers aged 18-49 were randomized to receive the vaccine candidate in dosages of 0.3 μg (6 subjects), 1.0 μg (18 subjects), 3.0 μg (6 subjects), 10 μg (14 subjects), compared to placebo (16 subjects), in two doses injected 28 days apart. Clinical and laboratory safety assessments took place 1 and 7 days after immunization; immune response to M2e and flagellin was assessed at 7, 14 and 28 days after each dose. Seroconversion was defined as a serum IgG anti-M2e antibody (µg/ml) value ≥ 0.174 and a four-fold rise in titer.

The 0.3 and 1.0 µg doses were safe and well tolerated in all subjects and immunogenic in 18 (75%) of 24 vaccinees after the first dose and 23 (96%) after the second dose. In the 1.0 µg group, the geometric mean M2e antibody concentration was 0.4 µg/ml after the first dose and 1.7 µg/ml after the booster dose. Immune responses to flagellin were also robust and did not appear to negatively affect M2e antibody responses from the booster dose. The two highest doses (3 and 10 µg) were associated with the presence of flu-like symptoms in some of the subjects.

Given the strength of the antibody responses and the absence of significant adverse reactions at the two lowest doses (0.3 and 1.0 μg), VaxInnate intends to continue development and clinical evaluation of the vaccine candidate at doses of 1.0 μg and less.

"In this trial, the M2e flu vaccine candidate was well tolerated and able to induce high antibody levels to M2e at 0.3 and 1.0 μg, the two lowest doses we studied," said primary investigator Christine Turley, MD, who is Director of Clinical Trials and Clinical Research at the Sealy Center for Vaccine Development, University of Texas Medical Branch (UTMB). "These results suggest that the M2e vaccine candidate could be a promising and much-needed new option for prevention or attenuation of influenza A disease."

UTMB and VaxInnate researchers are collaborating on a manuscript for submission to a peer-reviewed journal.

The trial was conducted at study sites in Galveston, TX and Lenexa, KS. It was supported by a $9.5 million grant awarded to UTMB by the Bill & Melinda Gates Foundation, for better control of influenza epidemics in the developing world.

Universal Vaccination Challenges

A universal influenza vaccine is one that would provide protection against all strains of seasonal and pandemic influenza A without requiring annual shots. Although universal vaccination has been proposed to improve vaccination coverage and prevent disease, there are no universal vaccines available at this time. Nor is there a means of developing and producing the volume of vaccine necessary to implement universal influenza vaccine recommendations given the inefficiency of current flu vaccine production.

In developing traditional vaccines, epidemiologists must predict months in advance which flu strains will be circulating during the next flu season in order to formulate a vaccine that targets the likeliest candidates. The selected strains are then manufactured in live, fertilized chicken eggs using a laborious process that takes 6 to 9 months.

Federally-funded alternative approaches that are now in development, such as cell-based production, wouldn't reduce the time necessary to produce vaccine and, furthermore, would require construction of large, committed manufacturing facilities.

The inefficiency of egg- or cell-based vaccine production makes it virtually impossible to respond to public health emergencies, such as the emergence of a pandemic avian flu, and impossible to reformulate vaccine if circulating strains do not match those in the vaccine, as was the case during the last flu season.

VaxInnate's Approach and M2e Flu Vaccine Candidate

VaxInnate M2e universal flu vaccine candidate represents a novel approach with respect to both vaccine design and production.

Unlike conventional flu vaccines, the M2e vaccine candidate targets the ectodomain of the M2 protein (M2e), an ion channel protein found on the surface of influenza A viruses. Because M2e is the most highly conserved surface protein of the virus, VaxInnate's vaccine candidate would eliminate the need for epidemiologists to identify and predict strain variants that emerge from year to year, and design an entirely new vaccine annually, as they must now.

Another key difference is the elimination of eggs or cells for vaccine production. VaxInnate's production technology is instead based upon the expression in recombinant bacteria of relevant influenza virus protein antigens fused to the bacterial protein flagellin. Flagellin interacts with the immune system's toll-like receptors (TLRs), which function in human immune cells as sentries to detect pathogens and mount a general immune defense. This initial defense, in turn, stimulates an adaptive immune response that includes production of pathogen-specific antibodies.

VaxInnate scientists believe that their technology can make it possible to produce flu vaccine of heretofore unseen quality rapidly and inexpensively in volumes sufficient to meet national and global needs in as little as a couple of months. No other vaccine technology in use or in development today has these same potential capabilities.

In addition, VaxInnate's use of bacterial expression for vaccine production doesn't require costly expansion of manufacturing capacity, as do other influenza vaccine products. Due to its efficiency and transferability, VaxInnate's flu vaccine could instead be produced in existing biotechnology facilities with microbial production capacity.

