Saint Louis University researchers are attacking influenza on multiple fronts as they search for a universal vaccine that protects people from the flu virus that often mutates year to year with deadly consequences.
Their progress, as well as the efforts of other researchers in SLU's Center for Vaccine Development who are working to protect people from different infectious diseases, is chronicled in the July/August issue of Missouri Medicine, which focuses on vaccine research.
"As evidenced by the current Ebola outbreak, there are no other potential world health problems that threaten massive death and illness as much as infectious diseases. Some of medicine's greatest triumphs have been in the field of vaccine development," said John C. Hagan III, M.D., editor of Missouri Medicine.
"As an internationally known research facility it was natural for Missouri Medicine: The Journal of the Missouri State Medicine to invite the Center for Vaccine Development at Saint Louis University Medical Center to prepare the theme scientific articles for our July/August 2014 issue."
Formed at SLU 25 years ago and continuously funded by the National Institutes of Health, the Center of Vaccine Development has been instrumental in developing numerous vaccines that protect public health including the FLUMist nasal spray influenza vaccine and vaccines against smallpox and other potential biological weapons post 9/11. The Center for Vaccine Development also was one of the leaders on national research into an H1N1 influenza vaccine, used to protect people from the pandemic that swept the nation in 2009.
Through the years, scientists at the center also have worked on vaccines for tuberculosis, herpes simplex, hepatitis C, Dengue, pneumonia, meningitis and pertussis. They have conducted more than 100 clinical trials that have enrolled about 7,000 community volunteers.
During the last quarter century, their work has received more than $150 million in funding from various NIH contracts and grants as well as funding from multinational foundations. SLU's Center for Vaccine Development expects to receive an additional $50 to $75 million by 2023 from its recent contract as a federally funded Vaccine and Treatment Evaluation Unit (VTEU).
In the July/August issue of Missouri Medicine, SLU researchers described their work to prevent several serious infectious diseases. Here is a link to their articles.
Influenza: Thousands of U.S. residents - typically those who are elderly, young children and pregnant women -- die of complications of the flu every year. In addition, an influenza pandemic hits middle-aged and younger adults harder than those of other ages.
"Influenza remains a major problem causing significant illness and death annually. In addition, periodic pandemics present the potential for 10 to 100 fold increased mortality," write Daniel Hoft, M.D., Ph.D., director of the division of infectious diseases, allergy and immunology at SLU, and Robert Belshe, M.D., director of SLU's Center for Vaccine Development. "The Saint Louis University Center for Vaccine Development is highly engaged in multiple efforts to generate universally relevant influenza vaccines."
The Center for Vaccine Development is working on several types of flu vaccines. For instance, a two part vaccine potentially primes the body for infection with molecules from one influenza virus and enhances its ability to fight flu by boosting with molecules from a different influenza virus. Another vaccine uses two inactivated parts of a virus that the body had not seen to induce immunity against infection with a new strain of influenza. Vaccines are designed to induce broad antibodies that neutralize the virus. And new vaccines being tested have the potential to marshal infection-fighting T cell proteins into action to battle a new flu strain.
Tuberculosis: The bacteria that causes tuberculosis infects one-third of the world's population and between one and two million people die of complications from tuberculosis each year. The current Bacillus Calmette-Guerin (BCG) tuberculosis vaccine protects most children from death and the most severe complications from TB.
However the vaccine does not reliably prevent TB infection and lung-related TB disease in adults.
"Improved TB vaccines are urgently needed," writes Hoft. "Increasing rates of resistance to drugs that treat TB threaten to render all of our current regimens useless and the HIV pandemic has greatly amplified the risks of TB infection, transmission and disease progression."
Partially backed by the Aeras Foundation, which is supported in part from the Bill & Melinda Gates Foundation, SLU's Center for Vaccine Development has studied several vaccine approaches to protect against TB. These include oral and nasal spray versions of the current BCG vaccine, new vaccines that rev up T cells to induce immunity against TB and a vaccine that uses an adenovirus to deliver an antigen causing the body to produce antibodies and T cells that fight TB. In addition, Hoft is researching a new vaccine testing process in hopes of identifying strategies to accelerate the search for new and effective tuberculosis vaccines.
Smallpox: Although smallpox has been eliminated through vaccination, the U.S. government is concerned that the virus that causes the deadly disease could intentionally be used as a bioterror weapon. SLU's Center for Vaccine Development has been on the forefront of smallpox vaccine research.
Sharon Frey, M.D., clinical director of the Center for Vaccine Development, led research published in 2002 that showed the government's store of existing Dryvax smallpox vaccine could be diluted to protect 10 times more people. Since that time, Frey has studied new vaccines for smallpox that appear to offer similar protection to Dryvax, which have been added to the national strategic stockpile of medicines to protect the American public.
"Immunoinformatics and systems biology will provide newer tools for the development of new smallpox vaccines," Frey writes. "Saint Louis University continues to participate in NIH-funded smallpox and other important biodefense vaccine studies."
Dengue: At least half the world's population is at risk for dengue virus, which is spread by the Aedes mosquito. Up to 390 million people worldwide are infected with dengue virus each year, about 100 million develop dengue fever and 22,000 die.
Five dengue vaccines currently are being tested in humans. "Dengue vaccine development has advanced considerably in the past 10 years and it is hoped an effective vaccine will be available soon," writes Sarah George, M.D., assistant professor of infectious diseases, allergy and immunology at SLU. George has conducted two first in-human clinical trials of dengue vaccines at SLU's Center for Vaccine Development.
Barriers to vaccination: Vaccines prevent diseases and deaths, yet some people are not getting recommended vaccinations. Edwin Anderson, M.D., research professor in infectious diseases at SLU, examined how to address the problem.
"The successful prevention of severe infectious diseases by vaccination is without question. Despite this success, there is room for improvement among adults and children," Anderson writes.
While vaccinations have prevented more than 100 million cases of eight contagious diseases, there have been resurgences of measles, rubella, mumps and pertussis - illnesses for which we have vaccines.
Among Anderson's multiple suggestions to improve vaccination rates: physicians must play a key role in dispelling misconceptions parents might have in vaccinating their children and clearly communicate with parents and office medical staff that vaccines should be timed according to published guidelines. In addition, doctors should discuss vaccinations with adult patients to educate them and simplify procedures to make it easier to get vaccines.
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