Researchers have developed an experimental vaccine that appears to protect against an increasingly common and particularly deadly form of pneumococcal pneumonia. Details about the vaccine and the study’s findings have been published in the Journal of Infectious Diseases.
Although a pediatric vaccine has dramatically reduced the incidence of pneumococcal disease in children and adults, both by protecting vaccinated children and by reducing person-to-person transmission of the bacterium to others (a phenomenon known as herd immunity), it does not cover all strains of disease-causing pneumococcus.
According to Liise-anne Pirofski, MD, principle investigator and professor of medicine and microbiology and immunology at Yeshiva University’s Albert Einstein College of Medicine, “This problem, coupled with the fact that herd immunity doesn’t protect immunocompromised patients as effectively as people with normal immunity, led us to look for a better vaccine.”
The researchers focused on developing a vaccine against serotype 3—a pneumococcal strain that was not included in the pediatric vaccine used for the past decade and that has emerged as a cause of serious pneumonia in adults and children. Serotype 3 can trigger inflammation so overwhelming that it can result in very severe disease or death.
The goal of the study was to produce a vaccine consisting of a live, attenuated (weakened) version of serotype 3 S. pneumoniae. To create their vaccine, the researchers focused on the serotype 3 gene that codes for pneumolysin, a toxin produced by all pneumococcal strains. The researchers replaced this gene with a synthetic version that they hoped would reduce the amount of toxin produced.
“The novelty of this approach lies in the fact that the gene’s expression would be reduced, but not eliminated,” says J. Robert Coleman, PhD, a postdoctoral fellow in microbiology and immunology at Einstein, who helped develop the gene-modification technique known as synthetic gene customization while a graduate student at Stony Brook University.
Altering the pneumolysin gene in the serotype 3 bacteria resulted in less pneumolysin toxin produced in vitro. When mice were injected with either attenuated or unattenuated serotype 3 bacteria, mice receiving the attenuated strain developed an inflammatory response much weaker than was observed in mice receiving the unattenuated serotype 3 strain. Most important, of the five mice injected with the attenuated strain, four survived a subsequent challenge from the highly virulent unattenuated serotype 3 strain, which was lethal in five of five unvaccinated, control mice.
This method of reducing gene expression had been used for viral pathogens, but this is the first time that gene customization has successfully controlled virulence in bacteria. According to the researchers, the study’s findings could lead to pneumococcal vaccines based on weakened strains. The researchers are now investigating whether they can reduce the expression of other genes associated with pneumococcal virulence.
Source: Albert Einstein College of Medicine