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PloS One 2018Respiratory tract infections and invasive disease caused by Streptococcus pneumoniae in high-risk groups are a major global health problem. Available human vaccines have...
Nasal immunization with recombinant chimeric pneumococcal protein and cell wall from immunobiotic bacteria improve resistance of infant mice to Streptococcus pneumoniae infection.
Respiratory tract infections and invasive disease caused by Streptococcus pneumoniae in high-risk groups are a major global health problem. Available human vaccines have reduced immunogenicity and low immunological memory in these populations, as well as high cost as a public health strategy in poor communities. In addition, no single pneumococcal protein antigen has been able to elicit protection comparable to that achieved using protein-polysaccharide conjugate vaccines. In this context, chimeric pneumococcal proteins raise as potential good vaccine candidates because of their simplicity of production and reduced cost. The aim of this work was to study whether the nasal immunization of infant mice with the recombinant chimeric pneumococcal protein (PSFP) was able to improve resistance to S. pneumoniae, and whether the immunomodulatory strain Lactobacillus rhamnosus CRL1505 or its cell wall (CW1505) could be used as effective mucosal adjuvants. Our results showed that the nasal immunization with PSPF improved pneumococcal-specific IgA and IgG levels in broncho-alveolar lavage (BAL), reduced lung bacterial counts, and avoided dissemination of pneumococci into the blood. Of interest, immunization with PSPF elicited cross-protective immunity against different pneumococcal serotypes. It was also observed that the nasal immunization of infant mice with PSPF+CW1505 significantly increased the production of pneumococcal-specific IgA and IgG in BAL, as well as IgM and IgG in serum when compared with PSPF alone. PSPF+CW1505 immunization also improved the reduction of pneumococcal lung colonization and its dissemination in to the bloodstream when compared to PSPF alone. Our results suggest that immunization with PSPF together with the cell wall of the immunomodulatory strain L. rhamnosus CRL1505 as a mucosal adjuvant could be an interesting alternative to improve protection against pneumococcal infection in children.
Topics: Adjuvants, Immunologic; Administration, Intranasal; Animals; Antibodies, Bacterial; Antigens, Bacterial; Bacterial Proteins; Cell Wall; Child; Cross Protection; Cytokines; Humans; Immunity, Mucosal; Immunization; Lacticaseibacillus rhamnosus; Lung; Male; Mice; Pneumococcal Infections; Pneumococcal Vaccines; Pneumonia, Pneumococcal; Recombinant Fusion Proteins; Streptococcus pneumoniae
PubMed: 30395582
DOI: 10.1371/journal.pone.0206661 -
Infection and Immunity Nov 2014Streptococcus pneumoniae (pneumococcus) is both a widespread nasal colonizer and a leading cause of otitis media, one of the most common diseases of childhood....
Streptococcus pneumoniae (pneumococcus) is both a widespread nasal colonizer and a leading cause of otitis media, one of the most common diseases of childhood. Pneumococcal phase variation influences both colonization and disease and thus has been linked to the bacteria's transition from colonizer to otopathogen. Further contributing to this transition, coinfection with influenza A virus has been strongly associated epidemiologically with the dissemination of pneumococci from the nasopharynx to the middle ear. Using a mouse infection model, we demonstrated that coinfection with influenza virus and pneumococci enhanced both colonization and inflammatory responses within the nasopharynx and middle ear chamber. Coinfection studies were also performed using pneumococcal populations enriched for opaque or transparent phase variants. As shown previously, opaque variants were less able to colonize the nasopharynx. In vitro, this phase also demonstrated diminished biofilm viability and epithelial adherence. However, coinfection with influenza virus ameliorated this colonization defect in vivo. Further, viral coinfection ultimately induced a similar magnitude of middle ear infection by both phase variants. These data indicate that despite inherent differences in colonization, the influenza A virus exacerbation of experimental middle ear infection is independent of the pneumococcal phase. These findings provide new insights into the synergistic link between pneumococcus and influenza virus in the context of otitis media.
Topics: Animals; Carrier State; Coinfection; Influenza A virus; Mice; Nose; Orthomyxoviridae Infections; Otitis Media; Pneumococcal Infections; Streptococcus pneumoniae
PubMed: 25156728
DOI: 10.1128/IAI.01856-14 -
Journal of Microbiology, Immunology,... Jun 2023Serotype 3 has persisted to be an important cause of invasive pneumococcal disease in adults in the post-vaccine era. We aimed to investigate clinical and... (Observational Study)
Observational Study
BACKGROUND/PURPOSE
Serotype 3 has persisted to be an important cause of invasive pneumococcal disease in adults in the post-vaccine era. We aimed to investigate clinical and microbiological characteristics of Streptococcus pneumoniae serotype 3 infection in Taiwan and identify the risk factors associated with severe clinical outcome.
