Jason Rosch, PhD, Department of Infectious Diseases, discusses St. Jude’s Universal Live Attenuated Streptococcus Pneumonia Bacteria Vaccine and how it protects against pneumonia, acute sinusitis, and otitis media. It consists of a genetically modified bacterium that is unable to cause tissue damage or massive inflammation, does not translocate to the blood stream and is rapidly cleared from the body. Another advantage over currently approved vaccines is its ability to recognize bacteria independent of different serotypes, whereas approved vaccines only cover 13 of the over 100 serotypes. Our vaccine generates antibodies against both the bacteria’s polysaccharide capsule and the bacteria’s serotypes, or protein targets.
Acute otitis media caused by Streptococcus pneumoniae remains one of the most common infectious diseases worldwide despite widespread vaccination. A major limitation of the currently licensed pneumococcal vaccines is the lack of efficacy against mucosal disease manifestations such as acute otitis media, acute bacterial sinusitis, and pneumonia. We sought to generate a novel class of live vaccines that are fully attenuated and retain all major antigenic virulence proteins. A live vaccine candidate based on deletion of the signal recognition pathway component ftsY induced potent, serotype-independent protection against otitis media, sinusitis, pneumonia, and invasive pneumococcal disease. Protection was maintained in animals coinfected with influenza virus, but was lost if mice were depleted of CD4+ T-cells at the time of vaccination. Compared to the commercial conjugate vaccine that promotes IgG1 production in mice, the live vaccine induced a strong serum IgG2a and IgG2b response that correlated with CD4+ T-cell mediated class switching. Deletion of genes required for microbial adaptation to the host environment is a novel strategy for development of live, attenuated vaccines that retain potentially antigenic virulence factors.
otitis media, streptococcus pneumonia, vaccine, bacterial sinusitis, attenuated, live, serotype-independent
Granted Patents or Published Applications
Provisional patent application pending.
Related Scientific References
Rosch, J.W. et al., “A live-attenuated pneumococcal vaccine elicits CD4+ T-cell dependent class switching and provides serotype independent protection against acute otitis media”, EMBO online Nov. 4, 2013, DOI: 10.1002/emmm.201202150263 (2013)
Acute otitis media or middle ear infection remains one of the most common infectious diseases worldwide. It is the most common infection for which antibiotics are prescribed in the US despite widespread vaccination. Pneumonia is the single largest cause of death in children worldwide, affecting over 1.5 Million each year. In the US there are over 6 Million infections annually. Pneumonia is also the largest killer in the elderly.
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