BUSM/BMC Researcher Receives NIH Grant to Study Gonococcal Vaccine Development

Lee Wetzler, MD, associate program director for research in the section of infectious diseases at Boston University School of Medicine (BUSM) and an attending physician in the section of infectious diseases in the department of medicine at Boston Medical Center, was awarded a four-year, $2.35 million grant from the National Institutes of Health (NIH) to study the development of a gonococcal vaccine. This goal of this work, which is being done in collaboration with Scott Gray-Owen, PhD, at the University of Toronto, is to develop a new model for gonococcal vaccine evaluation and prioritize the feasibility of vaccine candidates to guide future research.

Wetzler, who also is a professor of medicine and associate professor of microbiology at BUSM, has a three-phase plan for developing a gonococcal vaccine. First he will analyze the immune response to vaginal gonococcal infection in laboratory models. The second phase is to determine whether infection with live or killed organisms will provide any protection in this model. The final phase is the evaluation of several vaccine candidates consisting of several bacterial outer membrane antigens.

For the past 30 years, researchers have unsuccessfully been working on the development of a gonococcal vaccine. Increasing antibiotic resistance has made the development of a vaccine for this disease vital and now urgent. The Centers for Disease Control now recommends only one class of antibiotics to treat gonorrhea due to antibiotic resistance in the previous alternative treatment options. Cases of resistance in this remaining class of antibiotics also are a worsening problem with treatment failures seen abroad though not yet in the US.

Wetzler and his team investigate innate and adaptive immunity – primarily in regards to vaccine development. He has done extensive research and has more than 50 publications regarding mostly Neisseria gonorrhoeae and Neisseria meningitides, the pathogens responsible for gonorrhea and a common cause of meningitis respectively. The team analyzes specific bacterial surface molecules in order to determine which antigens will trigger the appropriate host immune response seen in vaccination.

According to Wetzler, gonorrhea has numerous medical and public health repercussions. “This disease has potentially devastating outcomes specifically in women, causing pelvic inflammatory disease, tubal fibrosis and ectopic pregnancies. Additionally, concurrent gonorrhea infection in HIV patients facilitates the transmission of HIV by increasing viral replication,” he said.

Worldwide 88 million new cases of gonorrhea develop each year. In the setting of limited treatment options, abatement of the disease via vaccine is crucial. Wetzler and his team are optimistic that over the next few years they will make significant headway in regards to prevent this widespread and morbid disease.