Pneumococcal Antibody Responses Research Articles

Serological profiling of pneumococcal proteins reveals unique patterns of acquisition, maintenance and waning of antibodies throughout life.

Streptococcus pneumoniae is a leading cause of morbidity and mortality in children and older adults. Yet knowledge on the development of pneumococcal protein-specific antibody responses throughout life is limited. To investigate this, we measured serum IgG levels to 55 pneumococcal proteins in 11-month old infants (n=73), 24-month old children (n=101), parents (n=99), adults without children <6 years of age (n= 99) and older adults aged >60 years (n=100). Our findings revealed low IgG levels in infancy, with distinct development patterns peaking in adults. A decrease in levels was observed for 27 antigens towards older age. Adults and older adults had increased IgG levels during pneumococcal carriage and at increased exposure risk to S. pneumoniae. Carriage was a stronger predictor than exposure or age for antibody responses. These findings highlight the dynamic nature of naturally acquired humoral immunity to pneumococcal proteins throughout life, offering insights for age-targeted interventions.

51 Polymicrobial necrotizing pneumonia in a 3-year-old child with nearabsent pneumococcal antibody and mitogen interferon-γ responses

51 Polymicrobial necrotizing pneumonia in a 3-year-old child with nearabsent pneumococcal antibody and mitogen interferon-γ responses

Spleen function is reduced in individuals with NR5A1 variants with or without a difference of sex development: a cross-sectional study.

NR5A1 is a key regulator of sex differentiation and has been implicated in spleen development through transcription activation of TLX1. Concerns exist about hypo- or asplenism in individuals who have a difference of sex development (DSD) due to an NR5A1 disease-causing variant. We aimed to assess spleen anatomy and function in a clinical cohort of such individuals and in their asymptomatic family member carriers. Cross-sectional assessment in 22 patients with a DSD or primary ovarian insufficiency and 5 asymptomatic carriers from 18 families, harboring 14 different NR5A1 variants. Spleen anatomy was assessed by ultrasound, spleen function by peripheral blood cell count, white blood cell differentiation, percentage of nonswitched memory B cells, specific pneumococcal antibody response, % pitted red blood cells, and Howell-Jolly bodies. Patients and asymptomatic heterozygous individuals had significantly decreased nonswitched memory B cells compared to healthy controls, but higher than asplenic patients. Thrombocytosis and spleen hypoplasia were present in 50% of heterozygous individuals. Four out of 5 individuals homozygous for the previously described p.(Arg103Gln) variant had asplenia. Individuals harboring a heterozygous NR5A1 variant that may cause DSD have a considerable risk for functional hyposplenism, irrespective of their gonadal phenotype. Splenic function should be assessed in these individuals, and if affected or unknown, prophylaxis is recommended to prevent invasive encapsulated bacterial infections. The splenic phenotype associated with NR5A1 variants is more severe in homozygous individuals and is, at least for the p.(Arg103Gln) variant, associated with asplenism.

Worldwide Index of Serotype-Specific Pneumococcal Antibody Responses (WISSPAR): A curated database of clinical trial data.

The Worldwide Index of Serotype Specific Pneumococcal Antibody Responses (WISSPAR; https://wisspar.com), is a centralized, online platform housing data on immunogenicity from clinical trials of pneumococcal vaccines. The data on WISSPAR are primarily curated from outcomes tables from clinical trials and are made available in a searchable format that can be readily used for downstream analyses. The WISSPAR database includes trials covering numerous vaccine products, manufacturers, dosing schedules, age groups, immunocompromised groups, and geographic regions. Customizable data visualization tools are embedded within the site, or the data can be exported for further analyses. Users can also browse summary information about the clinical trials and their results. WISSPAR provides a platform for analysts and policy makers to efficiently gather, compare, and collate clinical trial data about pneumococcal vaccines.