About VaxInnate

VaxInnate is a privately-held biotechnology company in Cranbury, NJ and New Haven, CT that is pioneering breakthrough technology for use in developing novel, proprietary vaccines for seasonal and pandemic influenza. This technology has the potential to dramatically improve the potency, manufacturing capacity and cost-effectiveness of influenza vaccines.

In addition to an hemagglutinin (HA)-flagellin flu vaccine candidate in clinical development at the University of Rochester, VaxInnate is on track both to begin a Phase II study of its M2e universal influenza vaccine candidate and to advance a vaccine candidate for H5 avian influenza virus - the most likely parent of a new pandemic strain -- into clinical development in 2009.

VaxInnate's technology platform is also being investigated for development of vaccines for other diseases. For more information about VaxInnate, please visit http://www.vaxinnate.com.

Better by design: Engineering flu vaccines

Calisha Myers — Thu, 19 Mar 2009 08:26:19 -0400

Better by design: Engineering flu vaccines

New method could improve vaccines for both seasonal flu and bird flu

HOUSTON -- (March 17, 2009) -- A new computerized method of testing could help world health officials better identify flu vaccines that are effective against multiple strains of the disease. Rice University scientists who created the method say tests of data from bird flu and seasonal flu outbreaks suggest their method can better gauge the efficacy of proposed vaccines than can tests used today.

Rice's Michael Deem, the lead scientist on the project, will present the group's results March 19 at the American Physical Society's 2009 meeting in Pittsburgh. The results are also slated to appear in the forthcoming book "Influenza: Molecular Virology" from Horizon Scientific Press.

Avian flu, or bird flu, is a particularly deadly type of flu that's transmitted from birds to humans. It hasn't yet evolved into a form that can be transmitted readily between humans, but scientists and world health authorities are trying to prepare for a potential outbreak. Because the virus mutates continually, creating a vaccine in advance is problematic. For example, scientists have already found that a vaccine designed for the 1997 strain of bird flu does not work against a 2003 strain.

"Current vaccines contain only a single version of a given flu subtype," Deem said. "We wanted to gauge the effectiveness of a vaccine that contained multiple versions of a given subtype."

World health authorities currently test the efficacy of proposed flu vaccines using either ferrets, which can contract the same forms of flu as people, or genetic assays. Rice's new computerized method could be a cheaper and faster alternative.

With the new method, flu virus mutations are assigned numerical scores. Deem, Rice's John W. Cox Professor of Bioengineering and professor of physics and astronomy, and colleagues developed the method so they could assign a number that captured the amount of difference or similarity between strains. The method can also be used to test how effective a vaccine will be against divergent strains. To verify this, the team checked their results against flu vaccine data collected by the World Health Organization from 1971 to 2004.

"For seasonal influenza, we validated our model against observational data compiled by the World Health Organization's Global Influenza Surveillance Network," Deem said. "We also ran tests against bird flu data. We found that multiple-component bird flu vaccines appeared to be helpful in controlling the simultaneous multiple introduction of bird flu strains."

Influenza viruses are like chameleons. They constantly change the patterns on their outer surface to avoid being targeted by antibodies. This rapid mutation rate is the reason seasonal flu vaccines must be changed annually. However, the vaccines sometimes offer less than ideal protection against newly evolved strains. It takes about six months to produce annual vaccine supplies; also, ideal vaccine strains are often difficult to produce by the standard hen's egg technology, and alternative strains are substituted.

"Oftentimes, bird flu seems to emerge with multiple strains, and something similar can happen with newly released or evolved strains of seasonal flu as well," Deem said. The computational approach Deem will discuss is able to estimate the need for and the efficacy of a multiple-component vaccine in the face of the emergence of multiple flu strains.

Each year, world health authorities create a flu vaccine that protects against three types of seasonal flu -- two subtypes of type A flu and one subtype of type B.

Intanza®, the First Intradermal Influenza Vaccine, receives the European Marketing Authorisation

Calisha Myers — Thu, 26 Feb 2009 17:01:55 -0500

Intanza®, the First Intradermal Influenza Vaccine, receives the European Marketing Authorisation

Intanza®, the first seasonal flu vaccine delivered by intradermal microinjection, has been granted a marketing authorisation by the European Commission.

Intanza® is approved for use in adults 60 years of age and older, especially in those who run an increased risk of influenza-associated complications. With ageing, the immune system tends to weaken - older adults become not only more susceptible to infections but also less responsive to vaccination, a phenomenon known as immunosenescence.

