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Human Vaccines & Immunotherapeutics 2016Streptococcus pneumoniae remains one of the most frequent bacterial causes of morbidity and mortality worldwide. National immunization programs implementing pneumococcal... (Review)
Review
Streptococcus pneumoniae remains one of the most frequent bacterial causes of morbidity and mortality worldwide. National immunization programs implementing pneumococcal polysaccharide conjugate vaccines (PCVs) have successfully reduced rates of vaccine-type invasive disease and colonization both via direct effects in immunized children and, in some settings, indirect effects in unimmunized individuals. Limitations of the current PCV approach include the emergence of non-vaccine serotypes contributing to carriage and invasive disease in high-PCV coverage settings and the high cost of goods of PCVs which limits their accessibility in developing countries where the burden of disease remains highest. Furthermore, the distribution of serotypes causing disease varies geographically and includes more serotypes than are currently covered in a single PCV formulation. Researchers have long been exploring the potential of genetically conserved non-capsular pneumococcal antigens as vaccine candidates that might overcome such limitations. To better evaluate the rationale of such approaches, an understanding of the mechanisms of immunity to the various phases of pneumococcal infection is of paramount importance. Herein we will review the evolving understanding of both vaccine-induced and naturally acquired immunity to pneumococcal colonization and infection and discuss how this informs current approaches using serotype-independent pneumococcal vaccine candidates. We will then review the alternative vaccine candidates that have been or are currently under evaluation in clinical trials.
Topics: Antigens, Bacterial; Humans; Immunity, Innate; Immunization Programs; Pneumococcal Infections; Pneumococcal Vaccines; Serogroup; Streptococcus pneumoniae; Vaccination; Vaccines, Conjugate
PubMed: 26535755
DOI: 10.1080/21645515.2015.1087625 -
American Journal of Public Health Apr 2018
Topics: Adult; Chicago; Humans; Illinois; Influenza Vaccines; Influenza, Human; Pneumococcal Vaccines; Vaccination
PubMed: 29513592
DOI: 10.2105/AJPH.2018.304326 -
Human Vaccines & Immunotherapeutics 2019Thirteen-valent pneumococcal conjugate vaccine (PCV13) was licensed in adults to address the unmet medical need of vaccine-type community acquired pneumonia (CAP) and...
Thirteen-valent pneumococcal conjugate vaccine (PCV13) was licensed in adults to address the unmet medical need of vaccine-type community acquired pneumonia (CAP) and the limitations of previous plain-polysaccharide vaccines. Since then, some have questioned the utility of adult PCV13 use, arguing that: i) high PCV13 uptake in young children would provide indirect effects that, by themselves, would sufficiently protect unvaccinated adults and ii) no data describing the real-world effectiveness of PCV13 use in adults, especially with immunocompromising conditions, exist. Even in countries like the United States where PCV13 has been routinely recommended for all adults aged ≥ 65 years, the recommendation is contingent on a re-evaluation to determine if continued use is needed in the context of a mature PCV13 pediatric immunization program. Emerging evidence, however, suggests that i) a meaningful burden of PCV13-type pneumococcal pneumonia still persists in adults at increased risk for pneumococcal disease, despite indirect effects from long-standing pediatric PCV13 use, ii) adult PCV13 use is effective and has reduced pneumococcal CAP, even in the elderly and those with chronic medical or immunocompromising conditions - and disease could come back if PCV13 were removed, and iii) ethical and pragmatic vaccine policy considerations support continued adult PCV13 use in countries that have already introduced the vaccine (eg, disparities in adult PCV13 uptake, confusion stemming from removing a previously-recommended vaccine for a non-safety-related concern, and the reality that next-generation PCVs are only a few years away). Together, these findings suggest that continued PCV13 vaccination in adults is needed to control vaccine-type CAP.