IRF2BP2 mutation with autoimmune enteropathy, immune deficiency, and respiratory failure

Case historyWe present the case of a 31-year-old Hispanic male with history of recurrent bronchiectasis, invasive aspergillosis, and severe persistent asthma, who is now status post lung transplant for end-stage lung disease. He initially presented at 7 years of age with diarrhea, failure to thrive, and nearly absent immunoglobulin levels (IgG < 33 mg/dL, IgA < 7 mg/dL, IgM = 11 mg/dL, IgE = 4 IU/dL) necessitating IVIG treatment. Small intestinal biopsy showed villous atrophy consistent with autoimmune enteropathy. Sweat chloride was reported as indeterminate (44 me/dL). Initial WBC, platelet, and T- and NK-cell counts were within normal range, and B-cell count and percentage were borderline low. Most recently, he was found to have increased immature B-cell count (CD21low), decreased memory B-cells, and poor pneumococcal vaccine antibody response. Patient has been hospitalized numerous times with increasingly severe bronchiectasis, pneumonitis, and COVID-19 infections twice despite vaccination, leading to respiratory failure and lung transplantation. Family history is negative for immune deficiency and lung diseases. DiscussionOf these 3 VUSs (see the table), the one in IRF2BP2 has the most pathogenic potential due to its autosomal dominant inheritance, its location in a conserved domain (Ring), and previous case reports of pathogenic variants at the same or adjacent alleles 1–3. Baxter et al reported a de novo truncating mutation in IRF2BP2 at codon 536 (c.1606CinsTTT), which is similar to our patient's mutation. This patient was noted to have an IPEX-like presentation, with chronic diarrhea, hypogammaglobulinemia, and recurrent infections. Variant Functional Prediction Score for our variant predicts a potentially high damage effect. There are 2 other case reports of heterozygous mutations in loci adjacent to this allele; one (c.1652G>A)2 with a similar clinical phenotype to our patient and the other (C.625-665 del)3 with primarily inflammatory features and few infections. ImpactThis case highlights a variant in IRF2BP2 associated with severe hypogammaglobulinemia, recurrent pulmonary infections, and autoimmune enteropathy.Table 1(abstract: 126)ClassificationGeneExon/IntronDNA changeProtein changeZygosityInheritanceOMIMAssociated diseaseUncertain significanceIRF2BP22c.1606C>Tp.Gln536TerHeterozygousAutosomal Dominant615332Immunodeficiency Common variable, 14Uncertain SignificanceLRBA30c.4832C>Tp.Thr1611lleHeterozygousAutosomal Recessive606453Immunodeficiency Common variable, 8, with autoimmunityPathogenicCFTR4c.350G>Ap.Arg117HisHeterozygousAutosomal Recessive602421CFTR- related disorders

Reactogenicity and immunogenicity of the second COVID-19 vaccination in patients with inborn errors of immunity or mannan-binding lectin deficiency.

BackgroundPatients with inborn errors of immunity (IEI) are at increased risk for severe courses of SARS-CoV-2 infection. COVID-19 vaccination provides effective protection in healthy individuals. However, it remains unclear whether vaccination is efficient and safe in patients with constitutional dysfunctions of the immune system. Thus, we analyzed the humoral response, adverse reactions and assessed the disease activity of the underlying disease after COVID-19 vaccination in a cohort of patients suffering from IEIs or mannan-binding lectin deficiency (MBLdef).MethodsVaccination response was assessed after basic immunization using the Elecsys anti-SARS-CoV-2 S immunoassay and via Vero E6 cell based assay to detect neutralization capabilities. Phenotyping of lymphocytes was performed by flow cytometry. Patient charts were reviewed for disease activity, autoimmune phenomena as well as immunization status and reactogenicity of the vaccination. Activity of the underlying disease was assessed using a patient global numeric rating scale (NRS).ResultsOur cohort included 11 individuals with common variable immunodeficiency (CVID), one patient with warts hypogammaglobulinemia immunodeficiency myelokathexis (WHIM) syndrome, two patients with X-linked agammaglobulinemia (XLA), one patient with Muckle Wells syndrome, two patients with cryopyrin-associated periodic syndrome, one patient with Interferon-gamma (IFN-gamma) receptor defect, one patient with selective deficiency in pneumococcal antibody response combined with a low MBL level and seven patients with severe MBL deficiency. COVID-19 vaccination was generally well tolerated with little to no triggering of autoimmune phenomena. 20 out of 26 patients developed an adequate humoral vaccine response. 9 out of 11 patients developed a T cell response comparable to healthy control subjects. Tested immunoglobulin replacement therapy (IgRT) preparations contained Anti-SARS-CoV-2 S antibodies implicating additional protection through IgRT.SummaryIn summary the data support the efficacy and safety of a COVID-19 vaccination in patients with IEIs/MBLdef. We recommend evaluation of the humoral immune response and testing for virus neutralization after vaccination in this cohort.

