Towards New Broader Spectrum Pneumococcal Vaccines:  The Future of Pneumococcal Disease Prevention

Lee, Lucia H.; Gu, Xin; Nahm, Moon H.

doi:10.3390/vaccines2010112

Cited by 26 publications

(22 citation statements)

References 56 publications

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“…Average coverage of circulating isolates by PCV7 in European countries in the period before 2008 was 71%, and rose to 78% for PCV10 and to 87% for PCV13 [13]. In Europe and North America, the serotypes included in PCV10 and PCV13 are estimated to cover approximately 80-85% and 85-90% of IPD, respectively, in children younger than five years of age [14]. Nevertheless, the majority of isolates of children in Vojvodina were obtained from younger than two years, who are the target group for conjugate vaccines only.…”

Section: Discussionmentioning

confidence: 99%

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Streptococcus pneumoniae serotype distribution in Vojvodina before the introduction of pneumococcal conjugate vaccines into the national immunization program

et al. 2016

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Section: Discussionmentioning

confidence: 99%

“…Analyses encompassed isolates from middle ear aspirate (14), bronchoalveolar lavage fluid (4), tissue bioptate (1), and wound swab (1). Invasive strains (83) were obtained from blood (48), cerebrospinal fluid (17), pleural fluid (17), and pericardial fluid (1) ( Table 1).…”

Section: Methodsmentioning

confidence: 99%

Streptococcus pneumoniae serotype distribution in Vojvodina before the introduction of pneumococcal conjugate vaccines into the national immunization program

et al. 2016

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“…a strong and specific Th2-type response [3]. However, the emergence of new invasive serotypes not covered by existing vaccines demands attention.…”

Section: Introductionmentioning

confidence: 99%

Self-assembled particulate PsaA as vaccine against Streptococcus pneumoniae infection

González-Miró

Rodríguez-Noda

Fariñas-Medina

et al. 2017

Heliyon

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Streptococcus pneumoniae is a human pathogen responsible for the majority of childhood pneumonia and media otitis cases worldwide. The diversity of its capsular polysaccharides (CPS) results in more than 91 serotypes of which at least 23 are virulent. Various CPS conjugated to immunogenic carrier proteins are currently licensed and provide protection against the infection caused by the respective serotypes but not against new and emerging virulent serotypes. In this study, we considered the conserved protein antigen PsaA, the pneumococcal surface adhesin A, in order to overcome the limitations of CPS antigens. The PsaA was translationally fused to a polyhydroxybutyrate (PHB) synthase which mediated production of PsaA displayed on PHB inclusions in recombinant Escherichia coli. This suggested that the PsaA fusion to the PHB synthase did not interfere with PHB synthase activity and its ability to mediate formation of nano-sized inclusions composed of a PHB core surrounded by the PHB synthase fused to PsaA. Isolated PHB beads showed a negative surface charge. Transmission electron microscopy analysis suggested that the PsaA fusion to the PHB synthase reduced the size of PHB beads from about 500 nm to 100 nm. The integrity and antigenicity of the fusion protein attached to isolated PHB beads was confirmed by SDS-PAGE, tryptic peptide fingerprinting analysis using MALDI-TOF-MS/MS and immunoblotting using a monoclonal anti-PsaA antibody. Mice immunized with PsaA displaying PHB beads produced high and specific IgG levels dominated by IgG1 isotype. While IgG1 titer were similar between soluble and insoluble PsaA, the IgG2 titers were strongly increased upon vaccination with insoluble PsaA i.e. PsaA displayed on PHB beads. Particulate PsaA-PHB beads elicited IgG antibodies recognizing PsaA in whole cell lysates of seven different serotypes of S. pneumoniae. This study suggested that PHB beads are suitable carriers for PsaA in order to induce a significant and specific Th-2-type immune response.