Topics: Adult; Child; Community-Acquired Infections; Decision Making; Humans; Immunization Programs; Pneumococcal Vaccines; Pneumonia, Pneumococcal; Public Health; Randomized Controlled Trials as Topic
PubMed: 30352017
DOI: 10.1080/21645515.2018.1538611 -
Human Vaccines & Immunotherapeutics 2014Until 1990, Hemophilus influenzae type b (HITB) was a major cause of morbidity and mortality in toddlers and young children. A vaccine consisting of purified polyribosyl... (Review)
Review
Until 1990, Hemophilus influenzae type b (HITB) was a major cause of morbidity and mortality in toddlers and young children. A vaccine consisting of purified polyribosyl ribitol phosphate (PRP), the capsular polysaccharide (CPS) of HITB, had been shown to be ineffective as an antigen in the population at risk, and this vaccine was withdrawn from the market within a few years of its introduction. By contrast, the discovery that PRP, when covalently bound to an antigenic protein, stimulated antibody production in infants and toddlers, (1) led to the development of a vaccine that has all but eradicated HITB infection and brought about a near-disappearance of this organism in the United States.
Topics: Adult; Developed Countries; Haemophilus Infections; Haemophilus Vaccines; Haemophilus influenzae type b; Humans; Pneumococcal Vaccines; Pneumonia, Pneumococcal; Polysaccharides; Randomized Controlled Trials as Topic; Vaccines, Conjugate
PubMed: 24786644
DOI: 10.4161/hv.29031 -
The Cochrane Database of Systematic... 2001Infection with Streptococcus pneumoniae is an important cause of pneumonia and other serious illnesses, particularly amongst those with certain high-risk medical... (Review)
Review
BACKGROUND
Infection with Streptococcus pneumoniae is an important cause of pneumonia and other serious illnesses, particularly amongst those with certain high-risk medical conditions such as asthma. Although pneumococcal vaccine is routinely advocated for people with asthma, there is uncertainty about the evidence base that underpins this recommendation.
OBJECTIVES
To determine the efficacy of pneumococcal vaccine in reducing mortality or morbidity from pneumococcal disease in asthmatics.
SEARCH STRATEGY
Randomised controlled trials were identified using the Cochrane Airways Group's register derived from MEDLINE, EMBASE, and CINAHL electronic databases and hand searched respiratory journals and meeting abstracts.
SELECTION CRITERIA
Randomised controlled trials, with or without blinding, in which pneumococcal vaccine has been compared with placebo or no treatment in people with clinician diagnosed asthma.
DATA COLLECTION AND ANALYSIS
Two reviewers independently reviewed all abstracts and full papers of all articles of potential relevance were retrieved. Methodological quality was rated using the Cochrane approach and the Jadad rating scale. Data extraction was performed by one reviewer and checked independently by a second. We planned to perform quantitative analyses of outcomes on an intention-to-treat basis, where possible.
MAIN RESULTS
Of the three papers retrieved, only one satisfied the inclusion criteria and the methodological quality of this study was low (unblinded and inadequate allocation concealment). None of the data could be aggregated in a meta-analysis. Comparisons in a sub-set of 30 asthmatic children prone to recurrent episodes of otitis media, showed that pneumococcal vaccination decreased the incidence of acute asthma exacerbations from 10 to 7 (per child per year).
REVIEWER'S CONCLUSIONS
This review found very limited evidence to support the routine use of pneumococcal vaccine in people with asthma. A randomised trial of vaccine efficacy in children and adults with asthma is needed.
Topics: Asthma; Humans; Pneumococcal Vaccines; Pneumonia, Pneumococcal
PubMed: 11687018
DOI: 10.1002/14651858.CD002165 -
Clinical and Vaccine Immunology : CVI May 2016Controversy exists regarding the optimal use of the 23-valent pneumococcal conjugate vaccine for the protection of high-risk individuals, such as children and adults... (Review)
Review
Controversy exists regarding the optimal use of the 23-valent pneumococcal conjugate vaccine for the protection of high-risk individuals, such as children and adults with immunocompromising conditions and the elderly. The effectiveness and immunogenicity of 23-valent pneumococcal polysaccharide vaccine (PPV23) are limited in such high-risk populations compared to the healthy, with meta-analyses failing to provide robust evidence on vaccine efficacy against invasive pneumococcal disease (IPD) or pneumonia. Moreover, several studies have demonstrated a PPV23-induced state of immune tolerance or hyporesponsiveness to subsequent vaccination, where the response to revaccination does not reach the levels achieved with primary vaccination. The clinical significance of hyporesponsiveness is not yet clarified, but attenuated humoral and cellular response could lead to reduced levels of protection and increased susceptibility to pneumococcal disease. As disease epidemiology among high-risk groups shows that we are still in need of maximum serotype coverage, the optimal use of PPV23 in the context of combined conjugate/polysaccharide vaccine schedules is an important priority. In this minireview, we discuss PPV23-induced hyporesponsiveness and its implications in designing highly effective vaccination schedules for the optimal protection for high-risk individuals.