Application of vaccine response in the evaluation of patients with suspected B-cell immunodeficiency: Assessment of responses and challenges with interpretation

Diagnostic vaccination is an integral component in the evaluation of patients suspected to have a B cell or humoral deficiency. Evaluation of antibody production in response to both protein- and polysaccharide-based vaccines aids in distinguishing between specific categories of humoral deficiency. Although assessment of pneumococcal polysaccharide responses is widely available and included in diagnostic guidelines, significant variability still exists in the measurement and interpretation of these responses. Interpretation can also be complicated by age, vaccination history and treatment with immunoglobulin replacement therapy. Despite the challenges and limitations of evaluating pneumococcal polysaccharide vaccine responses, it can provide valuable diagnostic and prognostic information to guide therapeutic intervention. Future efforts are needed to further standardize measurement and interpretation of pneumococcal antibody responses to vaccination and to identify and establish other methods and/or vaccines as alternatives to pneumococcal vaccination to address the challenges in certain patient populations.

Pneumococcal IgG Antibody Responses to 23vPPV in Healthy Controls Using an Automated ELISA.

Measurement of pre- and post-pneumococcal antibody levels after immunization with the 23-valent capsular polysaccharide pneumococcal vaccine (23vPPV) is indicative of a T-independent antibody response. The World Health Organisation ELISA is considered gold standard yet is labor-intensive and technically difficult to perform. Interpretation criteria defining an adequate response to 23vPPV remain controversial. The diagnostic Immunology Laboratory at The Royal Children's Hospital, Melbourne (RCH), performs an in-house multi-serotype automated ELISA. The primary objective of this study was to verify RCH interpretation criteria for the laboratory's automated ELISA. Forty pneumococcal conjugate vaccine (PCV)-naïve healthy adults aged 18 to 25years and 22 PCV-primed healthy children aged 2 to 5years were immunized with 23vPPV. A serum sample was collected immediately prior and 28 to 42 (± 7) days post immunization. Samples were analyzed on the Tecan Freedom Evo 200 ELISA with adequate response defined as post-immunization antibody level of 1.3µg/mL or fourfold rise from baseline in ≥ 10/15 serotypes in adult participants and ≥ 4/8 serotypes in pediatric participants. Thirty-nine (97.5%) adults and 22 (100%) children achieved an adequate response to 23vPPV. In PCV-naïve adults, serotypes contained within the conjugate vaccines were less immunogenic, with 12 (30%) adults not achieving an adequate antibody response when only PCV serotypes were used for interpretation. Our diagnostic laboratory has verified the interpretation criteria used for an automated multi-serotype pneumococcal ELISA method. Clinical Trial Registration: ANZCTR registration number ACTRN12618000822280.