The intradermal administration of Intanza® provides a direct and effective access to the immune system through the dermal skin layer, where there is a high concentration of specialised immune cells and extensive vascularized network, leading to a synergistic activation of immune responses. The pre-filled and ready-to-use microinjection system* with a very short needle enables accurate and reliable delivery into the dermis. "We are pleased to offer the elderly and their doctors this new vaccine which should contribute to improve the prevention from an underestimated disease that continues to kill people and to cause serious complications", says Yves Mégard, Director Medical Affairs for adult and senior vaccines at Sanofi Pasteur MSD.

The application for marketing authorisation for Intanza® was supported by the results of clinical trials involving more than 7,000 adults and elderly participants. These trials evaluated the safety and ability to generate an immune response of this novel seasonal influenza vaccine. Intanza® generated a high level of immunity against all tested influenza strains in participants older than 60 years.

Sanofi Pasteur MSD will market Intanza® within Western Europe†. Outside this territory, the vaccine will be marketed by Sanofi Pasteur, one of Sanofi Pasteur MSD's parent companies.

Juvaris BioTherapeutics Announces Positive Data from Clinical Trial of JVRS-100 Adjuvanted Flu Vaccine

Calisha Myers — Thu, 08 Jan 2009 14:46:44 -0500

Juvaris BioTherapeutics Announces Positive Data from Clinical Trial of JVRS-100 Adjuvanted Flu Vaccine

BURLINGAME, Calif.--(BUSINESS WIRE)--Juvaris BioTherapeutics, Inc., a biotechnology company developing adjuvanted vaccines and immunotherapeutics for infectious diseases and cancer, today announced positive results from a Phase 1 clinical trial of its lead compound, JVRS-100, as an adjuvant for influenza vaccines.

Results from the randomized, double blind, controlled trial demonstrated positive effects of the JVRS-100 adjuvant co-administered with a commercial influenza vaccine compared to vaccine alone. Increased antibody responses measured by serum hemagglutination inhibition (HAI) and neutralizing antibody titers were observed in subjects receiving JVRS-100 and vaccine versus vaccine alone in study participants 28 days post-vaccination. HAI and neutralization titers are the accepted correlates of increased protection against illness after exposure to influenza. JVRS-100 administered at the most efficacious dose was well tolerated, with no additional side effects over those associated with influenza vaccine alone. The trial enrolled 128 healthy adult subjects 18 to 49 years of age.

"It is very encouraging to see proof-of-concept in the clinic with this novel adjuvant, and the wide margin of safety indicates that JVRS-100 may be effective as a means to not only improve existing vaccines, but also to develop novel preventative and therapeutic vaccines against diseases for which vaccination has not been possible," said Grant E. Pickering, President and CEO of Juvaris.

"The promising results from this clinical trial indicate that JVRS-100 can increase the immune response generated by existing vaccines without additional toxicity," said Thomas P. Monath, MD, acting chief medical officer at Juvaris. "We look forward to advancing JVRS-100 into Phase 2 clinical development in the elderly patient population and into trials with a pandemic (avian) influenza vaccine. There are profound needs for adjuvants to improve vaccine efficacy, and these study results will accelerate development of other novel vaccines incorporating the JVRS-100 adjuvant to address previously untreatable infectious diseases."

Seasonal influenza affects approximately one billion people worldwide each year and results in 5 million severe illnesses and 500,000 deaths. Approximately 90 percent of the deaths occur in the elderly, where flu infection can lead to severe complications from underlying diseases, pneumonia and death. Seasonal influenza vaccines, which are widely used in the U.S. and developed countries, are effective in only 30 percent of the elderly population. Manufacturers of influenza vaccines are actively pursuing adjuvanted vaccines to improve efficacy and reduce vaccine dosage requirements.

About JVRS-100

JVRS-100 is a cationic lipid-DNA complex that is being developed as an adjuvant to improve the effectiveness of existing vaccines and to develop new vaccines against a variety of infectious diseases. Research indicates that the mechanism of action of JVRS-100 is distinct from other known adjuvants. The adjuvant complex self-assembles with disease-specific antigens and induces substantial antibody- and cell-mediated immune responses, particularly induction of CD4+ and CD8+ T lymphocytes. Immunological responses elicited by the lipid-DNA complexes have been successfully demonstrated in both prophylactic and therapeutic vaccine settings in multiple species. This platform provides the opportunity to develop many disease-specific immunotherapy products for which there are significant unmet medical needs.

