Protective Efficacy of Pneumococcal Polysaccharide Vaccines

Smit, Pieter W.

doi:10.1001/jama.1977.03280250039019

Cited by 299 publications

(86 citation statements)

References 11 publications

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“…Polysaccharide vaccines demonstrated high efficacy against PP in several classic RCTs conducted in the 1970s among young South African goldminers, who had a very high risk of pneumococcal pneumonia. In this population, highly significant vaccine efficacies of 76-92 % against VT-PP have been observed for various experimental 6-, 12-, and 13-valent PPSVs [72,73]. Even though these findings cannot be applied quantitatively to people aged ≥60 years, or to the current PPSV23 vaccine, they do impressively demonstrate the proof of principle that pure polysaccharide vaccines can provide protection from PP.…”

Section: Comparative Assessment Of Efficacy Data For Ppsv23 and Pcv13mentioning

confidence: 90%

Background paper to the updated pneumococcal vaccination recommendation for older adults in Germany

Falkenhorst

Remschmidt

Harder

et al. 2016

Bundesgesundheitsbl

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are members of the German Standing Committee on Vaccination (STIKO). Bundesgesundheitsblatt -Gesundheitsforschung -Gesundheitsschutz 12 · 2016 1624Tätigkeitsberichte Summary Background and objective The incidence of pneumococcal diseases among adults increases with age. Therefore, Germany's Standing Committee on Vaccination (Ständige Impfkommission, STIKO) has since 1998 recommended vaccination with the 23-valent pneumococcal polysaccharide vaccine (PPSV23) for all people aged ≥60 years. PPSV23 has been the only pneumococcal vaccine licensed for adults until few years ago. Universal pneumococcal vaccination of infants, using a conjugate vaccine, has been recommended by STIKO since 2006. Since then, pneumococcal serotypes contained in conjugate vaccines have declined among cases of pneumococcal disease not only in children, but -through herd protection -also in older adults. The 13-valent pneumococcal conjugate vaccine (PCV13), currently used for most infants in Germany, has now been approved for use in adults as well. Data on the efficacy of PCV13 against clinical endpoints in older adults was published in 2015. For that reason, STIKO investigated whether one of the two vaccines (or the combination of both) should be preferred in order to reduce the burden of pneumococcal diseases in older adults, and at what age the vaccine should be given. Efficacy against invasive pneumococcal diseasesPooled data from 4 randomised controlled trials (RCTs) of PPSV23 in older adults show an efficacy of 73 % against invasive pneumococcal disease (IPD) caused by any serotype (95 % confidence interval [CI], 10-92 %). The IPD cases in these studies were mostly caused by one of the 23 serotypes contained in the vaccine. The efficacy of PCV13 in older adults was investigated in one RCT. Efficacy against IPD by any serotype was 49 % (95 % CI, 21-67 %, modified-intention-to-treat analysis). Efficacy against IPD by the 13 serotypes contained in the vaccine (VT-IPD) was 76 % (95 % CI, 47-90 %). Efficacy against pneumococcal pneumoniaAfter exclusion of 2 RCTs with a high risk of bias, pooled efficacy of PPSV23 against pneumococcal pneumonia (PP) caused by any serotype in the remaining 2 RCTs was 64 % (95 % CI, 35-80 %). In the included observational studies, pooled efficacy ranged from 37 % to 53 %, with broadly overlapping CIs, depending on study type. The efficacy of PCV13 against PP caused by any serotype was 22 % (95 % CI, 2-39 %), and against VT-PP it was 38 % (95 % CI, 14-55 %). Anticipated epidemiological and health economic effectsThe above-mentioned studies do not provide clear evidence of a difference between the two vaccines regarding efficacy against clinical endpoints (IPD, PP) caused by the serotypes contained in the respective vaccine. In the 2015-'16 season, 70 % of IPD cases in people aged ≥60 years were caused by PPSV23 serotypes, but only 30 % by PCV13 serotypes. Because PPSV23 contains all the serotypes in PCV13 (except for serotype 6A), vaccination with PPSV23 confers broader serotype coverage and can thereby prevent ...