Topics: Adult; Aged; Child; Humans; Immune Tolerance; Immunization Schedule; Immunization, Secondary; Immunocompromised Host; Immunogenicity, Vaccine; Pneumococcal Infections; Pneumococcal Vaccines; Pneumonia, Pneumococcal; Risk Factors; Vaccination
PubMed: 27009210
DOI: 10.1128/CVI.00721-15 -
Frontiers in Immunology 2019Current guidelines encourage administering pneumococcal vaccine Prevnar-13 to patients with lupus, but whether such vaccinations affect disease severity is unclear. To...
Current guidelines encourage administering pneumococcal vaccine Prevnar-13 to patients with lupus, but whether such vaccinations affect disease severity is unclear. To address this issue, we treated 3-month-old MRL- mice, that spontaneously develop a lupus-like syndrome, with Prevnar-13 or vehicle control. After 3 months, we quantified circulating anti-Pneumococcal polysaccharide capsule (PPS) antibodies and signs of disease severity, including albuminuria, renal histology and skin severity score. We also compared immunophenotypes and function of T and B cells from treated and untreated animals. Prevnar-13 elicited the formation of anti-pneumococcal IgM and IgG. Prevnar-13 treated animals showed reduced albuminuria, renal histological lesions, and milder dermatitis compared to vehicle-treated controls. Mitigated disease severity was associated with reduced and increased T follicular helper cells (T) and T follicular regulatory cells (T), respectively, in Prevnar-treated animals. T cells from Prevnar-13 vaccinated mice showed differential cytokine production after aCD3/aCD28 stimulation, with significantly decreased IL-17 and IL-4, and increased IL-10 production compared to non-vaccinated mice. In conclusion, pneumococcal vaccination elicits anti-pneumococcal antibody response and ameliorates disease severity in MRL- mice, which associates with fewer T and increased T. Together, the data support use of Prevnar vaccination in individuals with SLE.
Topics: Animals; Antibodies, Bacterial; Disease Models, Animal; Lupus Erythematosus, Systemic; Mice; Mice, Inbred MRL lpr; Pneumococcal Vaccines; T-Lymphocytes
PubMed: 31824490
DOI: 10.3389/fimmu.2019.02695 -
PloS One 2017Routine vaccination of elderly people against pneumococcal diseases is recommended in many countries. National guidelines differ, recommending either the 23-valent... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Routine vaccination of elderly people against pneumococcal diseases is recommended in many countries. National guidelines differ, recommending either the 23-valent polysaccharide vaccine (PPV23), the 13-valent conjugate vaccine (PCV13) or both. Considering the ongoing debate on the effectiveness of PPV23, we performed a systematic literature review and meta-analysis of the vaccine efficacy/effectiveness (VE) of PPV23 against invasive pneumococcal disease (IPD) and pneumococcal pneumonia in adults aged ≥60 years living in industrialized countries.
METHODS
We searched for pertinent clinical trials and observational studies in databases MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews. We assessed the risk of bias of individual studies using the Cochrane Risk of Bias tool for randomized controlled trials and the Newcastle-Ottawa Scale for observational studies. We rated the overall quality of the evidence by GRADE criteria. We performed meta-analyses of studies grouped by outcome and study design using random-effects models. We applied a sensitivity analysis excluding studies with high risk of bias.
RESULTS
We identified 17 eligible studies. Pooled VE against IPD (by any serotype) was 73% (95%CI: 10-92%) in four clinical trials, 45% (95%CI: 15-65%) in three cohort studies, and 59% (95%CI: 35-74%) in three case-control studies. After excluding studies with high risk of bias, pooled VE against pneumococcal pneumonia (by any serotype) was 64% (95%CI: 35-80%) in two clinical trials and 48% (95%CI: 25-63%) in two cohort studies. Higher VE estimates in trials (follow-up ~2.5 years) than in observational studies (follow-up ~5 years) may indicate waning protection. Unlike previous meta-analyses, we excluded two trials with high risk of bias regarding the outcome pneumococcal pneumonia, because diagnosis was based on serologic methods with insufficient specificity.