About Adjuvants

Adjuvants enhance the immunogenicity of antigens incorporated into vaccines. In addition, adjuvants can accelerate and prolong the immune response to vaccination as well as reduce the amount of antigen required per immunization. Adjuvants provide improved immunity to disease antigens by converting soluble protein antigens into particulates and/or by incorporating microbial constituents, which are able to improve antigen presentation and activation of signaling receptors associated with both the innate and adaptive immune response. Vaccines incorporating antigens alone, particularly inactivated vaccines and new generation vaccines based on recombinant and subunit proteins, are not sufficient to protect against or treat many global infectious diseases. Adjuvants will be critical to facilitate development of new vaccines against current and emerging disease pathogens.

About Juvaris

Juvaris BioTherapeutics is a clinical stage company developing adjuvanted vaccines and immunotherapeutics to treat infectious diseases and cancer. The Company's lead product candidate, JVRS-100, is currently in clinical development as an adjuvant to improve the efficacy of seasonal influenza vaccines in the elderly population. The Company is also developing proprietary vaccines for HSV-2, universal flu and pandemic flu and is initiating clinical development of an immunotherapeutic to treat acute leukemia with grant funding from a leading academic institution. Juvaris completed a Series A financing led by Kleiner Perkins Caufield & Byers and has been awarded multiple NIH grants. More information about the Company and its technology can be obtained at its website: www.juvaris.com.

Baxter Receives EMEA Positive Opinion for CELVAPAN, The First Cell Culture-Based Pandemic Flu Vaccine

Calisha Myers — Tue, 23 Dec 2008 14:51:55 -0500

Baxter Receives EMEA Positive Opinion for CELVAPAN, The First Cell Culture-Based Pandemic Flu Vaccine

Clinical data from a Phase III and subsequent booster study demonstrate safety, immune response and cross-protective memory

DEERFIELD, Ill.--(BUSINESS WIRE)--Baxter International Inc. (NYSE: BAX) today announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMEA) has issued a positive opinion for the marketing authorization of CELVAPAN, the first cell culture-based H5N1 (avian flu) pandemic vaccine, in the European Union.

The positive opinion precedes the licensure of the "mock-up" vaccine, which allows CELVAPAN to be used if the World Health Organization (WHO) officially declares a pandemic. The positive opinion was based on results from a comprehensive clinical development program, including a Phase III clinical trial that demonstrated vaccines for two different H5N1 virus strains were well tolerated and generated a functional immune response.

"We are very pleased to receive the EMEA's positive opinion for CELVAPAN," said Hartmut Ehrlich, M.D., vice president, BioScience global research and development. "This is another step towards our goal of supplying a safe and effective vaccine to protect the population against a possible influenza pandemic."

A "mock up" vaccine is identical to the future pandemic vaccine in composition and manufacturing; however, since the actual pandemic strain is not known, the vaccine contains another influenza strain not yet exposed to the general population. Once a pandemic is declared, this licensure allows for a fast track approval of the vaccine containing the actual pandemic strain.

CELVAPAN is made using Baxter's proprietary Vero cell technology, which offers advantages against conventional egg-based vaccine technology. Baxter's Vero cell manufacturing process is more rapid due to its ability to use the "native" virus that does not need to be modified in order to grow in chicken eggs. The shorter time for vaccine production is critical in accelerating vaccine supply in response to an influenza pandemic.

CELVAPAN is produced in Bohumil, Czech Republic, at one of the largest cell culture vaccine production facilities in the world. Vero cell technology uses a well-established continuous mammalian cell line to produce the pandemic vaccine.

Baxter's candidate avian flu vaccine is derived from the H5N1 strain A/Vietnam/1203/2004. Its antigen composition and structure are identical to the actual virus circulating in nature. This vaccine formulation alleviates the need to enhance the immune response by including adjuvants (additives) that may cause side effects. In the Phase III study, CELVAPAN induced an immune response that is similar to the body's defense against a natural influenza virus infection.

Phase III Clinical Trial Results

The purpose of the randomized Phase III study was to evaluate safety and immune responses to 7.5 µg of the Vietnam strain vaccine in two age groups (adults 18-59 and elderly, i.e., older than 60). The antibody persistence and immune response to a booster with either the same or a different strain was also measured. The study also investigated the ability of the vaccine to induce cross-immunity against divergent H5N1 strains.

Overall, the vaccine was well tolerated after the first and second vaccination as well as after the booster, with a safety profile similar to currently licensed seasonal influenza vaccines. The most common side effects were injection site pain and headache, fatigue or malaise.