Antibody response in patients with autoimmune inflammatory rheumatic disease after pneumococcal polysaccharide prime vaccination or revaccination

Objective The aim of the study was to assess the pneumococcal antibody response in autoimmune inflammatory rheumatic disease (AIIRD) patients receiving 23-valent pneumococcal polysaccharide vaccine (PPV23) as a prime vaccination or revaccination. Method Antibodies to 12 serotypes occurring in the commonly applied pneumococcal vaccines in Denmark were measured in AIIRD patients receiving biological disease-modifying anti-rheumatic drug (bDMARD) treatment for rheumatoid arthritis, spondyloarthritis, or psoriatic arthritis. Patients with a non-protective level of pneumococcal antibodies (geometric mean pneumococcal antibody level < 1 μg/mL) were invited to receive vaccination with PPV23 followed by control of antibody titre 3 months later. Results In total, 224 (74%) of 301 patients were included in the analyses, of whom 126 patients had previously received PPV23 vaccination. Post-vaccination antibody measurement revealed that only 80 patients (36%) achieved a protective level of antibodies. In a multivariable logistic regression analysis, significantly more patients without a previous PPV23 vaccination history achieved a protective antibody level compared with patients with a history of PPV23 vaccination less than 5 years ago (p = 0.005). This difference was not seen when comparing the former group with patients vaccinated 5 years ago or more. Methotrexate (MTX) treatment at the time of vaccination was associated with a non-protective antibody level (p < 0.001). Conclusion Only 36% of patients with a non-protective antibody level achieved a protective level in response to pneumococcal vaccination. Pneumococcal vaccination within the last 5 years and MTX treatment at the time of vaccination were independently associated with a poor antibody response.

Streptococcus pneumoniae controlled human infection models: Opportunities and challenges

Streptococcus pneumoniae controlled human infection models: Opportunities and challenges

Screening Identifies Suboptimal Vaccination Protection in Illness-Susceptible Elite Athletes.

Some groups of elite athletes have an apparent increased susceptibility to respiratory tract infection (RTI) with implications for their health and athletic performance. In this study, we aim to systemically evaluate vaccine response patterns as a potentially efficacious intervention strategy in elite athletes preparing for Olympic competition. Cross-sectional observational study. A UK Sport-funded Olympic training program. One hundred twenty elite athletes and 10 matched healthy controls were studied. A subset of athletes were classified as RTI highly susceptible (n = 22), RTI nonsusceptible (n = 23), and asthmatic (n = 33), with matched controls also recruited (n = 10, 27 ± 3 years). Serum samples were analysed from participants analysing enzyme-linked immunosorbent assay for Immunoglobulin G (IgG) responses against measles, mumps, rubella, and pneumococcus vaccines. Although a majority of athletes (>90%) had detectable IgG levels against measles and rubella, only 76% had detectable mumps responses, with similar findings apparent in controls. Of those RTI-susceptible and asthmatic athletes, 22% had suboptimal antipneumococcal responses below 30 mg/L. A significant proportion of elite athletes preparing for Olympic competition seem to be at risk of mumps infection. In addition, RTI-susceptible and asthmatic athletes exhibit suboptimal pneumococcal antibody responses, highlighting a need for prospective immune screening in athletes to ensure vaccination strategies are effectively delivered.

Pneumococcal serotype-specific cut-offs based on antibody responses to pneumococcal polysaccharide vaccination in healthy adults

Antibody responses to pneumococcal polysaccharide vaccination are frequently used as a diagnostic tool for humoral immunodeficiencies, part of the larger collection of inborn errors of immunity. Currently, arbitrary criteria, such as a serotype specific titer of >/= 1.3 µg/mL is most often used as a cut-off for interpretation of pneumococcal antibody responses. The magnitude of the antibody response to each of the 23 serotypes in Pneumovax®, and serotype-specific cut-offs in healthy pneumococcal vaccine-naïve adults has not been previously characterized. IgG antibody concentrations were measured prospectively for 23 pneumococcal serotypes pre and 4–6 weeks post-Pneumovax® vaccination in 100 healthy adults, using a multiplex bead-based assay. Antibodies to 19 of 23 serotypes were informative for distinguishing subjects who responded to vaccination, and the serotype threshold was determined to be 9 of 19 serotypes, which characterized an antibody response to pneumococcal vaccination. While this study may facilitate classification of IgG serotype-specific antibody responses post-pneumococcal vaccination in adult patients undergoing diagnostic immunological evaluation for antibody immunodeficiencies or other relevant contexts, additional studies in healthy children and S. pneumoniae protein-conjugate-vaccinated healthy adults will need to be undertaken in the future.

