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Frontiers in Cellular and Infection... 2022(), or the pneumococcus, is a Gram-positive bacterium that colonizes the upper airway. is an opportunistic pathogen capable of life-threatening disease should it... (Review)
Review
(), or the pneumococcus, is a Gram-positive bacterium that colonizes the upper airway. is an opportunistic pathogen capable of life-threatening disease should it become established in the lungs, gain access to the bloodstream, or disseminate to vital organs including the central nervous system. is encapsulated, allowing it to avoid phagocytosis, and current preventative measures against infection include polyvalent vaccines composed of capsular polysaccharide corresponding to its most prevalent serotypes. The pneumococcus also has a plethora of surface components that allow the bacteria to adhere to host cells, facilitate the evasion of the immune system, and obtain vital nutrients; one family of these are the choline-binding proteins (CBPs). Pneumococcal surface protein A (PspA) is one of the most abundant CBPs and confers protection against the host by inhibiting recognition by C-reactive protein and neutralizing the antimicrobial peptide lactoferricin. Recently our group has identified two new roles for PspA: binding to dying host cells via host-cell bound glyceraldehyde 3-phosphate dehydrogenase and co-opting of host lactate dehydrogenase to enhance lactate availability. These properties have been shown to influence localization and enhance virulence in the lower airway, respectively. Herein, we review the impact of CBPs, and in particular PspA, on pneumococcal pathogenesis. We discuss the potential and limitations of using PspA as a conserved vaccine antigen in a conjugate vaccine formulation. PspA is a vital component of the pneumococcal virulence arsenal - therefore, understanding the molecular aspects of this protein is essential in understanding pneumococcal pathogenesis and utilizing PspA as a target for treating or preventing pneumococcal pneumonia.
Topics: Animals; Antibodies, Bacterial; Bacterial Proteins; Humans; Mice; Mice, Inbred BALB C; Pneumococcal Infections; Pneumococcal Vaccines; Streptococcus pneumoniae
PubMed: 35186799
DOI: 10.3389/fcimb.2022.826264 -
Vaccine May 2023In January 2020 the UK changed from a 2 + 1 schedule for 13-valent pneumococcal conjugate vaccine (PCV13) to a 1 + 1 schedule (doses at 3 and 12 months) based on a... (Randomized Controlled Trial)
Randomized Controlled Trial
In January 2020 the UK changed from a 2 + 1 schedule for 13-valent pneumococcal conjugate vaccine (PCV13) to a 1 + 1 schedule (doses at 3 and 12 months) based on a randomized immunogenicity trial comparing the two schedules. Carriage prevalence measured at the time of booster and 6 months later in 191 of the 213 study infants was 57 % (109/191) and 60 % (114/190) respectively. There were eight episodes of vaccine-type (VT) or vaccine-related 6C carriage in the 2 + 1 and six in the 1 + 1 group; ≥4-fold rises in serotype-specific IgG in 71 children with paired post-booster and follow up blood samples at 21-33 months of age were found in 20 % (7/35) of the 2 + 1 and 15 % (6/41) of the 1 + 1 group. VTs identified in carriage and inferred from serology were similar comprising 3, 19A and 19F. Dropping a priming dose from the 2 + 1 PCV 13 schedule did not increase VT carriage in the study cohort. Ongoing population level carriage studies will be important to confirm this.
Topics: Child; Humans; Infant; Antibodies, Bacterial; Immunization Schedule; Nasopharynx; Pneumococcal Infections; Pneumococcal Vaccines; Streptococcus pneumoniae; United Kingdom; Vaccines, Conjugate
PubMed: 37045683
DOI: 10.1016/j.vaccine.2023.04.017 -
Journal of Immunology (Baltimore, Md. :... Jan 2023persists as a leading cause of bacterial pneumonia despite the widespread use of polysaccharide-based vaccines. The limited serotype coverage of current vaccines has...
