Streptococcus seems to be the Jekyll and Hyde of the bacterial world.
Group A Strep normally causes strep throat, an illness that is no fun for those who contract it, but relatively benign in the grand scheme of things. However, certain rare strains of Strep A, known as "flesh-eating bacteria," cause necrotizing fascitis, which deprives cells of oxygen and leads to widespread tissue death. Infection with those strains can be fatal, and amputation of affected tissues is often the only way to save patients' lives.
Strep B is a similarly two-faced bacterium, except that there it is not the strain but the victim that determines whether infection is a non-event or a potentially lethal one. Specifically, anywhere between 25 percent and 40 percent of women have Strep B infections of the anogenital mucosa, usually without any clinical symptoms whatsoever. However, when the bacteria are passed from mother to baby during birth, serious infection and even death can result.
That has not always been the case; serious Strep B infections of newborns were first reported in the 1970s.
"It came from out of nowhere," Larry Madoff, neonatologist at Brigham and Women's hospital and Harvard Medical School, told reporters at a press conference to detail publications on the subject. But for whatever reason, it apparently is not going away - instead, it's getting worse. Madoff said that over the last 10 years, there also has been a rise in serious Strep B infections in mothers if the bacterium enters the bloodstream, and in elderly patients with pre-existing medical conditions.
Universal screening and prophylactic antibiotics for infected pregnant women have reduced the number of infant deaths due to Strep B infection to about 100 a year in the U.S. Nevertheless, the administration of antibiotics to 25 percent to 40 percent of women giving birth is anything but trivial, and because half of the infant deaths occur within a week of birth, vaccination is thought to be the most promising strategy to prevent infection.
Vaccination, however, has its own challenges. "The good news is that to get protection for babies, it is sufficient to have mothers with sufficiently high antibody titers," Guido Grandi, vice president of research and development at Chiron Vaccines, said at the press conference. "The bad news is that group B strep is not a single species, but divided into a number of [strains]."
In two papers in the July 1, 2005, issue of Science, separate groups of researchers from Chiron Vaccines, which is part of Emeryville, Calif.-based Chiron Corp., reported on using genomic techniques to tackle Group B Strep vaccines. In the first paper, researchers from Chiron Vaccines, based in Siena, Italy, in collaboration with researchers from Harvard Medical School, the U.S. Institute for Genome Research in Rockville, Md., and the University of Messina Medical School in Italy identified a number of proteins that in combination offer the prospect of a vaccine that can protect against all the major circulating strains of the bacteria.
The researchers first scanned the genome sequences of eight Strep B strains that represent the world's most important disease-causing varieties to search for. They identified a combination of four proteins, each of which conferred protection against some but not all of the major Strep B strains. When mice were vaccinated with a combination of the four proteins, their offspring were protected against Strep B infection with any of the major strains.
The researchers pointed out that their genomic approach allows them to identify antigens with no assigned function, and that in fact, all four proteins they used in their vaccine did not a have an assigned function prior to the study. The scientists found that three of the four proteins are components of pilus-like structures; the existence of such structures is described for the first time in a second paper in the same issue of Science by another group of scientists from Chiron Vaccines.
Pili generally allow bacteria to move and attach to other cells; they are known to be important in infectious processes for other types of bacteria, but had not been identified as structural features of Streptococcus bacteria. In the paper, the authors again used reverse vaccinology techniques to identify such pili; they note that the pili are as long as the bacteria themselves but presumably have been missed because they are not easily seen in samples prepared with standard staining techniques.
The researchers noted that the multi-genome analysis and screening that they used in their study offered a powerful strategy for identifying potential vaccine candidates in general. Because the Strep B genome is highly variable and the classical approach of growing target pathogens and purifying different proteins to produce candidate vaccines is time-consuming and difficult even for a single-component vaccine, "so far, a universal vaccine was not technically feasible," said Rino Rappouli, chief scientific officer and head of research at Chiron Vaccines. With the data published in Science, "we have technically solved the problem of making a [universal] vaccine."