Science Magazine reports that a group of scientists at Chiron, the Institute for Genomic Research, University of Messina Medical School, and Brigham and Women's, have engineered potential vaccine candidates for Group B Streptococcus using genomic screening techniques or reverse vaccinology.
Group B Strep (GBS) is a leading cause of death in neonates. The bacteria resides in the mucosal tracts of adults, where it can cause infection but is generally not lethal. During birth women can pass the infection to babies, where it can cause sepsis, meningitis and sometimes death. In the U.S. a systematic testing and antibiotic administration program for women in the last weeks of pregnancy is used to prevent infection, however each year the infection causes hundreds of deaths worldwide.
Conventional vaccine development uses various methods, such as the attenuation of the virus advanced by Sabin to produce the polio vaccine, isolation of protein subunits, or recombinant methods to isolate candidate antigens from bacteria or viruses. These resulting proteins are then tested to see which ones if any stimulate immunity (without toxicity) in animals or humans.
Several vaccine strategies specific to GBS exist, such as isolating the polysaccharide capsule (that surrounds the bacteria) which is then conjugated with cholera or pertussis toxin subunits. In addition to the logistical and regulatory challenges of the clinical trials, however, one of the difficulties that these vaccines face is that there are many different serotypes of disease, so a vaccine that is developed for one population say in Europe, may not be suitable for another.
The Chiron group used reverse vaccinology, a technology it had previously investigated for other disease vaccine targets such as type C meningococcal disease, caused by Neisseria meningitidis for which they manufactured a vaccine called Menjugate, used abroad.
Reverse vaccinology uses the whole genome of an organism to isolate all possible antigens "in silico" by comparing the sequence with the sequences of known antigens and toxins, in order to identify likely vaccine antigens. Recombinant expression systems (where the gene is isolated and produced by another bacteria) were used to produce candidate antigens, then these were screened to discern which candidates produced protection against the virulent strains. This method of vaccine development, though not without limitations, has the potential to advance at a faster rate, because the availability of complete genome information accelerates the identification of protein candidates. Chiron explains the difference between conventional vaccine development and this new method here.
The researchers used multiple strains of Group B Streptococcus in their genomic analysis and screening. They ended up with 312 surface proteins that were then screened for protective activity. Four antigens were identified that when tested alone, had restricted activity. These were then combined and the result produced broad spectrum protection against multiple virulent strains of GBS.