persists as a leading cause of bacterial pneumonia despite the widespread use of polysaccharide-based vaccines. The limited serotype coverage of current vaccines has led to increased incidence of nonvaccine serotypes, as well as an increase in antibiotic resistance among these serotypes. Pneumococcal infection often follows a primary viral infection such as influenza virus, which hinders host defense and results in bacterial spread to the lungs. We previously isolated human monoclonal Abs (mAbs) against the conserved surface Ag pneumococcal histidine triad protein D (PhtD), and we demonstrated that mAbs to this Ag are protective against lethal pneumococcal challenge prophylactically and therapeutically. In this study, we elucidated the mechanism of protection of a protective anti-pneumococcal human mAb, PhtD3, which is mediated by the presence of complement and macrophages in a mouse model of pneumococcal infection. Treatment with mAb PhtD3 reduced blood and lung bacterial burden in mice, and mAb PhtD3 is able to bind to bacteria in the presence of the capsular polysaccharide, indicating exposure of surface PhtD on encapsulated bacteria. In a mouse model of secondary pneumococcal infection, protection mediated by mAb PhtD3 and another mAb targeting a different epitope, PhtD7, was reduced; however, robust protection was restored by combining mAb PhtD3 with mAb PhtD7, indicating a synergistic effect. Overall, these studies provide new insights into anti-pneumococcal mAb protection and demonstrate, to our knowledge, for the first time, that mAbs to pneumococcal surface proteins can protect against secondary pneumococcal infection in the mouse model.
Topics: Humans; Animals; Mice; Streptococcus pneumoniae; Antibodies, Monoclonal; Epitopes; Pneumococcal Infections; Lung; Pneumococcal Vaccines; Antibodies, Bacterial; Bacterial Proteins
PubMed: 36351696
DOI: 10.4049/jimmunol.2200349 -
American Journal of Hematology May 2022The optimal schedule of pneumococcal vaccination after allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains controversial. The objective of this study...
The optimal schedule of pneumococcal vaccination after allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains controversial. The objective of this study was to investigate the immunogenicity of a 5-dose pneumococcal vaccination schedule in adult allo-HSCT recipients with and without immunosuppressive therapy. In this prospective cohort study, allo-HSCT recipients received four doses of the 13-valent pneumococcal conjugate vaccine (PCV13) and one dose of the 23-valent pneumococcal polysaccharide vaccine (PPSV23) starting 4-6 months after allo-HSCT. PCV13 was administered at T0, T1, T2, and T8 (T = months from enrollment) and PPSV23 at T10. Serum was collected at T0, T4, T8, T10, and T12, and IgG levels were measured for all 24 vaccine serotypes by immunoassay. The primary outcome was overall seroprotection at T12 defined as an IgG concentration ≥1.3 μg/ml for 17/24 vaccine serotypes in allo-HCST recipients with and without immunosuppressive therapy at baseline. Secondary outcomes were serotype-specific seroprotection and dynamics of IgG levels. We included 89 allo-HSCT recipients in the final analysis. Overall seroprotection was 47% (15/32) for patients without immunosuppressive therapy at baseline versus 24% (11/46) for patients with immunosuppressive therapy (p = .03). Seroprotection was higher for PCV13 serotypes (78% and 54% respectively; p = .03) and lower for PPSV23-unique serotypes (28% and 13% respectively; p = .1). IgG concentrations increased significantly over time for all 24 serotypes. Concluding, although immunogenicity of PCV13 serotypes was reasonable, the poor response to PPSV23 serotypes resulted in an insufficient overall response to pneumococcal vaccination for allo-HSCT recipients. Research into vaccination strategies with higher-valent T-cell-dependent pneumococcal vaccines is needed.
