NDLI: Live Attenuated Streptococcus pneumoniae Strains Induce Serotype-Independent Mucosal and Systemic Protection in Mice▿

Content Provider	PubMed Central
Author	Roche, Aoife M. King, Samantha J. Weiser, Jeffrey N.
Copyright Year	2007
Abstract	Streptococcus pneumoniae is an important human pathogen causing both mucosal (otitis media and pneumonia) and systemic (sepsis and meningitis) diseases. Due to increasing rates of antibiotic resistance, there is an urgent need to improve prevention of pneumococcal disease. Two currently licensed vaccines have been successful in reducing pneumococcal disease, but there are limitations with their use and effectiveness. Another approach for prevention is the use of live attenuated vaccines. Here we investigate the safety and protection induced by live attenuated strains of S. pneumoniae containing combinations of deletions in genes encoding three of its major virulence determinants: capsular polysaccharide (cps), pneumolysin (ply), and pneumococcal surface protein A (pspA). Both the cps and ply/pspA mutants of a virulent type 6A isolate were significantly attenuated in a mouse model of sepsis. These attenuated strains retained the ability to colonize the upper respiratory tract. A single intranasal administration of live attenuated vaccine without adjuvant was sufficient to induce both systemic and mucosal protection from challenge with a high dose of the parent strain. Immunization with cps mutants demonstrated cross-protective immunity following challenge with a distantly related isolate. Serum and mucosal antibody titers were significantly increased in mice immunized with the vaccine strains, and this antibody is required for full protection, as μMT mice, which do not make functional, specific antibody, were not protected by immunization with vaccine strains. Thus, colonization by live attenuated S. pneumoniae is a potentially safe and less complex vaccine strategy that may offer broad protection.
Related Links	http://dx.doi.org/10.1128/iai.01972-06
Ending Page	2475
Page Count	7
Starting Page	2469
File Format	PDF
ISSN	00199567
e-ISSN	10985522
Journal	Infection and Immunity
Issue Number	5
Volume Number	75
Language	English
Publisher	American Society for Microbiology
Publisher Date	2007-05-01
Access Restriction	Open
Rights Holder	American Society for Microbiology
Subject Keyword	Immunology Microbiology Parasitology Infectious Diseases Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Infectious Diseases Parasitology Immunology Microbiology

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4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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