A positive immune response was induced even after only one immunization as determined by measurement of functional antibodies using a microneutralization assay (50.7 percent in the adult group; 54.4 percent in the elderly group). Following the second immunization, 73 percent of subjects in the adult and 74 percent in the elderly age group demonstrated seroneutralizing levels of antibody, meaning the vaccine was found to be at least equally immunogenic in the elderly as in the adult age group. A six-month booster vaccination with either A/Vietnam/1203/2004 or A/Indonesia/05/2005 strain vaccines induced a substantial booster response. A booster vaccination using a different strain resulted in high levels of antibodies against the initial and the booster strain, which is indicative of cross-protective immunological memory.

Last June, The New England Journal of Medicine published data demonstrating CELVAPAN met Phase I/II trial endpoints for safety and immunogenicity (generating a functional immune response). This was the first peer-reviewed publication of study results for CELVAPAN, the first cell culture-derived avian influenza vaccine to undergo clinical evaluation.

About Pandemic Flu

A pandemic is a global disease outbreak caused by an agent for which there is little or no immunity in the human population and which can spread easily from person-to-person worldwide causing serious illness and death. Most cases of avian flu infection in humans have so far resulted from direct or close contact with infected poultry (e.g., domesticated chicken, ducks, and turkeys) or surfaces possibly contaminated from feces of infected birds. Avian influenza infection follows an unusually aggressive clinical course, with rapid deterioration and a high fatality rate.

About Baxter

Baxter International Inc. develops, manufactures and markets products that save and sustain the lives of people with hemophilia, immune disorders, infectious diseases, kidney disease, trauma, and other chronic and acute medical conditions. As a global, diversified healthcare company, Baxter applies a unique combination of expertise in medical devices, pharmaceuticals and biotechnology to create products that advance patient care worldwide.

SDI Reports: Number of Flu Vaccines Given in Physicians' Offices Lower This Season

Calisha Myers — Mon, 15 Dec 2008 09:46:22 -0500

SDI Reports: Number of Flu Vaccines Given in Physicians' Offices Lower This Season

The Number of Vaccines Given After Thanksgiving Has Not Rebounded

December 15, 2008

PLYMOUTH MEETING, Pa.--(BUSINESS WIRE)--Despite recommendations from the CDC's Advisory Committee on Immunization Practices (ACIP) that healthcare providers encourage influenza vaccination throughout the flu season, the number of flu vaccines given in physicians' offices is lower at this point in the 2008-2009 season than in the previous two seasons, according to SDI's VaccineTrackTM. The flu season typically begins in the fall and does not peak until January or February most years.

SDI's VaccineTrackTM provides weekly tracking of vaccine administration in physicians' offices based on nationally projected data from electronic office medical claims. VaccineTrackTM reports current utilization of injectable flu vaccine by patient and provider demographics including medical specialty, patient age range and gender. Encounters can also be segmented by whether vaccine recipients fall into high health risk versus no health risk categories.

Data from VaccineTrackTM to date for the 2008-2009 season also shows that the number of flu vaccines given in physician offices has not rebounded after Thanksgiving as it has the past two seasons.

SDI maintains the largest influenza monitoring program in the United States and has tracked, measured, and forecasted the number of people affected by cough, cold, influenza and other upper respiratory conditions to assist clients and consumers alike for over 25 years.

About SDI

Since 1982, SDI has been delivering innovative healthcare data products and analytic services to the pharmaceutical, biotech, healthcare, medical device, financial services, and consumer packaged goods industries. SDI is the leading provider of de-identified patient-level data analytics and offers a broad array of solutions and insights across the continuum of care. These include custom and syndicated patient-level data studies; localized disease and treatment surveillance and projection; market research audits; healthcare profiles; comprehensive managed care offerings; clinical trial optimization; direct-to-patient pharmacy programs; marketing effectiveness; sales targeting and compensation products; data integration, warehousing, and mining; list services; and direct marketing services. Its current roster includes the top 50 pharmaceutical/biotech companies. For more information, visit www.sdihealth.com or call 610.834.0800.

GSK Major Seasonal Influenza Vaccine Efficacy Trial To Assess Superior Protection For Those At Risk Of Influenza

Calisha Myers — Mon, 10 Nov 2008 14:32:49 -0500

GSK Major Seasonal Influenza Vaccine Efficacy Trial To Assess Superior Protection For Those At Risk Of Influenza

GlaxoSmithKline (GSK) announced today that it has started a worldwide clinical efficacy trial to evaluate an innovative vaccine for the prevention of seasonal influenza. The trial is one of the largest influenza efficacy trials ever undertaken for seasonal flu. Over 43,000 volunteers are expected to be enrolled in the phase III clinical trial.

