Media Backgrounder
$25,000 Manning Award of Distinction Sponsored by CanWest Global Communications Inc.
Dr. Harold Jennings, Conjugate Vaccine for Group C Meningitis.
As a boy, Dr. Harold Jennings loved to mix the substances in his home chemistry set and watch, fascinated by the often-unpredictable results. When he became a chemist, his fondness for tinkering with molecules led him to develop a vaccine that is saving hundreds of children's lives each year.
Jennings started working at the National Research Council of Canada in 1966. He quickly earned an international reputation for what other scientists call his "encyclopedic" work in detailing the structures and functions of polysaccharides — purified complex sugars used in industrial processes.
One day, Jennings happened to meet Dr. Emil Gotschlich of Rockefeller University in New York. Gotschlich told him about how there was no effective vaccine to protect infants against meningitis, caused by bacteria whose surface is covered by proteins and complex sugars.
"He got me thinking about how I could apply my expertise to the problem," Jennings says.
Meningitis is caused by bacteria that live in the back of the nose and throat. Many people are carriers of the meningococci bacteria, but their bodies have built up immunity against the bug. In people with no antibodies, however, one to two out of every 100,000 exposed to the bacteria develop a serious illness such as meningitis, an infection of the fluid and lining of the brain and spinal cord.
"It's a terrible disease," Jennings says. "It can kill within 24 hours" if not treated with antibiotics.
Between 250 to 750 cases of meningococcal disease occur every year in Canada, according to the Meningitis Research Foundation of Canada. About one in 20 people infected with meningitis die, while others suffer severe after-effects, including mental retardation, hearing loss and loss of limbs.
Polysaccharide vaccines against meningitis were in use nearly 25 years ago, when Jennings first heard about their ineffectiveness in infants. These vaccines are made of purified complex sugars extracted from the surface of the bacteria that cause various types of meningitis. The vaccine for Group C had proved very successful in containing outbreaks of the disease in older children and adults.
However, because the Group C polysaccharides vaccine derived from the complex sugars contains no protein, it doesn't stimulate the immature immune system in infants. "And about 50 per cent of all cases of Group C meningitis are in infants under two and one-half years old," Jennings notes.
Another problem is that, even in older children and adults, antibodies stimulated by the polysaccharides vaccine diminish with time, so this vaccine "doesn't produce long-lasting immunity."
Jennings knew that vaccines using proteins as a delivery mechanism did — and still do — protect infants against diseases such as diphtheria, tetanus and pertussis (whooping cough).
He and his research team were among the first in the world, in 1978, to try to develop a technique to "conjugate" or chemically link the polysaccharides derived from the meningitis bacteria with a protein. Such a vaccine, he reasoned, should work in everyone — including infants.
"The key to the whole thing was finding a coupling procedure," Jennings says. The technique had to successfully link the complex sugars with the protein in a safe and effective vaccine.
The vaccine also had to be soluble, so each dose could be precisely measured, dissolved in solution for injection, and well tolerated by infants.
Jennings and his team overcame all the hurdles. In 1982, they received the world's first patent on a conjugate Group C vaccine for meningitis.
"The remarkable achievement of producing a novel conjugate vaccine against Group C meningococcal meningitis effective in infants is a major advance in public health," says Rockefeller University's Gotschlich.
Jennings recalls the excitement when he tried his new conjugate vaccine in laboratory mice. The mouse immune response — like that of infants — isn't stimulated when the rodents are given the polysaccharides vaccine made only from the bacteria's complex sugars.
However, when Jennings and his team injected the mice with the novel combined polysaccharides-protein Group C vaccine, the rodents produced high levels of antibodies against the meningitis bacteria. Most importantly, this immune response could be boosted by giving follow-up shots consisting of only the conventional polysaccharides vaccine.
This means the first injection with the conjugate vaccine actually developed what's called the immunologic "memory," Jennings explains. It is the ability of the body's disease-fighting T-cells to "leap to the defence" once the immune system has been exposed to a disease-causing organism.
But it would take Jennings 20 frustrating years to bring the product to market.
Until recent years, the National Research Council required its innovations to be marketed by Canadian companies. But in the 1980s, there was only one vaccine company in Canada. And, after initially expressing enthusiasm for Jennings' new conjugate vaccine, they lost interest.
"If I wanted this technology to survive, I had to go out and do it myself," he recalls. "And I was so enthusiastic about it and I knew the potential, that I started going out and 'selling' it."
Eventually, Jennings met Francesco Bellini, who started the Montreal-based biotech firm BioChem Pharma. Bellini invested in the vaccine's development and co-founded a company, North American Vaccine (NAVA), to bring conjugate vaccines to the market. NAVA was bought by Baxter International Inc., which now sells the NeisVac-C® conjugate Group C vaccine around the world.
In 2000 in the U.K., public health officials used the vaccine to reduce the incidence of meningococcal disease by up to 85 per cent across all age groups compared with the previous year.
Jennings next turned his tinkering to Group B meningitis, for which there is no effective vaccine. He first modified the complex sugars covering the bacteria and then linked them with a protein. The result: a new conjugate Group B vaccine that stimulated the immune response in laboratory animals. The new vaccine, which should also be effective against a similar type of meningitis called E.coli K1 — which is fatal in premature infants — is now undergoing first-phase clinical trials.
Randal Chase, President of Shire Biologics in Laval, Que., says Jennings' vaccines are "the result of years of work and innovative thinking," and make possible "a new generation of vaccines."
In fact, some cancer cells are also covered in the same kind of polysaccharides as Group B meningitis bacteria. Jennings' newest project is to see if he can chemically modify the surface of cancer cells to make them vulnerable to attack by the body's immune system.
Jennings, now 71 and close to retirement, says receiving the Manning Award of Distinction for his life's work recognizes the best thing that can happen to a scientist. "And that is, you can do work that interests you that results in a discovery that actually saves human lives . . .."
The Ernest C. Manning Awards Foundation
This year, Manning Innovation Awards presents $145,000 in prize money distributed among four leading Canadian innovators, as well as $20,000 among eight Canada-Wide Science Fair winners. Since 1982, the Foundation has awarded over $2.9 million to recognize Canadian innovators.
Media contacts (photos available):
Dr. Harold Jennings
National Research Council of Canada
Phone: (613)-990-0821
Email: harry.jennings@nrc.ca
National Research Council of Canada
Phone: (613)-990-0821
Email: harry.jennings@nrc.ca
Donald Park, Executive Director
Ernest C. Manning Awards Foundation
Phone: (403)-645-8288
Website: www.manningawards.ca
Ernest C. Manning Awards Foundation
Phone: (403)-645-8288
Website: www.manningawards.ca