METHODS
A multicenter observational study was conducted to analyze serotype 3 isolates collected between 2012 and 2021. Demographics, comorbidities, and risk categories were statistically compared with clinical outcome. Antimicrobial susceptibility testing and multilocus sequence typing were performed.
RESULTS
A total of 146 isolates were collected, including 12 isolates regarded as colonizers. Among 134 infected cases, 54 (40.3%) were aged 65 and older. Mortality was significantly associated with diabetes mellitus, immunosuppression, immunodeficiency, high-risk status, and older age. Susceptibility rates were high to levofloxacin (98.9%), moxifloxacin (100%), vancomycin (100%), and ceftriaxone (97.3%). 25.3% (37/146) of the isolates showed intermediate susceptibility and 0.7% (1/146) showed resistance to penicillin. ST180 was the dominant sequence type. ST13 and ST9625 isolates were less susceptible to penicillin and ceftriaxone.
CONCLUSIONS
Serotype 3 infection showed a high mortality rate, especially in patients with older ages and comorbidities. Although the incidence rates decreased during the COVID-19 pandemic, serotype 3 remained as an important cause of infection after the implementation of PCV13. Developing a more effective vaccine against serotype 3 and monitoring the antimicrobial-resistant sequence types are necessary.
Topics: Adult; Humans; Streptococcus pneumoniae; Ceftriaxone; Serogroup; Pandemics; COVID-19; Pneumococcal Infections; Multilocus Sequence Typing; Risk Factors; Penicillins; Anti-Infective Agents; Anti-Bacterial Agents; Pneumococcal Vaccines; Serotyping; Microbial Sensitivity Tests
PubMed: 36774315
DOI: 10.1016/j.jmii.2023.01.013 -
Frontiers in Immunology 2018() is a colonizer of the human nasopharynx (NP), causing a variety of infections in humans including otitis media, pneumonia, sepsis, and meningitis. The NP is an... (Review)
Review
() is a colonizer of the human nasopharynx (NP), causing a variety of infections in humans including otitis media, pneumonia, sepsis, and meningitis. The NP is an immune permissive site which allows for the persistence of commensal bacteria. Acute or chronic respiratory airway inflammation constitutes a significant risk factor for the manifestation of infections. The inflammatory conditions caused by an upper respiratory viral infection or respiratory conditions such as allergic asthma and chronic obstructive pulmonary disorders (COPDs) are implicated in the dysregulation of airway inflammation and tissue damage, which compromise the respiratory barrier integrity. These immune events promote bacterial outgrowth leading to dissemination and invasion into the bloodstream. Therefore, suppression of inflammation and restoration of respiratory barrier integrity could contain infections manifesting in the backdrop of an inflammatory disease condition. The gained knowledge could be harnessed in the design of novel therapeutic interventions to circumvent bacterial infections.
Topics: Animals; Humans; Inflammation; Otitis Media; Pneumococcal Infections; Pulmonary Disease, Chronic Obstructive; Risk Factors; Streptococcus pneumoniae
PubMed: 30333833
DOI: 10.3389/fimmu.2018.02275 -
Microbiology Spectrum Dec 2022Metal ions are required by all organisms for the chemical processes that support life. However, in excess they can also exert toxicity within biological systems. During...
Metal ions are required by all organisms for the chemical processes that support life. However, in excess they can also exert toxicity within biological systems. During infection, bacterial pathogens such as Streptococcus pneumoniae are exposed to host-imposed metal intoxication, where the toxic properties of metals, such as copper, are exploited to aid in microbial clearance. However, previous studies investigating the antimicrobial efficacy of copper have reported variable findings. Here, we use a highly copper-sensitive strain of S. pneumoniae, lacking both copper efflux and intracellular copper buffering by glutathione, to investigate how copper stress is managed and where it is encountered during infection. We show that this strain exhibits highly dysregulated copper homeostasis, leading to the attenuation of growth and hyperaccumulation of copper In a murine infection model, whole-tissue copper quantitation and elemental bioimaging of the murine lung revealed that infection with S. pneumoniae resulted in increased copper abundance in specific tissues, with the formation of spatially discrete copper hot spots throughout the lung. While the increased copper was able to reduce the viability of the highly copper-sensitive strain in a pneumonia model, copper levels in professional phagocytes and in a bacteremic model were insufficient to prosecute bacterial clearance. Collectively, this study reveals that host copper is redistributed to sites of infection and can impact bacterial viability in a hypersusceptible strain. However, in wild-type S. pneumoniae, the concerted actions of the copper homeostatic mechanisms are sufficient to facilitate continued viability and virulence of the pathogen. Streptococcus pneumoniae (the pneumococcus) is one of the world's foremost bacterial pathogens. Treatment of both localized and systemic pneumococcal infection is becoming complicated by increasing rates of multidrug resistance globally. Copper is a potent antimicrobial agent used by the mammalian immune system in the defense against bacterial pathogens. However, unlike other bacterial species, this copper stress is unable to prosecute pneumococcal clearance. This study determines how the mammalian host inflicts copper stress on S. pneumoniae and the bacterial copper tolerance mechanisms that contribute to maintenance of viability and virulence and . This work has provided insight into the chemical biology of the host-pneumococcal interaction and identified a potential avenue for novel antimicrobial development.