"With this large clinical trial in seasonal influenza, we are building on the leading role GlaxoSmithKline Biologicals has already played in the development of pandemic protection. This new seasonal vaccine contains an adjuvant similar to the one pioneered for the only influenza pre-pandemic vaccine approved in Europe, PrepandrixTM, and the pandemic vaccine PandemrixTM," said Jean Stéphenne, President and General Manager GSK Biologicals. "We are looking to develop a superior influenza vaccine that will provide those at risk of influenza with better protection."

The multicenter Phase III study is an observer-blind, randomized, efficacy study. Subjects will be randomized to receive a single dose of the new vaccine or a currently available vaccine each year of the two year trial. The study population will comprise adults aged 65 and older at the time of vaccination.

The trial involves over 43,000 volunteers and will take place in 15 countries, including Belgium, Czech Republic, Estonia, France, Germany, United Kingdom, Netherlands, Norway, Poland, Romania, Russia, Taiwan, Mexico, United States, and Canada.

In clinical trials to date with the influenza vaccine GSK2186877A the side effects seen were mild-to-moderate, of short duration and are common to flu vaccines. The most common were injection site pain, redness, swelling and itching at the injection site, fatigue (tiredness), muscle pain, joint pain, headache, nausea and chills/shivering.

About GlaxoSmithKline (GSK)

GSK - one of the world's leading research-based pharmaceutical and healthcare companies - is committed to improving the quality of human life by enabling people to do more, feel better and live longer. For company information, visit GlaxoSmithKline at http://www.gsk.com.

About GlaxoSmithKline Biologicals (GSK Bio)

GlaxoSmithKline Biologicals (GSK Biologicals) is a global vaccine company which has shown itself to be a leader in innovation. The company is active in the fields of vaccine research, development and production with over 30 vaccines approved for marketing and 20 more in development. Headquartered in Belgium, GSK Biologicals has 14 manufacturing sites strategically positioned around the globe. In 2007 GSK Biologicals distributed 1.1 billion doses of vaccines to 169 countries in both developed and the developing world - an average of 3 million doses a day.

GSK Biologicals employs over 9 000 people worldwide including more than 1 600 passionate scientists engaged in research aimed at discovering innovative vaccines that contribute to the health and well-being of people of all generations around the world. http://www.gsk-bio.com/english/index.html

PrepandrixTM and PandemrixTM are trade marks of the GlaxoSmithKline group of companies.

Pneumococcal Vaccine Could Prevent Numerous Deaths, Save Costs During A Flu Pandemic, Model Predicts

Calisha Myers — Thu, 06 Nov 2008 09:18:54 -0500

Pneumococcal Vaccine Could Prevent Numerous Deaths, Save Costs During A Flu Pandemic, Model Predicts

(Oct. 31, 2008) - A new predictive model shows that vaccinating infants with 7 valent pneumococcal conjugate vaccine (PCV7)--the current recommendation--not only saves lives and money during a normal flu season by preventing related bacterial infections; it also would prevent more than 357,000 deaths during an influenza pandemic, while saving $7 billion in costs.

Keith P. Klugman, PhD, professor of global health at Emory University's Rollins School of Public Health, will present results of the research using the predictive model at the joint ICAAC/IDSA meeting in Washington, DC, Oct. 25-28. (Interscience Conference on Antimicrobial Agents and Chemotherapy/Infectious Disease Society of America.)

Bacterial infections, particularly pneumococcal disease, can follow a viral illness such as flu and cause secondary infections that worsen flu symptoms and increase influenza-related risk. Bacterial infections may have been the cause of nearly half of the deaths of young soldiers during the 1918 flu pandemic.

"We've known for years that bacterial infections can develop after influenza," says Klugman. "Unlike the 1918 flu pandemic, which preceded the antibiotic era, we now have vaccines that can prevent these types of pneumococcal infections. This model shows what a dramatically different outcome we could expect with standard PCV vaccination."

Klugman and colleagues at Harvard University, i3 Innovus in Medford, Ma. and Wyeth Research constructed a model to estimate the public health and economic impact of current pneumococcal vaccination practices in the context of an influenza pandemic.

Since 2000 the Centers for Disease Control and Prevention (CDC) Immunization Practices Advisory Committee (ACIP) has been recommending PCV vaccinations for infants and children.

The new predictive model was used to compare the results of no PCV vaccination to the current routine vaccination of infants less than two years old. The researchers assessed the effect of vaccination policies under both normal and pandemic influenza conditions. They included both direct vaccination effects in vaccinated individuals and indirect vaccination effects (called herd immunity) in the unvaccinated. For manifestations of pneumococcal disease, they included invasive pneumococcal disease (meningitis or bacteremia), all-cause pneumonia and all-cause acute otitis media (ear infections). The model's estimates were based on the 1918 pandemic.

