The future of pneumococcal disease prevention

Rodgers, Gail L.; Klugman, Keith P.

doi:10.1016/j.vaccine.2011.07.047

Cited by 66 publications

(60 citation statements)

References 85 publications

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“…Currently available pneumococcal vaccines are all based on the serotype-specific capsular polysaccharides. However, 93 distinct capsular serotypes have been identified so far (2). Although these polysaccharide-based vaccines have greatly decreased the burden of pneumococcal disease, the limited serotype coverage can be an issue.…”

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confidence: 99%

Mucosal Immunization with Recombinant Fusion Protein DnaJ-ΔA146Ply Enhances Cross-Protective Immunity against Streptococcus pneumoniae Infection in Mice via Interleukin 17A

et al. 2014

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Pneumolysin (Ply) and its variants are protective against pneumococcal infections in animal models, and as a Toll-like receptor 4 agonist, pneumolysin has been reported to be a mucosal adjuvant. DnaJ has been approved as a useful candidate vaccine protein; we therefore designed novel fusion proteins of DnaJ with a form of Ply that has a deletion of A146 (⌬A146Ply-DnaJ [the C terminus of ⌬A146Ply connected with the N terminus of DnaJ] and DnaJ-⌬A146Ply [the C terminus of DnaJ connected with the N terminus of ⌬A146Ply]) to test whether they are protective against focal and lethal pneumococcal infections and their potential protective mechanisms. The purified proteins were used to intranasally immunize the animals without additional adjuvant. Immunization with DnaJ-⌬A146Ply or DnaJ plus ⌬A146Ply (Ply with a single deletion of A146) could significantly reduce S. pneumoniae colonization in the nasopharynx and lung relative with DnaJ alone. Additionally, we observed the best protection for DnaJ⌬A146Ply-immunized mice after challenge with lethal doses of S. pneumoniae strains, which was comparable to that achieved by PPV23. Mice immunized with DnaJ-⌬A146Ply produced significantly higher levels of anti-DnaJ IgG in serum and secretory IgA (sIgA) in saliva than those immunized with DnaJ alone. The production of IL-17A was also striking in DnaJ-⌬A146Ply-immunized mice. IL-17A knockout (KO) mice did not benefit from DnaJ-⌬A146Ply immunization in colonization experiments, and sIgA production was impaired in IL-17A KO mice. Collectively, our results indicate a mucosal adjuvant potential for ⌬A146Ply and that, without additional adjuvant, DnaJ-⌬A146Ply fusion protein exhibits extensive immune stimulation and is effective against pneumococcal challenges, properties which are partially attributed to the IL-17A-mediated immune responses.

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confidence: 99%

Mucosal Immunization with Recombinant Fusion Protein DnaJ-ΔA146Ply Enhances Cross-Protective Immunity against Streptococcus pneumoniae Infection in Mice via Interleukin 17A

et al. 2014

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“…The morbidity and mortality associated with invasive pneumococcal disease may be prevented by vaccination (1). Accurate pathogen serotyping provides important epidemiologic information to guide vaccine composition.…”

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confidence: 99%

Evaluation of Pneumococcal Serotyping by Multiplex PCR and Quellung Reactions

et al. 2013

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“…Children aged \2 years, adults [65 years of age, and immunocompromised individuals remain at highest risk for IPD, defined as isolation of S. pneumoniae from a normally sterile body fluid [7]. Seven pneumococcal serotypes (1, 5, 6A, 6B, 14, 19F, and 23F) cause most cases of IPD in children worldwide [2,8,9]. The extent of disease due to different serotypes can vary by age, ethnicity, country, time, and clinical presentation [4 •• ].…”

Section: Introductionmentioning

confidence: 99%

Current Trends in Streptococcus pneumoniae Infections and Their Treatment

Shetty

Maldonado

2013

Curr Pediatr Rep

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Invasive pneumococcal disease (IPD) is a major cause of pediatric morbidity and mortality in resource-rich and low and middle-income countries (LMICs). Streptococcus pneumoniae can cause a wide spectrum of invasive and non-invasive disease. In resourcerich countries, implementation of 7-valent pneumococcal conjugate vaccine (PCV7) has been a significant public health achievement. Dramatic decrease in pediatric IPD incidence occurred after PCV7 implementation, but emergence of multi-drug-resistant non-vaccine serotypes (especially 19A) remains a concern. The recently introduced 13-valent PCV (PCV13) has the potential to further reduce the burden of IPD due to serotypes not contained in PCV7. Given the diversity of pneumococcal serotypes and the possibility of serotype replacement disease, innovative approaches to development of pneumococcal vaccines are needed. Continued surveillance of pneumococcal serotypes and antimicrobial resistance is crucial to evaluate the impact of PCV13 vaccine. Improved access to PCVs is crucial to reduce morbidity and mortality related to IPD in LMIC.

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The future of pneumococcal disease prevention

Cited by 66 publications

References 85 publications

Mucosal Immunization with Recombinant Fusion Protein DnaJ-ΔA146Ply Enhances Cross-Protective Immunity against Streptococcus pneumoniae Infection in Mice via Interleukin 17A

Mucosal Immunization with Recombinant Fusion Protein DnaJ-ΔA146Ply Enhances Cross-Protective Immunity against Streptococcus pneumoniae Infection in Mice via Interleukin 17A

Evaluation of Pneumococcal Serotyping by Multiplex PCR and Quellung Reactions

Current Trends in Streptococcus pneumoniae Infections and Their Treatment

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