Topics: Animals; Mice; Anti-Infective Agents; Bacterial Proteins; Copper; Lung; Pneumococcal Infections; Streptococcus pneumoniae
PubMed: 36413018
DOI: 10.1128/spectrum.02495-22 -
The Cochrane Database of Systematic... Jan 2015Approximately 450,000 children worldwide die of pneumococcal infections each year. The development of bacterial resistance to antimicrobials adds to the difficulty of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Approximately 450,000 children worldwide die of pneumococcal infections each year. The development of bacterial resistance to antimicrobials adds to the difficulty of treatment of diseases and emphasizes the need for a preventive approach. Newborn vaccination schedules could substantially reduce the impact of pneumococcal disease in immunized children, but do not have an effect on the morbidity and mortality of infants less than three months of age. Pneumococcal vaccination during pregnancy may be a way of preventing pneumococcal disease during the first months of life before the pneumococcal vaccine administered to the infant starts to produce protection.
OBJECTIVES
To assess the effect of pneumococcal vaccination during pregnancy for preventing infant infection.
SEARCH METHODS
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 July 2014) and reference lists of retrieved studies.
SELECTION CRITERIA
Randomized controlled trials in pregnant women comparing pneumococcal vaccine with placebo or doing nothing, or with another vaccine to prevent infant infections.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. We contacted study authors for additional information.
MAIN RESULTS
Seven trials were included, but only six trials (919 participants) contributed data. There was no evidence that pneumococcal vaccination during pregnancy reduces the risk of neonatal infection (risk ratio (RR) 0.66; 95% confidence interval (CI) 0.30 to 1.46; two trials, 241 pregnancies, low quality evidence). Although the data suggest an effect in reducing pneumococcal colonization in infants by 16 months of age (average RR 0.33; 95% CI 0.11 to 0.98; one trial, 56 pregnancies), there was no evidence of this effect in infants at two to three months of age (average RR 1.13; 95% CI 0.46 to 2.78; two trials, 146 pregnancies, low quality evidence) or by six to seven months of age (average RR 0.67, 95% CI 0.22 to 2.08; two trials, 148 pregnancies, low quality evidence). None of the trials included in this review reported neonatal death as a result of pneumococcal infection.Neonatal antibody levels were reported as geometric mean and 95% CI. There were inconsistent results between studies. Two studies showed significantly higher immunoglobulin G (IgG) levels in cord blood in the pneumococcal vaccine group when compared with the control group for all serotypes. In contrast, another trial showed no difference in neonatal antibody levels between the pneumococcal vaccine group and the control group.Maternal antibody levels were also reported as geometric mean and 95% CI. One study showed significantly higher IgG levels in maternal serum in women immunized with pneumococcal vaccine when compared with control vaccine regardless of any serotypes. Another study showed significantly higher maternal antibody levels only for serotype 14, but no evidence of an effect for other serotypes.The percentage of women with seroprotection was measured in one trial at delivery and at 12 months post-delivery. At delivery, results favored the intervention group for serotype 6 (RR 1.49, 95% CI 1.31 to 1.69), serotype 14 (RR 1.40, 95% CI 1.25 to 1.56) and serotype 19 (RR 2.29, 95% CI 1.89 to 2.76). There were no group differences seen at 12 months post-delivery for serotypes 6 or 14 (RR 1.06, 95% CI 1.00 to 1.12 and RR 1.06, 95% CI 0.98 to 1.15, respectively), but results favored the intervention group for serotype 19 (RR 1.59, 95% CI 1.37 to 1.85).No significant difference for tenderness at the injection site between women who received pneumococcal vaccine and those who received control vaccine (average RR 3.20; 95% CI 0.32 to 31.54; two trials, 130 women).The overall quality of evidence is low for primary outcomes. Most outcomes had wide confidence intervals crossing the line of no effect, and most of the included trials had small numbers of participants and few events which led to downgrading evidence for imprecision of findings.