The new model predicted that current pneumococcal vaccination practices reduce costs in a typical flu season by $1.4 billion and would reduce costs by $7 billion in a pandemic. In a pandemic, they would prevent 1.24 million cases of pneumonia and 357,000 pneumococcal-related deaths.

"Our research shows that routine pneumococcal vaccination is a proactive approach that can greatly reduce the effects of a future flu pandemic," says Klugman. Countries that have not yet implemented a pneumococcal vaccination program may want to consider this as part of their pandemic flu preparedness."

The research was funded by Wyeth Research. Dr. Klugman is a paid consultant for Wyeth Pharmaceuticals.

High dose of flu vaccine boosts immune response in elderly

Calisha Myers — Thu, 30 Oct 2008 09:03:15 -0400

High dose of flu vaccine boosts immune response in elderly

October 26, 2008

Giving people age 65 and older a dose four times larger than the standard flu vaccine boosts the amount of antibodies in their blood to levels considered protective against the flu, more so than the standard flu vaccine does. The findings from a study of nearly 4,000 people were presented Oct. 26 at a national meeting on infectious diseases.

The higher dose of vaccine generally resulted in approximately 30 percent to 80 percent more antibodies against flu, long considered a good measure of protection.

Ann Falsey, M.D., associate professor of medicine at the University of Rochester School of Medicine and Dentistry and an infectious diseases specialist at Rochester General Hospital, presented the results at the 48th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC)/Infectious Diseases Society of America (IDSA) 46th annual meeting. The study was funded by sanofi pasteur, the vaccines division of sanofi-aventis Group, which makes Fluzone® Influenza Virus Vaccine, a licensed flu vaccine used widely in the United States and elsewhere.

The immune system generally weakens as we get older, not only leaving people more vulnerable to infection but also reducing their ability to respond to vaccination. While some studies have questioned the effectiveness of the flu vaccine in older adults, the nation's leading public health experts stress that it's a worthwhile, even life-saving, measure. About 90 percent of the estimated 36,000 people who die from flu-related causes in the United States each year are 65 and older.

"Without doubt, the influenza vaccine as it is today is beneficial for everyone, including older adults, and we strongly encourage every older person, and every person with a chronic illness, to get vaccinated," said Falsey. "However, older people generally don't respond to vaccines as well as young healthy adults and therefore, there is much room for improvement. The goal is to increase immune response in older adults, since this is one of the populations most at risk for becoming seriously ill or dying from influenza."

The conventional flu vaccine is a combination of three circulating strains of flu, with each component consisting of 15 micrograms of material designed to evoke an immune response to protect a person against a particular type of flu. In the study headed by Falsey and conducted at 30 sites around the country in fall 2006, physicians compared the immune response brought about from a traditional flu vaccine compared to that from a vaccine shot containing four times as much material - 60 micrograms of material known as hemagglutinin for each of the three components.

In the study of people age 65 and older, the larger dose was given to 2,575 participants, while 1,262 subjects received the standard dose. Scientists checked the level of antibodies in the blood of the participants one month later. Generally, the large-dose vaccine increased the number of flu antibodies in study participants on average from about 30 to 80 percent. The level of such antibodies in the blood has long been considered a good gauge of how protected people are against the flu.

A greater percentage of people who received the high-dose vaccine had the typical side effects associated with the flu shot, including redness, swelling, and pain at the site of the injection, but the symptoms generally did not last longer than three days.

One especially interesting bit of data from the study, according to Falsey, was the effect of the larger dose on people who had no measurable antibodies against certain strains of the flu when the study began. Such people are considered especially vulnerable because their body doesn't have the "head start" that most people have in generating at least some protection against flu on their own, before the vaccine offers a needed boost. These people might also represent a group that does not respond well to vaccines in general.

Even in this group, the larger dose greatly increased the number of such individuals who ultimately had antibody levels considered protective. For example, 51 percent of such individuals who received the standard dose had an antibody level thought to be protective against one of the strains, H1N1, included in the vaccine, while 74 percent of participants who received the high dose reached the same levels. The percentages also went up for the other two strains included in the shot, from 82 to 96 percent for the H3N2 strain and from 41 to 56 percent for the type B strain.

"These are the people at the highest risk for becoming very sick from influenza, and we saw significant improvement in the immune response in many of these people," said Falsey. "This is very encouraging."

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Among the study participants were 129 in Rochester, N.Y., including 100 people at Rochester General Hospital and 29 people at the University of Rochester Medical Center.

