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Vaccines
Influenza Vaccines under development
 Influenza is a highly contagious, acute viral respiratory disease that occurs seasonally in most parts of the world. Epidemics occur annually and are the cause of significant morbidity and mortality worldwide. Influenza disease affects all age groups, with the highest hospitalization rates found in children and the elderly. Influenza results in an average of 220,000 hospitalizations and an average of 36,000 excess deaths annually. Over 90% of influenza-related deaths occur in people over the age of 65. Children under the age of five and women in the third trimester of pregnancy are also at higher risk for serious complications. Recent data also suggests that influenza vaccinations play a role in reduction of heart attacks and stroke in the elderly. Even though vaccination is the most effective means to reduce influenza disease, the licensed vaccines provide only limited sero-conversion in the elderly. Therefore there is a need for a more efficacious vaccine. Datamonitor projects that the influenza market will reach $3.7B by 2010.
 FluBlØk™, or recombinant hemagglutinin (rHA), is a patented subunit influenza vaccine that can replace the current licensed vaccines which are produced in eggs using technology that is more than 60 years old. FluBlØk consists of three rHA proteins derived from the flu strains selected by the World Health Organization and the Center for Disease Control for each year's vaccine. These proteins are produced in Protein Sciences patented expresSF+® insect cells and formulated in PBS without preservatives or adjuvants. Clinical trials have shown safety and efficacy in healthy adults and the elderly population:
- Several Phase I and II trials conducted by the National Institute of Allergy and Infectious Diseases (NIAID) involving over 600 subjects demonstrated safety and efficacy as reported in four studies published in the Journal of Infectious Diseases.
- A Phase II(b) trial conducted by NIAID in 399 elderly subjects was completed in November, 2003. The trial involved three different doses of FluBlØk (containing 15, 45 and 135µg, respectively, of each antigen) compared to the licensed inactivated vaccine (15µg of each antigen). A significantly higher percentage of elderly subjects receiving a higher dose of FluBlØk developed protective antibody titers compared to the licensed vaccine. The results of this study have been published in the Journal of Infectious Diseases. Click here to link to the publication.
- A Phase II/III trial conducted by Protein Sciences in 460 healthy adults was completed during the 2004/05 influenza season. The trial was conducted at three sites in the United States and subjects received one of the two different doses of FluBlØk™ or placebo. The higher dose of FluBlØk, which has been chosen as the commercial dose, showed 100% protective efficacy against laboratory confirmed influenza. FluBlØk also achieved a 54% reduction of CDC-defined influenza-like illness. Subjects were protected not only against the influenza strains contained in the vaccine but also against circulating strains that had changed (drifted); these drifted strains were significantly different (as defined by the CDC) from those in the vaccine. The results of this study have been submitted for publication.
- In October 2005 the FDA advised Protein Sciences that FluBlØk could qualify for the "accelerated approval" mechanism.
- A Phase I/II Pediatric dose-ranging study and Phase III elderly field study commenced in October 2006 to support a 2007 Q4 BLA submission. The Phase III study included 869 subjects over the age of 65. The Phase I/II study included 156 subjects from ages 6 - 59 months. Study completion expected in Q2 of 2007.
Pandemic versions of FluBlØk have been developed from rHA cloned from highly pathogenic avian H5N1 strains. Pandemic FluBlØk has been tested in humans and animals as a vaccine for the potential "bird flu" pandemic influenza threat.
- Pandemic FluBlØk achieved protective titers in 52% of subjects who received two 90µg doses of the vaccine. The results of this study have been published in the Journal of Virology.
- In 1998, the United States Department of Agriculture conducted challenge studies of Protein Sciences H5N1 pandemic FluBlØk in chickens. The high dose of FluBlØk showed 100% protective efficacy in chickens. Not one chicken that received the highest dose of the vaccine became ill or died after being challenged with the lethal virus. Furthermore, no FluBlØk vaccinated chicken was able to shed the virus, which is a critical parameter of an effective pandemic vaccine. The results of this study have been published in the Journal of Infectious Diseases.
- Animal studies conducted by Katz et al. (CDC) indicate that when combined with an approved adjuvant (Alum) a single dose of FluBlØk might be sufficient for pandemic protection.
Recombinant neuraminidase (rNA) has potential for use as an efficacy-enhancing additive to influenza vaccines. rNA has completed Phase II(b) challenge studies conducted by NIAID. Clinical data demonstrated safety and, when combined with the current vaccine, a significant increase in the level of antibodies. Clinical data also showed that for vaccinated people who become ill there was less viral shedding, less severe and shorter duration of illness compared to the licensed vaccine alone.
Our influenza U.S. intellectual portfolio consists of the following published patents:
- USP 5,762,939 Influenza hemagglutinin
- USP 5,858,368 Influenza hemagglutinin
- USP 6,245,532 Signal sequence
- USP 5,976,552 Anti influenza vaccine
- USP 6,103,526 Serum-free cell line
- USP 6,485,729 Neuraminidase supplemented compositions and foreign counterparts
SARS Vaccine
SARS is a respiratory disease caused by a coronavirus. Main symptoms include fever, cough, shortness of breath and difficulty breathing. WHO estimates that SARS is fatal in approximately 10-15% of cases. As of July 31, 2004, 8,096 cases were identified worldwide and 774 people died (Source: World Health Organization).
Coronaviruses infect a variety of livestock, poultry and companion animals. Coronaviruses are spherical, enveloped viruses, ranging from 160-180 nm in diameter and containing a positive-stranded RNA genome. With their genome of approximately 30,000 bases, they are considered the largest of the RNA viruses known. Like influenza viruses they have the ability to genetically recombine with other members of the coronavirus family. Coronavirus is infamous for being a cause of the common cold.
Most research has focused on the Spike protein as a candidate antigen for coronavirus vaccines since it induces virus neutralizing antibodies.
Protein Sciences was awarded a $2.7M grant by NIAID to produce 2,000 doses of a recombinant Spike-protein sub-unit vaccine. Immunogenicity and dose response studies conducted in 2004/05 in mice showed that the recombinant Spike-protein sub-unit vaccine elicited SARS virus neutralizing antibodies in a dose dependant manner. Expanded animal studies to support an IND filing are underway and the SARS vaccine is expected to be tested in human clinical trials in 2006/07.
Click here to view our ICAAC poster on the Development of a SARS Recombinant CoV Spike Protein Vaccine.
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