Topics: Adult; Hematopoietic Stem Cell Transplantation; Humans; Pneumococcal Infections; Pneumococcal Vaccines; Prospective Studies; Vaccination; Vaccines, Conjugate
PubMed: 35147238
DOI: 10.1002/ajh.26493 -
Tuberkuloz Ve Toraks Sep 2020Pneumococcal infections are an important cause of mortality and morbidity in Chronic Lung Diseases. However, exacerbations, which make the treatment of diseases very... (Review)
Review
Pneumococcal infections are an important cause of mortality and morbidity in Chronic Lung Diseases. However, exacerbations, which make the treatment of diseases very difficult, and corticosteroids used during treatment carry a great risk of pneumococcal infection and adversely affect the treatment. The most rational way to reduce the negative impact of pneumococcal infections on the clinical and economic burden of Chronic Lung Diseases is vaccination of the risky population. Although, vaccination recommendations are well defined, recommended by national and international guidelines and are paid by health authorities, in Turkey, vaccination rates in adults with chronic lung disease is far below the expected. Since physicians are considered to be the most important and reliable resource that can guide their patients in vaccination, applying pneumococcal vaccination routinely in all patients with chronic lung diagnosis and making it a part of daily practice will greatly contribute to reducing the clinical and economic burden of pneumococcal infections in these patients. In this review, the effects of pneumococcal diseases on chronic lung diseases, the risk and clinical burden of pneumococcal diseases in chronic lung diseases are discussed in the light of guidelines and current literature, and the importance of protection from pneumonia in these patients is emphasized. In addition to general information and efficacy data about pneumococcal vaccines available in our country, application methods and access routes to vaccines are also described.
Topics: Adult; Humans; Immunization Programs; Physicians, Primary Care; Pneumococcal Infections; Pneumococcal Vaccines; Pulmonary Disease, Chronic Obstructive; Risk Factors; Turkey; Vaccination
PubMed: 33295729
DOI: 10.5578/tt.70012 -
Frontiers in Immunology 2019In this review we give an update on the mechanisms of naturally acquired immunity against , one of the major human bacterial pathogens that is a common cause of... (Review)
Review
In this review we give an update on the mechanisms of naturally acquired immunity against , one of the major human bacterial pathogens that is a common cause of pneumonia, septicaemia, and meningitis. A clear understanding of the natural mechanisms of immunity to is necessary to help define why the very young and elderly are at high risk of disease, and for devising new prevention strategies. Recent data has shown that nasopharynx colonization by induces antibody responses to protein and capsular antigens in both mice and humans, and also induces Th17 CD4+ cellular immune responses in mice and increases pre-existing responses in humans. These responses are protective, demonstrating that colonization is an immunizing event. We discuss the data from animal models and humans on the relative importance of naturally acquired antibody and Th17 cells on immunity to at three different anatomical sites of infection, the nasopharynx (the site of natural asymptomatic carriage), the lung (site of pneumonia), and the blood (site of sepsis). Mouse data suggest that CD4+ Th17 cells prevent both primary and secondary nasopharyngeal carriage with no role for antibody induced by previous colonization. In contrast, antibody is necessary for prevention of sepsis but CD4+ cellular responses are not. Protection against pneumonia requires a combination of both antibody and Th17 cells, in both cases targeting protein rather than capsular antigen. Proof of which immune component prevents human infection is less easily available, but two recent papers demonstrate that human IgG targeting protein antigens is highly protective against septicaemia. The role of CD4+ responses to prior nasopharyngeal colonization for protective immunity in humans is unclear. The evidence that there is significant naturally-acquired immunity to independent of anti-capsular polysaccharide has clinical implications for the detection of subjects at risk of infections, and the data showing the importance of protein antigens as targets for antibody and Th17 mediated immunity should aid the development of new vaccine strategies.
Topics: Animals; Antibodies, Bacterial; Humans; Immunity, Cellular; Mice; Nasopharynx; Pneumococcal Infections; Pneumococcal Vaccines; Streptococcus pneumoniae; Th17 Cells; Vaccination
PubMed: 30881363
DOI: 10.3389/fimmu.2019.00358 -
Nature Communications Feb 2023Invasive pneumococcal disease (IPD) risk increases with age for older adults whereas the population size benefiting from pneumococcal vaccines and robustness of...