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Section: Comparative Assessment Of Efficacy Data For Ppsv23 and Pcv13mentioning

confidence: 90%

Background paper to the updated pneumococcal vaccination recommendation for older adults in Germany

Falkenhorst

Remschmidt

Harder

et al. 2016

Bundesgesundheitsbl

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“…Using various preparations of isolated pneumococcal polysaccharides, including the commercial pneumococcal PS (PPS) vaccine, Pneumovax-23 (14), we now demonstrate that the polysaccharide Ag itself is ineffective at inducing detectable IgG and, to a lesser extent, IgM responses in vivo in the absence of a distinct second signal, in this case provided by the concomitant and hitherto unappreciated presence of TLR ligands within the PPS preparations. We also show that the presence of a TLR2 ligand(s) in the commercial PPS conjugate vaccine, Prevnar (15), up-regulates the induced IgG anti-PPS response.…”

Section: T He Mechanism By Which Isolated Polysaccharide (Ps;mentioning

confidence: 94%

In Vivo Humoral Immune Responses to Isolated Pneumococcal Polysaccharides Are Dependent on the Presence of Associated TLR Ligands

Sen

Khan

Chen

et al. 2005

The Journal of Immunology

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We determined whether T cell-independent Ig isotype responses to isolated pneumococcal polysaccharides (PPS) required TLR signaling in vivo. IgG anti-PPS responses to PPS3, PPS14, and C-polysaccharide (C-PS) were virtually undetectable in TLR2−/− mice, whereas specific IgM induction was variably reduced compared with wild-type mice. All PPS-containing preparations induced IL-6 and TNF-α from wild-type, but not TLR2−/−, macrophages. TLR2 activity was distinct from that of PPS, in that it was phenol extractable. Immunization of wild-type mice with phenol-extracted PPS14 also resulted in a marked reduction in the IgG, although not the IgM-anti-PPS14, response compared with untreated PPS14. The commercial 23-valent PPS vaccine, Pneumovax-23 also contained TLR ligands (TLR2 and TLR4), which were absolutely critical for the IgG-inducing activity of the vaccine in mice. Finally, the commercial pneumococcal conjugate vaccine, Prevnar, contained a TLR2 ligand(s) that substantially enhanced both the primary and secondary anti-PPS responses in mice, especially the type 1 IgG isotypes. These data strongly suggest the absolute need for a distinct, TLR-dependent second signal for inducing in vivo IgG T cell-independent humoral immune responses to isolated pneumococcal polysaccharide Ags and highlight the potential importance of previously unappreciated copurified and/or contaminating TLR ligands in PPS vaccine preparations.

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“…First, although surface polysaccharides such as capsule have formed the basis for several successful vaccines directed against extracellular pathogens such as Haemophilus influenzae type b, Streptococcus pneumoniae, and certain serotypes of Neisseria meningitidis [46][47][48], this approach is less practical for ExPEC. More than 80 capsular serotypes exist for E. coli strains [49,50].…”

Section: Discussionmentioning

confidence: 99%

A killed, genetically engineered derivative of a wild-type extraintestinal pathogenic E. coli strain is a vaccine candidate

Russo¹,

Beanan²,

Olson³

et al. 2007

Vaccine

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Infections due to extraintestinal pathogenic E. coli (ExPEC) result in significant morbidity, mortality and increased healthcare costs. An efficacious vaccine against ExPEC would be desirable. In this report we explore the use of killed-whole E. coli as a vaccine immunogen. Given the diversity of capsule and O-antigens in ExPEC we have hypothesized that alternative targets are viable vaccine candidates. We have also hypothesized that immunization with a genetically engineered strain that is deficient in the capsule and O-antigen will generate a greater immune response against antigens other than the capsular and O-antigen epitopes than a wild-type strain. Lastly, we hypothesize that mucosal immunization with killed E. coli has the potential to generate a significant immune response. In this study we demonstrated that nasal immunization with a formalin-killed ExPEC derivative deficient in capsule and O-antigen results in a significantly greater overall humoral response compared to its wild-type derivative (which demonstrates that capsule and/or the O-antigen impede the development of an optimal humoral immune response) and a significantly greater immune response against non-capsular and O-antigen epitopes. These antibodies also bound to a subset of heterologous ExPEC strains and enhanced neutrophil-mediated bactericidal activity against the homologous and a heterologous strain. Taken together these studies support the concept that formalin-killed genetically engineered ExPEC derivatives are whole cell vaccine candidates to prevent infections due to ExPEC.

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Protective Efficacy of Pneumococcal Polysaccharide Vaccines

Cited by 299 publications

References 11 publications

Background paper to the updated pneumococcal vaccination recommendation for older adults in Germany

Background paper to the updated pneumococcal vaccination recommendation for older adults in Germany

In Vivo Humoral Immune Responses to Isolated Pneumococcal Polysaccharides Are Dependent on the Presence of Associated TLR Ligands

A killed, genetically engineered derivative of a wild-type extraintestinal pathogenic E. coli strain is a vaccine candidate

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