A live-attenuated pneumococcal vaccine elicits CD4+ T-cell dependent class switching and provides serotype independent protection against acute otitis media
Article first published online: 4 NOV 2013
© 2013 The Authors.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
EMBO Molecular Medicine
Volume 6, Issue 1, pages 141–154, January 2014
How to Cite
Rosch, J. W., Iverson, A. R., Humann, J., Mann, B., Gao, G., Vogel, P., Mina, M., Murrah, K. A., Perez, A. C., Edward Swords, W., Tuomanen, E. I. and McCullers, J. A. (2014), A live-attenuated pneumococcal vaccine elicits CD4+ T-cell dependent class switching and provides serotype independent protection against acute otitis media. EMBO Mol Med, 6: 141–154. doi: 10.1002/emmm.201202150
- Issue published online: 9 JAN 2014
- Article first published online: 4 NOV 2013
- Manuscript Accepted: 23 SEP 2013
- Manuscript Revised: 6 SEP 2013
- Manuscript Received: 12 OCT 2012
- Public Health Service. Grant Number: ARRA RC1DC010566
- American Lebanese Syrian Associated Charities (ALSAC)
- otitis media;
- S treptococcus ;
Acute otitis media (AOM) 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 AOM, acute bacterial sinusitis and pneumonia. We sought to generate a novel class of live vaccines that (1) retain all major antigenic virulence proteins yet are fully attenuated and (2) protect against otitis media. 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. 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 live attenuated vaccine strategy yielding the first experimental vaccine effective against pneumococcal otitis media.
Pneumococcal vaccines prevent sepsis and meningitis-induced diseases but not otitis media, sinusitis, or pneumonia. A novel live genetically attenuated pneumococcal vaccine is shown protective against mucosal infections in mice and chinchilla models.
- A novel, live attenuated pneumococcal vaccine was generated by targeting genes required for microbial adaptation to the host environment
- The live attenuated vaccine was able to confer effective serotype-independent protection against pneumococcal acute otitis media in the murine model
- The live attenuated vaccine was able to confer effective protection in the chinchilla model of pneumococcal acute otitis media
- The live attenuated vaccine induced potent serotype-independent antibody responses and conferred serotype independent protection against pneumococcal colonization and invasive disease
- The live attenuated vaccine induced antibody subtypes distinct from the current conjugate vaccine and these antibody subtypes were dependent upon CD4+ T-cells during vaccination