Comparison of Pneumococcal Avidity and Antibody Concentration in Children with Recurrent Infections: A Retrospective Pilot Study

Measurement of pneumococcal antibody concentration is a frequently used parameter for functional antibody response to vaccination. Antibody concentration in response to vaccination and strength of antigen-antibody (avidity) interaction are both important measurements of functional antibody response. Both antibody concentration and avidity contribute to immunity against invasive pneumococcal disease. Higher avidity is correlated with increasing bactericidal activity and opsonophagocytosis. On the other hand, patients with lower pneumococcal avidity may be more likely to develop clinically significant pneumococcal sinopulmonary infections. Nine patients with recurrent bacterial respiratory infections were identified by retrospective chart review as having adequate pneumococcal antibody concentrations, but with low avidity for multiple serotypes following immunization with pneumococcal vaccine polyvalent (PPSV23). We assessed response with IgG replacement therapy in these patients. The mean number of serotypes with a normal antibody response (&gt;1.3 mg/ml) among 9 children following immunization with pneumococcal vaccine polyvalent was 19.1 (range 12-22) of 23 serotypes while the mean number of serotypes with a normal avidity response (≥1.0) was 4.7 (range 2-7) of 23 serotypes. Flow cytometry was performed for 8 of the 9 patients prior to starting SCIG replacement therapy. 100% of the cohort experienced a significant decrease in yearly infection rate after starting immunoglobulin replacement. This is the first study to assess the clinical response to immune globulin replacement in patients with normal pneumococcal antibody response but poor pneumococcal avidity, and suggests that patients with poor pneumococcal avidity but apparent normal response by pneumococcal antibody following PPSV23 may benefit from IgG replacement therapy.

Isolating polysaccharide IgG pneumococcal antibody responses by pre-adsorption of conjugate vaccine serotypes: A modified approach for the conjugate vaccine era

BackgroundAssessment of pure polysaccharide response to the 23-valent pneumococcal polysaccharide vaccine (PPV23) can be biased by previous exposure to the conjugate vaccine (PCV). We applied pre-analytical modification to the existing ELISA by pre-incubating serum with PCV. MethodsPCV-adsorbed and non-adsorbed sera were prepared before measuring the concentration of anti-pneumococcal capsular polysaccharide (PCP) IgG antibodies by the whole pneumococcal ELISA. Paired pre and post-pneumococcal vaccination sera from 73 subjects were analyzed and the baseline anti-PCP IgG for each sample was subtracted from the post-vaccination value to measure vaccine responses. Absolute change in titers and fold changes were then compared between both methods. ResultsIn the PCV-vaccinated group (n = 28), pre-adsorption with PCV significantly reduced the vaccine responses compared to non-adsorbed sera [median increase in anti-PCP titers: 27.55 mg/l and 45.98 mg/l, respectively]. In addition, the median fold change dropped significantly from 3.026 to 2.313. In PPV23-vaccinated immunocompetent subjects (n = 28) there was a significant difference in anti-PCP responses with PCV adsorption [median values: 73.71 mg/l without and 51.04 mg/l with adsorption]. All the antibody deficiency patients (n = 17) displayed poor PPV23 responses. Although PPV23 responsiveness was not statistically different between both methods, we have observed a trend for lower anti-PCP IgG titers in PCV-adsorbed sera compared to non-adsorbed ones. Serotype-specific IgG analysis using a multiplexed bead-based immunoassay performed on 10 paired samples confirmed that the adsorption observed is specific to PCV serotypes. ConclusionPre-analytical modification to the conventional ELISA by removing the PCV-specific serotypes may differentiate true polysaccharide response from recall response induced by previous PCV vaccination.

Comparison of Two Different Criteria for Specific Antibody Deficiency in Patients With Chronic and Recurrent Rhinosinusitis.

