MSU study targets safer vaccines for often-fatal whooping cough

Contact: Phil Hearn

(Left) Nara Gavini, Mary Hetrick, and Lakshmi Pulakat
(Left) Nara Gavini, Mary Hetrick, and Lakshmi Pulakat

STARKVILLE, Miss.--A pair of Mississippi State biological scientists are conducting potentially life-saving research that may result in the development of safer whooping cough vaccines, which sometimes lead to brain damage and death.

University professors Lakshmi Pulakat and Nara Gavini are heading a research team that has discovered a unique mechanism in existing vaccines that may trigger neurological damage among whooping cough patients.

"Our research has unraveled a new physiological and biochemical role for a protein whose exact role in neuronal functions is still unclear," said Gavini, former head of the MSU biological sciences department, who now serves on a temporary basis as a program director for the National Science Foundation.

Their findings were presented by MSU research team member and biological sciences doctoral student Mary Hetrick during the recent 106th general meeting of the American Society for Micribiology in Orlando, Fla.

The ASM communications committee and the 2006 ASM general meeting program committee (including biotechnology entrepreneurs and representatives of pharmaceutical companies) highlighted the MSU research because of its potential for the development of safer whooping cough vaccines, according to Pulakat.

Whooping cough--also known as pertussis--is a highly contagious disease affecting about 30-50 million people worldwide, and causing more than 300,000 deaths a year. Children under 1 year are most vulnerable victims and 90 percent of all cases occur in developing countries.

"Neurological damage is a dangerous after-effect among patients suffering from whooping cough, and also seems to affect infants vaccinated with DPT vaccine or acellular vaccine," said Hetrick.

The disease is caused by the bacterium Bordetella pertussis, which produces many toxins upon infection, she explained. Both whole-cell pertussis vaccines and acellular vaccines are used to prevent whooping cough in the United States and other countries.

Whole-cell pertussis vaccines are made from dead bacteria and are used as one of the components of the DPT vaccine--a mixture of three vaccines used to immunize against pertussis, diphtheria and tetanus.

Although severe problems closely following DPT immunization happen very rarely, experts say, those problems may include a serious allergic reaction, prolonged seizures, a decrease in consciousness, lasting brain disease and even death.

"Though the percentage of infants who succumb to the dangerous after-effect among vaccinated populations is small, the public has remained highly concerned regarding the safety of pertussis vaccine," Hetrick said in her research paper.

Acellular vaccine is composed of only those fragments of bacterial cells that are best suited to stimulating a strong immune response. They are genetically engineered S1 subunit protein (promoters) of pertussis toxin that has lost toxicity.

Pulakat, an MSU biology professor, said a two-fold impact of the study on the fields of science and medicine include providing a "strategy to develop a safer vaccine to control whooping cough" and changing "the way biochemists interpret their results when they use S1 subunit as a tool to study cellular signaling."

Hetrick said Pulakat and Gavini "have identified a novel mechanism by which the pertussis toxin can exert its ill effects and contribute to brain damage.

"Since this mechanism is significantly different from the conventional understanding of the action of pertussis toxin, this study provides new possibilities to generate safer acellular vaccines to combat whopping cough," she added.

The research work was initiated by the Pulakat-Gavini team when they were at Bowling Green (Ohio) State University. It stemmed from a National Institutes of Health-funded study to determine the role of a protein implicated in pre-natal and post-natal neuronal development in mammals, including humans.

Hetrick joined the researchers when they were at BSGU and moved to MSU in 2005.

NEWS EDITORS/DIRECTORS: For more information, contact Dr. Pulakat at 662-325-0936 or pulakat@biology.msstate.edu.

For more information about Mississippi State University, see http://www.msstate.edu/.