In the early 1970s, when “early-onset” (age under seven days old) and “late-onset” (between seven and 89 days old) group B streptococcal (GBS) meningitis in young infants was first described, nearly a third of the infants affected died and many more were left deaf, blind and developmentally disabled. Public health skeptics were slow to accept how many infant infections were occurring because GBS was not a reportable disease. Unfortunately, it still is not. Also unrecognized were serious GBS infections in pregnant women (in the amniotic fluid, lining of the uterus, bladder, etc.) making them ill just before, during and after delivery, prolonging their hospitalization and, occasionally, resulting in death.
During my training at Boston City Hospital and Harvard Medical School, I met another young researcher, Dr. Dennis Kasper. We began a 30-year collaboration to develop GBS vaccines. First, we discovered that although 25 to 35 percent of pregnant women silently carried GBS, more than 90 percent lacked the protective immunity in their blood to pass to their newborns. Fairly quickly, we received research funding from the National Institutes of Health to isolate and purify the outer polysaccharide surface (capsule) of the most frequent type of GBS associated with meningitis to test as a vaccine. While the vaccine was safe in adults, this and subsequent different serotypes of capsule vaccines did not reliably induce immunity. Dr. Kasper, working with others, then linked a protein (tetanus toxoid) to different capsules to make GBS conjugate vaccines, like the ones we use in infants to protect them against Hemophilus influenzae type b (Hib) and Streptococcus pneumoniae meningitis. During the next 10 years, we tested GBS conjugate vaccines. These conjugate vaccines were safe, induced protective immunity in 90 to 95 percent of adults, produced immunity in the blood that could promote killing of GBS by human infection-fighting cells in the test tube, and this specific immunity could be transferred to newborns from vaccinated mothers.
Beginning in the late 1970s, Dr. Kasper and I took time away from our clinical and research duties to convince vaccine manufacturers to make GBS vaccines. At first there was little interest because “only” 4 million babies were born each year in the United States, which was too small of a profit potential. Then there was (and still is) the fear that giving a pregnant woman a vaccine, no matter how much she and her infant might benefit, would invoke a lawsuit if anything was wrong with the baby. This fear of litigation so intensified that companies developing candidate GBS vaccines in the 1990s cancelled their programs. Now the pharmaceutical industry’s position is that the only way a GBS vaccine can be developed is to have Congress pass a law to protect the industry from expensive lawsuits. The situation in Europe is similar though there are fewer GBS infections in Western Europe than in the United States. Pharmaceutical companies here and abroad refuse to produce a GBS vaccine and they naming potential litigation as the main obstacle.
Three decades have witnessed some progress nonetheless. GBS infection-associated mortality in newborns has fallen to five percent. Today, among all GBS infections in infants, meningitis accounts for approximately 45 percent rather than the approximately 65 percent of the 1970s. And most early-onset infections can be prevented by culture screening during pregnancy and antibiotic treatment during labor. However, some prevention opportunities are missed and there are still no prevention methods for late-onset disease where 35 percent of infants have meningitis. A GBS vaccine could prevent a continuing cause of death, deafness and developmental disability in infants. We have the knowledge; we even have the vaccine ready to produce. What will it take to make it available to the women who need it? When will the uphill race be won?