Invasive pneumococcal disease (IPD) risk increases with age for older adults whereas the population size benefiting from pneumococcal vaccines and robustness of immunogenic response to vaccination decline. We estimate how demographics, vaccine efficacy/effectiveness (VE), and waning VE impact on optimal age for a single-dose pneumococcal vaccination. Age- and vaccine-serotype-specific IPD cases from routine surveillance of adults ≥ 55 years old (y), ≥ 4-years after infant-pneumococcal vaccine introduction and before 2020, and VE data from prior studies were used to estimate IPD incidence and waning VE which were then combined in a cohort model of vaccine impact. In Brazil, Malawi, South Africa and England 51, 51, 54 and 39% of adults older than 55 y were younger than 65 years old, with a smaller share of annual IPD cases reported among < 65 years old in England (4,657; 20%) than Brazil (186; 45%), Malawi (4; 63%), or South Africa (134, 48%). Vaccination at 55 years in Brazil, Malawi, and South Africa, and at 70 years in England had the greatest potential for IPD prevention. Here, we show that in low/middle-income countries, pneumococcal vaccines may prevent a substantial proportion of residual IPD burden if administered earlier in adulthood than is typical in high-income countries.
Topics: Infant; Humans; Aged; Middle Aged; Pneumococcal Infections; Pneumococcal Vaccines; Vaccination; Serogroup; Incidence
PubMed: 36797259
DOI: 10.1038/s41467-023-36624-8 -
Frontiers in Cellular and Infection... 2022is a major cause of invasive diseases such as pneumonia, meningitis, and sepsis, with high associated mortality. Our previous molecular evolutionary analysis revealed...
is a major cause of invasive diseases such as pneumonia, meningitis, and sepsis, with high associated mortality. Our previous molecular evolutionary analysis revealed that the gene , encoding the enzyme β-galactosidase (BgaA), had a high proportion of codons under negative selection among the examined pneumococcal genes and that deletion of significantly reduced host mortality in a mouse intravenous infection assay. BgaA is a multifunctional protein that plays a role in cleaving terminal galactose in -linked glycans, resistance to human neutrophil-mediated opsonophagocytic killing, and bacterial adherence to human epithelial cells. In this study, we performed and assays to evaluate the precise role of as a virulence factor in sepsis. Our assays showed that the deletion of significantly reduced the bacterial association with human lung epithelial and vascular endothelial cells. The deletion of also reduced pneumococcal survival in human blood by promoting neutrophil-mediated killing, but did not affect pneumococcal survival in mouse blood. In a mouse sepsis model, mice infected with an -deleted mutant strain exhibited upregulated host innate immunity pathways, suppressed tissue damage, and blood coagulation compared with mice infected with the wild-type strain. These results suggest that BgaA functions as a multifunctional virulence factor whereby it induces host tissue damage and blood coagulation. Taken together, our results suggest that BgaA could be an attractive target for drug design and vaccine development to control pneumococcal infection.
Topics: Animals; Bacterial Proteins; Blood Coagulation; Disease Models, Animal; Endothelial Cells; Humans; Mice; Pneumococcal Infections; Pneumococcal Vaccines; Pneumonia, Pneumococcal; Sepsis; Streptococcus pneumoniae; Virulence Factors
PubMed: 35846740
DOI: 10.3389/fcimb.2022.844000 -
PloS One 2020This study describes predictors of pneumococcal nasopharyngeal carriage and density in Fiji. We used data from four annual (2012-2015) cross-sectional surveys, pre- and...