AUTHORS' CONCLUSIONS
There is insufficient evidence to assess whether pneumococcal vaccination during pregnancy could reduce infant infections.
Topics: Female; Gestational Age; Humans; Infant; Infant, Newborn; Pneumococcal Infections; Pneumococcal Vaccines; Pregnancy; Randomized Controlled Trials as Topic; Vaccination
PubMed: 25613573
DOI: 10.1002/14651858.CD004903.pub4 -
Vaccine Jan 2020Pneumococcal carriage is a prerequisite for pneumococcal disease. Little is known about whether social contact frequency and intensity are associated with pneumococcal...
BACKGROUND
Pneumococcal carriage is a prerequisite for pneumococcal disease. Little is known about whether social contact frequency and intensity are associated with pneumococcal carriage. In Fiji, indigenous iTaukei have higher prevalence of pneumococcal carriage compared with Fijians of Indian Descent (FID). We hypothesised that contact differences may contribute to ethnic differences in pneumococcal carriage prevalence and density.
METHODS
In 2015, young infants (5-8 weeks), toddlers (12-23 months), children (2-6 years), and caregivers from Suva and surrounding areas, participated in a cross-sectional survey (n = 2014), three years post pneumococcal conjugate vaccine introduction. Demographic and contact data, and nasopharyngeal swabs were collected. Pneumococci were detected, and quantified using quantitative real-time PCR, with molecular serotyping by microarray. Associations between ethnicity, contact, and pneumococcal carriage and density were estimated using multivariable generalised estimating equation regression models.
RESULTS
iTaukei participants had larger household sizes, higher pneumococcal carriage rates, more contacts, and more frequent contacts of longer duration, compared with FID. The odds of vaccine-type carriage increased by 28% (95% CI 8-53%) P < 0.01 in association with physical contact with 7-14 year old children. iTaukei ethnicity was associated with vaccine-type carriage (aOR) 1.73; 95% CI 1.06-2.82, P = 0.03) and non-vaccine type carriage (aOR 5.98; 95% CI 4.47-8.00, P < 0.01). Ethnicity and contact were not associated with pneumococcal density.
CONCLUSIONS
iTaukei had greater frequency and intensity of contact compared with FID. Physical contact was associated with pneumococcal carriage. Observed differences in pneumococcal nasopharyngeal carriage prevalence between iTaukei and FID were not explained by differences in social contact patterns by ethnicity.
Topics: Adolescent; Adult; Carrier State; Child; Child, Preschool; Cross-Sectional Studies; Ethnicity; Female; Fiji; Humans; Infant; Male; Middle Aged; Nasopharynx; Pneumococcal Infections; Pneumococcal Vaccines; Prevalence; Serotyping; Streptococcus pneumoniae
PubMed: 31668367
DOI: 10.1016/j.vaccine.2019.10.030 -
Infection and Immunity Jul 2006We examined the role of the neuraminidases NanA and NanB in colonization and infection in the upper and lower respiratory tract by Streptococcus pneumoniae, as well as... (Comparative Study)
Comparative Study
We examined the role of the neuraminidases NanA and NanB in colonization and infection in the upper and lower respiratory tract by Streptococcus pneumoniae, as well as the role of these neuraminidases in the onset and development of septicemia following both intranasal and intravenous infection. We demonstrated for the first time using outbred MF1 mouse models of infection that both NanA and NanB were essential for the successful colonization and infection of the upper and lower respiratory tract, respectively, as well as pneumococcal survival in nonmucosal sites, such as the blood. Our studies have shown that in vivo a neuraminidase A mutant is cleared from the nasopharynx, trachea, and lungs within 12 h postinfection, while a neuraminidase B mutant persists but does not increase in either the nasopharynx, trachea, or lungs. We also demonstrated both neuraminidase mutants were unable to cause sepsis following intranasal infections. When administered intravenously, however, both mutants survived initially but were unable to persist in the blood beyond 48 h postinfection and were progressively cleared. The work presented here demonstrates the importance of pneumococcal neuraminidase A and for the first time neuraminidase B in the development of upper and lower respiratory tract infection and sepsis.