VaxInnate's Second Flu Vaccine Candidate Enters Clinical Development; Results Expected in Early 2009

Calisha Myers — Tue, 30 Sep 2008 10:24:47 -0400

VaxInnate's Second Flu Vaccine Candidate Enters Clinical Development; Results Expected in Early 2009

Study Tests Novel Technology with Potential to Transform Production of Flu Vaccines

CRANBURY, N.J.--(BUSINESS WIRE)--VaxInnate Corporation, a biotechnology company pioneering breakthrough technology to develop novel seasonal and pandemic influenza vaccines, today announced that its second influenza vaccine candidate has entered clinical development.

The Phase I study is expected to yield important information about the safety and immunogenicity - or ability to generate an immune response -- of VaxInnate's hemagglutinin (HA)-flagellin flu vaccine candidate. The study is taking place at the University of Rochester in New York. Results are expected in early 2009.

The HA vaccine candidate links the hemagglutinin (HA) antigen, which has been the key protective component in flu vaccines for many years, to flagellin, a bacterial protein that interacts with the immune system's toll-like receptors (TLRs) to enhance the vaccine candidate's immunological potency. The vaccine candidate is produced by recombinant expression in bacteria using VaxInnate's proprietary manufacturing technology.

"The advance of VaxInnate's second vaccine candidate into clinical development is an important milestone in our comprehensive flu vaccine development program," said CEO Alan Shaw, PhD. "This is a critical first test of our HA vaccine candidate, which has the potential to be a highly effective, less expensive and more efficiently produced alternative to current flu vaccines, whose shortcomings have handicapped our ability to address seasonal and potential pandemic flu."

The open-label, escalating, dose-ranging study includes 56 healthy adult volunteers aged 18-49 years who are receiving a single intramuscular dose ranging from 0.1 ug to 8 ug of vaccine candidate. There will be six months of follow-up after administration of the vaccine candidate.

"We believe VaxInnate's approach to flu vaccine development has a great deal of promise and look forward to learning more about the potential of the HA flu vaccine candidate in this first clinical trial," said John Treanor, MD, primary investigator of the study.

Dr. Treanor, who has a long standing interest in influenza pathogenesis and vaccine development, is also Professor of Medicine and Professor of Microbiology and Immunology at the University of Rochester School of Medicine and Dentistry.

VaxInnate's Approach and the HA Vaccine Candidate

In developing traditional flu vaccines, epidemiologists must predict months in advance which flu strains will be circulating during the next fall/winter season in order to formulate a vaccine that targets the likeliest candidates. That's because hemagglutinin (HA), a vaccine antigen that has been used in flu vaccines for many years, changes over time, in turn forcing manufacturers to change the strains of HA used in seasonal flu vaccines.

The selected flu strains are then manufactured in live, fertilized chicken eggs using a laborious process that takes 6 to 9 months. Federally-funded alternative approaches now in development, such as cell-based production, also take 6 months and require sizable, committed manufacturing facilities for large-scale vaccine production.

Using either of these means of production, the time necessary to produce flu vaccine makes it difficult to respond to public health emergencies, such as the emergence of a pandemic flu, and virtually impossible to reformulate vaccine should circulating strains not match those in the seasonal vaccine, as was the case during the 2007-2008 flu season. Difficulties in growing virus strains have also resulted in vaccine shortages early in flu season, when most vaccination takes place.

Unlike egg- or cell-based vaccine production, VaxInnate's technology is based upon the expression in recombinant bacteria of relevant influenza virus protein antigens - in this case, HA -- fused to the bacterial protein flagellin. Flagellin interacts with the immune system's toll-like receptors (TLRs), which function in human immune cells like sentries to detect pathogens and trigger a general immune defense. This initial defense releases cytokines and other signals that in turn stimulate a second, stronger adaptive immune response, including production of pathogen-specific antibodies.

This new technology could produce highly potent influenza vaccine that can be rapidly and inexpensively produced in volumes sufficient to meet national and global needs, and be suitable for stockpiling.

About VaxInnate

In addition to the HA flu vaccine candidate in clinical development, VaxInnate is on track both to begin a Phase II study of its M2e universal influenza vaccine candidate and to advance a vaccine candidate for H5 avian influenza virus - the most likely parent of a new pandemic strain -- into clinical development in 2009.

Positive findings from a Phase I clinical trial of VaxInnate's universal flu vaccine candidate will be presented at next month's joint Interscience Conference on Antimicrobial Agents and Chemotherapy/Infectious Diseases Society of America (ICAAC/IDSA) meeting in Washington, DC.

VaxInnate's technology platform is also being investigated for development of vaccines for other diseases. For more information about VaxInnate, please visit http://www.vaxinnate.com.