CONCLUSIONS
Our meta-analysis revealed significant VE of PPV23 against both IPD and pneumococcal pneumonia by any serotype in the elderly, comparable to the efficacy of PCV13 against vaccine-serotype disease in a recent clinical trial in elderly people. Due to its broader serotype coverage and the decrease of PCV13 serotypes among adults resulting from routine infant immunization with PCV13, PPV23 continues to play an important role for protecting adults against IPD and pneumococcal pneumonia.
Topics: Age Factors; Aged; Aged, 80 and over; Clinical Trials as Topic; Female; Humans; Male; Odds Ratio; Outcome Assessment, Health Care; Pneumococcal Infections; Pneumococcal Vaccines; Streptococcus pneumoniae
PubMed: 28061505
DOI: 10.1371/journal.pone.0169368 -
Human Vaccines & Immunotherapeutics 2018Streptococcus pneumoniae is a major human bacterial pathogen responsible for millions of deaths each year and significantly more illnesses worldwide. With over 90... (Review)
Review
Streptococcus pneumoniae is a major human bacterial pathogen responsible for millions of deaths each year and significantly more illnesses worldwide. With over 90 different serotypes, providing effective vaccine programs has been a continuing challenge. Since 1983, the world has been introduced to four different pneumococcal vaccines (PPSV23, PCV7, PCV10, and PCV13) each with their own complications and successes. Since vaccination programs began, a decrease in the overall rate of pneumococcal pneumonia and associated diseases has been observed, notably in higher risk populations. However, with a decrease in incidence of vaccine type pneumococcal serotypes, increases in non-vaccine serotypes of the bacteria have been observed along with serotype switching. Additionally, a rise in antibiotic resistant strains of S. pneumoniae is noted. Here we discuss both the positive and negative clinical manifestations of pneumonia vaccine programs and discuss the challenges in pneumococcal vaccine design.
Topics: Bacteremia; Drug Development; Drug Resistance, Bacterial; Humans; Incidence; Meningitis, Bacterial; Pneumococcal Infections; Pneumococcal Vaccines; Serogroup; Streptococcus pneumoniae
PubMed: 29757699
DOI: 10.1080/21645515.2018.1470726 -
Clinical Microbiology and Infection :... Feb 2020Streptococcus pneumoniae is the most common pathogen causing bacterial meningitis. The routine use of multivalent conjugate pneumococcal vaccines has led to a decline of... (Review)
Review
BACKGROUND
Streptococcus pneumoniae is the most common pathogen causing bacterial meningitis. The routine use of multivalent conjugate pneumococcal vaccines has led to a decline of invasive pneumococcal disease caused by serotypes included in the vaccine serotypes. Recently, several reports have described a concomitant rise in the incidence of non-vaccine serotypes, suggesting serotype replacement.
OBJECTIVE
We aim to review the effect of pneumococcal vaccination on the incidence of pneumococcal meningitis in Europe and northern America with a particular interest in serotype replacement.
SOURCES
Articles that include data on invasive pneumococcal disease incidence before and after the introduction of vaccination, or on invasive pneumococcal serotype, are discussed, with a focus on pneumococcal meningitis.
CONTENT
The introduction of pneumococcal conjugate vaccines has universally resulted in a decline in vaccine-serotype pneumococcal meningitis incidence throughout Europe and northern America. Serotype replacement by non-vaccine serotypes has however been reported following the introduction of the 7-, 10- and 13-valent pneumococcal conjugate vaccines, which in several regions abolished the overall effect of vaccination on pneumococcal meningitis incidence.
IMPLICATIONS
The promising decline in the incidence of pneumococcal meningitis following the introduction of vaccination seems to have been temporary. Replacement by non-vaccine serotypes illustrates that pneumococcal meningitis continues to pose a major challenge. We need new approaches to prevention, new vaccines and continued efforts to improve treatment for patients with pneumococcal meningitis.
Topics: Europe; Heptavalent Pneumococcal Conjugate Vaccine; Humans; Incidence; Meningitis, Pneumococcal; North America; Pneumococcal Infections; Pneumococcal Vaccines; Serogroup; Streptococcus pneumoniae; Vaccination; Vaccines, Conjugate
PubMed: 31100424
DOI: 10.1016/j.cmi.2019.04.032