Topics: Animals; Disease Models, Animal; Female; Isoenzymes; Mice; Neuraminidase; Pneumococcal Infections; Pneumonia, Pneumococcal; Respiratory Mucosa; Sepsis; Streptococcus pneumoniae
PubMed: 16790774
DOI: 10.1128/IAI.01237-05 -
Journal of Korean Medical Science Jan 2013Streptococcus pneumoniae can asymptomatically colonize the nasopharynx and cause a diverse range of illnesses. This clinical spectrum from colonization to invasive... (Review)
Review
Streptococcus pneumoniae can asymptomatically colonize the nasopharynx and cause a diverse range of illnesses. This clinical spectrum from colonization to invasive pneumococcal disease (IPD) appears to depend on the pneumococcal capsular serotype rather than the genetic background. According to a literature review, serotypes 1, 4, 5, 7F, 8, 12F, 14, 18C, and 19A are more likely to cause IPD. Although serotypes 1 and 19A are the predominant causes of invasive pneumococcal pneumonia, serotype 14 remains one of the most common etiologic agents of non-bacteremic pneumonia in adults, even after 7-valent pneumococcal conjugate vaccine (PCV7) introduction. Serotypes 1, 3, and 19A pneumococci are likely to cause empyema and hemolytic uremic syndrome. Serotype 1 pneumococcal meningitis is prevalent in the African meningitis belt, with a high fatality rate. In contrast to the capsule type, genotype is more closely associated with antibiotic resistance. CC320/271 strains expressing serotype 19A are multidrug-resistant (MDR) and prevalent worldwide in the era of PCV7. Several clones of MDR serotype 6C pneumococci emerged, and a MDR 6D clone (ST282) has been identified in Korea. Since the pneumococcal epidemiology of capsule types varies geographically and temporally, a nationwide serosurveillance system is vital to establishing appropriate vaccination strategies for each country.
Topics: Drug Resistance, Multiple, Bacterial; Empyema; Hemolytic-Uremic Syndrome; Humans; Meningitis; Peritonitis; Pneumococcal Infections; Pneumonia, Pneumococcal; Serotyping; Streptococcus pneumoniae
PubMed: 23341706
DOI: 10.3346/jkms.2013.28.1.4 -
Frontiers in Immunology 2023Extensive efforts have been made toward improving effective strategies for pneumococcal vaccination, focusing on evaluating the potential of multivalent protein-based...
Development of a bivalent protein-based vaccine candidate against invasive pneumococcal diseases based on novel pneumococcal surface protein A in combination with pneumococcal histidine triad protein D.
Extensive efforts have been made toward improving effective strategies for pneumococcal vaccination, focusing on evaluating the potential of multivalent protein-based vaccines and overcoming the limitations of pneumococcal polysaccharide-based vaccines. In this study, we investigated the protective potential of mice co-immunization with the pneumococcal PhtD and novel rPspA proteins against pneumococcal sepsis infection. The formulations of each antigen alone or in combination were administered intraperitoneally with alum adjuvant into BALB/c mice three times at 14-day intervals. The production of antigen-specific IgG, IgG1 and IgG2a subclasses, and IL-4 and IFN-γ cytokines, were analyzed. Two complement- and opsonophagocytic-mediated killing activities of raised antibodies on day 42 were also assessed. Finally, the protection against an intraperitoneal challenge with 10 CFU/mouse of multi-drug resistance of ATCC49619 was investigated. Our findings showed a significant increase in the anti-PhtD and anti-rPspA sera IgG levels in the immunized group with the PhtD+rPspA formulation compared to each alone. Moreover, the results demonstrated a synergistic effect with a 6.7- and 1.3- fold increase in anti-PhtD and anti-rPspA IgG1, as well as a 5.59- and 1.08- fold increase in anti-PhtD and anti-rPspA IgG2a, respectively. Co-administration of rPspA+PhtD elicited a mixture of Th-2 and Th-1 immune responses, more towards Th-2. In addition, the highest complement-mediated killing activity was observed in the sera of the immunized group with PhtD+rPspA at 1/16 dilution, and the opsonophagocytic activity was increased from 74% to 86.3%. Finally, the survival rates showed that mice receiving the rPspA+PhtD formulation survived significantly longer (100%) than those receiving protein alone or PBS and exhibited the strongest clearance with a 2 log decrease in bacterial load in the blood 24h after challenge compared to the control group. In conclusion, the rPspA+PhtD formulation can be considered a promising bivalent serotype-independent vaccine candidate for protection against invasive pneumococcal infection in the future.
Topics: Animals; Mice; Streptococcus pneumoniae; Pneumococcal Infections; Vaccines
PubMed: 37680628
DOI: 10.3389/fimmu.2023.1187773