13-valent pneumococcal conjugate vaccine (PCV13)

Jefferies, Johanna M.C.; Macdonald, Emily; Faust, Saul N; Clarke, Stuart C.

doi:10.4161/hv.7.10.16794

Cited by 38 publications

(39 citation statements)

References 46 publications

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“…Here, we investigated DNA damage and repair in the context of human alveolar epithelial cells exposed to three major virulent serotypes of S. pneumoniae (clinical isolate serotype 19F, serotype 3 Xen 10, and serotype 4 TIGR4) that commonly infect young children (42). Among these serotypes, we found that serotype 4 is the most genotoxic and can induce pulmonary DNA damage during acute bacteremic pneumonia.…”

Section: Discussionmentioning

confidence: 99%

Streptococcus pneumoniaesecretes hydrogen peroxide leading to DNA damage and apoptosis in lung cells

Rai

Parrish

Tay

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

131

102

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Streptococcus pneumoniae is a leading cause of pneumonia and one of the most common causes of death globally. The impact of S. pneumoniae on host molecular processes that lead to detrimental pulmonary consequences is not fully understood. Here, we show that S. pneumoniae induces toxic DNA double-strand breaks (DSBs) in human alveolar epithelial cells, as indicated by ataxia telangiectasia mutated kinase (ATM)-dependent phosphorylation of histone H2AX and colocalization with p53-binding protein (53BP1). Furthermore, results show that DNA damage occurs in a bacterial contact-independent fashion and that Streptococcus pyruvate oxidase (SpxB), which enables synthesis of H 2 O 2 , plays a critical role in inducing DSBs. The extent of DNA damage correlates with the extent of apoptosis, and DNA damage precedes apoptosis, which is consistent with the time required for execution of apoptosis. Furthermore, addition of catalase, which neutralizes H 2 O 2 , greatly suppresses S. pneumoniae-induced DNA damage and apoptosis. Importantly, S. pneumoniae induces DSBs in the lungs of animals with acute pneumonia, and H 2 O 2 production by S. pneumoniae in vivo contributes to its genotoxicity and virulence. One of the major DSBs repair pathways is nonhomologous end joining for which Ku70/80 is essential for repair. We find that deficiency of Ku80 causes an increase in the levels of DSBs and apoptosis, underscoring the importance of DNA repair in preventing S. pneumoniaeinduced genotoxicity. Taken together, this study shows that S. pneumoniae-induced damage to the host cell genome exacerbates its toxicity and pathogenesis, making DNA repair a potentially important susceptibility factor in people who suffer from pneumonia.DNA damage | Streptococcus pneumoniae | hydrogen peroxide | γH2AX | Ku80

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Section: Discussionmentioning

confidence: 99%

Streptococcus pneumoniaesecretes hydrogen peroxide leading to DNA damage and apoptosis in lung cells

Rai

Parrish

Tay

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

131

102

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“…PCV13 includes all the seven serotypes included in PCV7, with an additional six serotypes (1, 3, 5, 6A, 7F, and 19A) that cause a majority of IPD [17 •• ]. PCV13 has the potential to address the variation in serotype distribution, and further reduce the burden of IPD [8]. Data from the UK indicate that IPD due to serotypes contained in PCV13 has been reduced by 50 % in children less than 2 years of age [16].…”

Section: Preventionmentioning

confidence: 99%

“…Although the PCV7 vaccination program stated in 2000 has made a substantial impact in preventing pneumococcal disease in the US, non-PCV7 serotype replacement disease has necessitated the development of PCV with expanded serotype coverage [8,17 •• ]. In February 2010, a new PCV13 was recommended in place of PCV7 for routine pediatric immunization in the US from 6 weeks through 71 months of age [17 •• ].…”

Section: Preventionmentioning

confidence: 99%

“…In LMIC, serotypes 1 and 5 are common causes of IPD. Due to efforts from the Global Alliance for Vaccines and Immunization, eight LMIC (Nicaragua, Honduras, Guyana, Sierra Leone, Kenya, and Democratic Republic of Congo, Mali, and Yemen) have introduced PCV13 during 2010-2011 [8]. A 10-valent PCV has also been developed and gained WHO pre-qualification in 2009 [4 •• , 8].…”

Section: Preventionmentioning

confidence: 99%

“…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%

See 2 more Smart Citations

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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Effect of O‐Acetylation on the Antigenicity and Glycoconjugate Immunogenicity of the Streptococcus Pneumoniae Serotype 7F Capsular Polysaccharide

Soubal,

Lugo,

Santana‐Mederos

et al. 2024

ChemBioChem

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Streptococcus pneumoniae is a bacterial pathogen causing diseases as severe as pneumonia, sepsis and meningitis. Commercial pneumococcal conjugate vaccines contain the 7F serotype, which is epidemiologically relevant and highly invasive. This serotype contains an O‐acetyl group at the internal L‐rhamnose of its polysaccharide repeating unit. Herein we report on the role of the O‐acetyl moiety of 7F polysaccharide in both antigen recognition and the induction of a protective antibody response against 7F. Fully and partially de‐O‐acetylated 7F polysaccharides were chemically prepared and compared with the O‐acetylated counterpart in their antigenicity and immunogenicity of their tetanus toxoid glycoconjugates. These comparative studies showed a slight but consistent decrease in the antigenicity for the fully de‐O‐acetylated polysaccharide, but not for the partly de‐O‐acetylated variant. The glycoconjugates derived from the O‐acetylated and the fully de‐O‐acetylated polysaccharides had similar sizes and polysaccharide‐to‐protein ratio, and all proved both to be immunogenic and induce opsonophagocytic responses in mice. Nevertheless, the immune response elicited by the O‐acetylated glycoconjugate was better in both quantity and quality, proving that the O‐acetyl group is not strictly necessary but also not irrelevant for the antigenicity and immunogenicity of the 7F serotype polysaccharide and its glycoconjugates.

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13-valent pneumococcal conjugate vaccine (PCV13)

Cited by 38 publications

References 46 publications

Streptococcus pneumoniaesecretes hydrogen peroxide leading to DNA damage and apoptosis in lung cells

Streptococcus pneumoniaesecretes hydrogen peroxide leading to DNA damage and apoptosis in lung cells

Current Trends in Streptococcus pneumoniae Infections and Their Treatment

Effect of O‐Acetylation on the Antigenicity and Glycoconjugate Immunogenicity of the Streptococcus Pneumoniae Serotype 7F Capsular Polysaccharide

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