This study describes predictors of pneumococcal nasopharyngeal carriage and density in Fiji. We used data from four annual (2012-2015) cross-sectional surveys, pre- and post-introduction of ten-valent pneumococcal conjugate vaccine (PCV10) in October 2012. Infants (5-8 weeks), toddlers (12-23 months), children (2-6 years), and their caregivers participated. Pneumococci were detected and quantified using lytA qPCR, with molecular serotyping by microarray. Logistic and quantile regression were used to determine predictors of pneumococcal carriage and density, respectively. There were 8,109 participants. Pneumococcal carriage was negatively associated with years post-PCV10 introduction (global P<0.001), and positively associated with indigenous iTaukei ethnicity (aOR 2.74 [95% CI 2.17-3.45] P<0.001); young age (infant, toddler, and child compared with caregiver participant groups) (global P<0.001); urban residence (aOR 1.45 [95% CI 1.30-2.57] P<0.001); living with ≥2 children <5 years of age (aOR 1.42 [95% CI 1.27-1.59] P<0.001); low family income (aOR 1.44 [95% CI 1.28-1.62] P<0.001); and upper respiratory tract infection (URTI) symptoms (aOR 1.77 [95% CI 1.57-2.01] P<0.001). Predictors were similar for PCV10 and non-PCV10 carriage, except PCV10 carriage was negatively associated with PCV10 vaccination (0.58 [95% CI 0.41-0.82] P = 0.002) and positively associated with exposure to household cigarette smoke (aOR 1.21 [95% CI 1.02-1.43] P = 0.031), while there was no association between years post-PCV10 introduction and non-PCV10 carriage. Pneumococcal density was positively associated with URTI symptoms (adjusted median difference 0.28 [95% CI 0.16, 0.40] P<0.001) and toddler and child, compared with caregiver, participant groups (global P = 0.008). Predictors were similar for PCV10 and non-PCV10 density, except infant, toddler, and child participant groups were not associated with PCV10 density. PCV10 introduction was associated with reduced the odds of overall and PCV10 pneumococcal carriage in Fiji. However, after adjustment iTaukei ethnicity was positively associated with pneumococcal carriage compared with Fijians of Indian Descent, despite similar PCV10 coverage rates.
Topics: Adolescent; Adult; Age Factors; Carrier State; Child; Child, Preschool; Cross-Sectional Studies; Female; Fiji; Humans; Infant; Logistic Models; Male; Pneumococcal Infections; Pneumococcal Vaccines; Risk Factors; Young Adult
PubMed: 32236150
DOI: 10.1371/journal.pone.0231041 -
Frontiers in Public Health 2023To analyze the impact of pneumococcal conjugate vaccines (PCVs) on the incidence of invasive pneumococcal diseases (IPDs) and pneumococcal antibiotic resistance in...
Impact of the progressive uptake of pneumococcal conjugate vaccines on the epidemiology and antimicrobial resistance of invasive pneumococcal disease in Gipuzkoa, northern Spain, 1998-2022.
OBJECTIVES
To analyze the impact of pneumococcal conjugate vaccines (PCVs) on the incidence of invasive pneumococcal diseases (IPDs) and pneumococcal antibiotic resistance in Gipuzkoa, northern Spain for a 25 years period.
METHODS
All cases of IPD confirmed by culture between 1998 and 2022 in a population of around 427,416 people were included. Pneumococci were serotyped and antimicrobial susceptibility was assessed by the EUCAST guidelines.
RESULTS
Overall, 1,516 isolates were collected. Annual IPD incidence rates (per 100,000 people) declined from 19.9 in 1998-2001 to 11.5 in 2017-19 (42.2% reduction), especially in vaccinated children (from 46.7 to 24.9) and non-vaccinated older adult individuals (from 48.0 to 23.6). After PCV13 introduction, the decrease in the incidence of infections caused by PCV13 serotypes was balanced by the increase in the incidence of non-PCV13 serotypes. In the pandemic year of 2020, IPD incidence was the lowest: 2.81. The annual incidence rates of penicillin-resistant isolates also decreased, from 4.91 in 1998-2001 to 1.49 in 2017-19 and 0.70 in 2020. Since 2017, serotypes 14, 19A, and 11A have been the most common penicillin-resistant types. The incidence of erythromycin-resistant strains declined, from 3.65 to 1.73 and 0.70 in the same years.
CONCLUSION
PCV use was associated with declines in the incidence of IPD and the spread of non-vaccine serotypes, that balanced the beneficial effect off PCV13, some of them showing high rates of antibiotic resistance.
Topics: Child; Humans; Aged; Anti-Bacterial Agents; Vaccines, Conjugate; Spain; Drug Resistance, Bacterial; Pneumococcal Infections; Penicillins
PubMed: 37719737
DOI: 10.3389/fpubh.2023.1238502