NIH Programs Officer Spreads Word about Influenza Vaccines

To conclude the Natural Sciences and Mathematics Colloquium (NS&M) series for the Fall 2010 semester, Frederick Cassels, ‘80, Programs Officer of the Respiratory Diseases Branch (RDB) of the National Institute of Health (NIH), presented on the development of vaccines for influenza virus and the 2009 outbreak in his presentation Influenza Vaccines and the 2009 H1N1 Experience on Wednesday.

Beginning the final lecture of the series in the Schaefer Hall lecture room at 4:30 p.m., Cassels began his presentation with a background of his time at St. Mary’s, including his transition from studying Maryland Blue Crabs to studying viruses and vaccines.

After graduating from the College in 1980, Cassels took on a biotechnology job for over two years before returning to academics, earning his Ph. D by studying Maryland Blue Crab biochemistry before re-entering the biotechnology field.

“I come back to the College every few years for alumni reunions,” said Cassels. “The last time I presented in front of a St. Mary’s professor, I was a senior, and [Professor of Biology] Bob Paul took us to upstate New York…and I presented there. Most professors would ask a softball question, to get your confidence up…not Bob Paul…and I’m grateful for it now, but not at the time.”

After earning his graduate degree, Cassels took a stronger interest in biochemistry and immunology, moving into molecular-focused virology labs at NIH before settling in his current position as Program Officer of RDB. RDB is a part of the Division of Microbiology and Infectious Diseases in Bethesda, MD, and that division is, in turn, part of the National Institute of Allergy and Infectious Diseases (NIAID) of NIH.

After an introduction of his work at NIH and funding allocations of the NIAID, Cassels discussed the stages of vaccine testing and licensure, a process that can cost up to $100 million and take anywhere from 10 to 20 years to finalize.

He reviewed the four major stages: discovery, indicating the first lab tests and procedures done to indicate a potential vaccine; target ID validation, further identification and processing to determine possible application to animal models; preclinical development involving possibilities of long-term purification but focusing on further testing; and clinical development, during which human tests are performed to verify the vaccine’s effects on the body and, most notably, its triggered immune response.

Cassels next discussed the mass production of the yearly FluBlok® vaccine, produced by the Protein Sciences Corporation. Insect cells are grown in a 500-L bioreactor, and infected with the virus of interest.

Two to three days after infection, when the cells should be expressing the proteins encoded by the viral genome, the cells are purified to obtain ingredients for the vaccine. The process usually results in 90% of pure product, and two-story, 6,000-L bioreactors produce millions of vaccines in a small number of runs.

“Influenza is an upper, and sometimes lower, respiratory infection in humans,” said Cassels, beginning his discussion of the flu virus. “[It causes] quite a few deaths globally, almost 500,000 per year…with an ever-present threat of pandemic in the U.S.”

The virus itself, composed of eight genes, produces proteins related to its basic survival needs: entry into the cell by binding to cell surface receptors (essentially, how one needs a house key to enter a house), replication (copying itself), and viral assembly (building the protein case, or capsid, surrounding the eight viral genes), and cellular release.

The target of the vaccine is hemagglutinin (denoted HA), a type of surface protein on the virus that allows the viral particle to bind to receptors on the cell surface for entry. The vaccine induces the body’s immune response to produce antibodies, small protein units that bind to these receptors and prevent the virus from entering a cell.

While the concept seems simplistic, it is complicated by the mutation rate of the virus, which has led evolutionarily to fifteen forms of HA and mutations of each form from year-to-year, mutations that make previous antibodies (and, therefore, vaccines) ineffective against novel virus strains.

To make vaccine selection more difficult each year, combinations of viruses can also occur within hosts to create a completely new strain, a process called genetic shift. “If an animal is infected with two viruses, those genes can mix,” said Cassels. “And when they do, they can form new molecules.”

Cassels continued with a discussion of flu pandemics in the world’s history, including the Spanish Flu of 1918, the Asian Flu of 1957, the 1968 Hong Kong Flu, and the 1977 Russian Flu.

To combat yearly infections of the influenza virus, two types of vaccines are currently on the market: the trivalent inactivated vaccine (TIV) and the live attenuated vaccine (LIAV).

TIV vaccination involves an intramuscular injection of heat-killed virus particles that induce an immune response in the host to help to fight later live strains.

LIAV vaccinations use a nasal spray to administer live, but weakened, forms of the flu virus that the immune system can, fight to gain a stronger resistance than is provided by TIV. However, this can be more dangerous.

Three viral strains are usually chosen for the vaccine each year: two influenza type A strains, and one influenza type B. Viruses are selected for the vaccine between January and May, are FDA tested and licensed in June and July, packaged in August, released in September, and offered to patients in October and November of the flu season.

The World Health Organization, Food and Drug Administration, Health and Human Services, Centers for Disease Control and Prevention, and NIH, all playing a role in vaccine development each year, were forced to accelerate this process during the 2009 H1N1 outbreak in March.

Cassels concluded his talk with a discussion of the 2009 Influenza strain, its tests that led to the one-dose, 15-microgram vaccine, and the weakened seed strains of that year’s vaccine, which is what lead to the vaccine’s reduced prevention and associated outbreak.

While this talk marked the last of the NS&M Colloquium lectures this semester, the series will resume in Spring 2011.

“I felt that the presentation contained a lot of good information. It was simple to understand, and covered a wide range of information,” said Elliot Russell, a student who attended the lecture. “Some of the information in regards to the budget seemed slightly unneeded, but on the whole, I found the talk informative and am glad I attended it.”

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