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“…Despite this, our in-house serotype 15B-specific monoclonal antibody (Hyp15BG5) was partially reactive with serotype 15C polysaccharide (32), suggesting that serotype 15C capsule is partially O-acetylated and, therefore, that the truncated serotype 15C WciZ retains some activity. As serotypes 15B and 15C have increased in prevalence following the clinical use of pneumococcal conjugate vaccines (33) and since serotype 15B polysaccharide may be included in many future vaccines (34), cross-protection against serotype 15C should be clearly determined. Therefore, we have investigated the basis for the partial functionality of the serotype 15C WciZ and cross-opsonization of 23-valent pneumococcal polysaccharide vaccine (PPV23)-elicited antibodies against serotype 15C.…”

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confidence: 99%

The Pneumococcal Serotype 15C Capsule Is Partially O-Acetylated and Allows for Limited Evasion of 23-Valent Pneumococcal Polysaccharide Vaccine-Elicited Anti-Serotype 15B Antibodies

Spencer

Shenoy

Orihuela

et al. 2017

Clin Vaccine Immunol

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As a species, Streptococcus pneumoniae (the pneumococcus) utilizes a diverse array of capsular polysaccharides to evade the host. In contrast to large variations in sugar composition and linkage formation, O-acetylation is a subtle capsular modification that nonetheless has a large impact on capsular shielding and recognition of the capsule by vaccine-elicited antibodies. Serotype 15B, which is included in the 23-valent pneumococcal polysaccharide vaccine (PPV23), carries the putative O-acetyltransferase gene wciZ. The coding sequence of wciZ contains eight consecutive TA repeats [(TA) 8 ]. Replication slippage is thought to result in the addition or loss of TA repeats, subsequently causing frameshift and truncation of WciZ to yield a nonacetylated serotype, 15C. Using sensitive serological tools, we show that serotype 15C isolates whose wciZ contains seven or nine TA repeats retain partial O-acetylation, while serotype 15C isolates whose wciZ contains six TA repeats have barely detectable O-acetylation. We confirmed by inhibition enzyme-linked immunosorbent assay that (TA) 7 serotype 15C is ϳ0.1% as acetylated as serotype 15B, while serotype 15X is nonacetylated. To eliminate the impact of genetic background, we created isogenic serotype 15B, (TA) 7 serotype 15C, and 15BΔwciZ (15X) strains and found that reduction or absence of WciZ-mediated O-acetylation did not affect capsular shielding from phagocytes, biofilm formation, adhesion to nasopharyngeal cells, desiccation tolerance, or murine colonization. Sera from PPV23-immunized persons opsonized serotype 15B significantly but only slightly better than serotypes 15C and 15X; thus, PPV23 may not result in expansion of serotype 15C.KEYWORDS O-acetyltransferase, O-acetylation, capsule diversity, pneumococcal vaccine, capsular polysaccharide, serotyping, replication slippage S treptococcus pneumoniae (the pneumococcus), a Gram-positive human pathogen, mediates pneumonia and invasive diseases such as septicemia and meningitis and colonizes 6 to 76% of the world's pediatric population (1-3). Pneumococcal diseases are the leading cause of death in children under 5 years old (4), and pneumococcal capsular polysaccharide is the organism's most significant virulence factor as it shields the pneumococcus from various chemical and immune assaults (5). As a result, nonencapsulated pneumococci rarely cause pneumonia or invasive pneumococcal disease (6-8). Pneumococcal capsular types differ in their shielding abilities; therefore, some capsule types are more virulent than others (9, 10). Our previous studies have indicated that small chemical modifications of the capsular repeat unit result in differential shielding of closely related serotypes (11,12).An important capsular modification is O-acetylation: an uncharged, but polar, acetyl

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Towards New Broader Spectrum Pneumococcal Vaccines: The Future of Pneumococcal Disease Prevention

Cited by 26 publications

References 56 publications

Streptococcus pneumoniae serotype distribution in Vojvodina before the introduction of pneumococcal conjugate vaccines into the national immunization program

Streptococcus pneumoniae serotype distribution in Vojvodina before the introduction of pneumococcal conjugate vaccines into the national immunization program

Self-assembled particulate PsaA as vaccine against Streptococcus pneumoniae infection

The Pneumococcal Serotype 15C Capsule Is Partially O-Acetylated and Allows for Limited Evasion of 23-Valent Pneumococcal Polysaccharide Vaccine-Elicited Anti-Serotype 15B Antibodies

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