BackgroundSpecific antibody deficiency (SAD) is highly associated with chronic rhinosinusitis (CRS) and is defined by inadequate post-vaccination percentage of protective (≥1.3 ug/mL) pneumococcal antibody serotypes divided by total tested serotypes (post-pPA).ObjectiveAlthough < 70% post-pPA has been used commonly as the criterion for SAD, we sought to evaluate the clinical outcome of a different definition of SAD.Methods203 patients aged 6 to 70 years with CRS were classified, retrospectively by pre-vaccination pPA (pre-pPA) and post-pPA by two different criteria. Using 70% as the threshold for adequate pneumococcal antibody (PA) response, patients were classified as: Group A (adequate pre-pPA), Group B (inadequate pre-pPA, adequate post-pPA), Group C (inadequate pre-pPA, inadequate post-pPA, SAD). Using 50% as the threshold, patients were similarly classified as: Group A’, B’ and C’.ResultsThe recurrence rate of sinusitis during the next one year in Group A (pre-pPA ≥70%) was significantly less than that of Group A’ (pre-pPA ≥50%) (10% vs. 34%, P = .03). Group A had lower incidence of sinusitis than Group B (pre-pPA < 70%, post-pPA ≥70%) (10% vs. 34%, P = .025). Among Group B’ patients, the recurrence rate of sinusitis was significantly less among those with post-pPA of ≥70% than those with 50%–69% (28% vs. 69%, P < .01).ConclusionEmployment of a 70% pPA threshold for SAD in comparison to a 50% threshold would decrease the incidence of sinusitis in the next one year by vaccinating patients in 51–69% pPA range. Pre-existing PAs (Group A) yielded a higher protection against sinusitis than vaccine-acquired antibodies (Group B).

Reconstitution of IgG Subclasses following Immunoglobulin Therapy in Adult Primary Hypogammaglobulinemia

Background: Immunoglobulin (Ig) therapy is highly effective in reducing the frequency and severity of infections. However, a subset of patients does not respond adequately. Objective: To determine in adult patients with primary hypogammaglobulinemia (a) if failure to reconstitute IgG subclass(es) is associated with inadequate clinical response, (b) whether reconstitution of IgG subclasses differs between routes of Ig administration, (c) which subclasses contribute to low total IgG, and (d) what are the most commonly impaired Streptococcus pneumoniae serotypes. Methods: A retrospective review of the records of patients with primary hypogammaglobulinemia followed up at the Immunology Clinic between 2010 and 2018 was conducted. Demographic, clinical, and laboratory data were collected. Results: Seventy-one patients with primary hypogammaglobulinemia were included. All subclasses were reconstituted in 85% of the patients. IgG3 and IgG4 were most commonly not reconstituted. Reconstitution occurred in 85% of the patients on intravenous Ig (IVIG), 81% of the patients on conventional subcutaneous Ig (SCIG), and 100% of the patients on enzyme-facilitated subcutaneous Ig (fSCIG). The annual infection rate was 0.87 with IVIG, 0.88 with conventional SCIG, and 0.6 with fSCIG. IgG subclasses contributing to low total IgG included IgG1 (61%), IgG2 (49%), IgG3 (23%), and IgG4 (28%). In patients with concomitant specific antibody deficiency (n = 47), the most commonly impaired antibody responses were against pneumococcal serotypes 3, 4, 6b, 12f, and 23f. Conclusions: Failure to reconstitute subclasses does not correlate with an inadequate clinical response to immunoglobulin therapy in primary hypogammaglobulinemia. Full reconstitution of IgG subclasses was observed with fSCIG. A smaller panel of pneumococcal antibody responses may be used to define specific antibody deficiency.

Persistence of pneumococcal antibodies after primary immunisation with a polysaccharide–protein conjugate vaccine

IntroductionDespite immunisation, antibiotics and intensive care management, infection with Streptococcus pneumoniae remains a major cause of morbidity and mortality in children. The WHO currently recommends vaccinating infants with either a...

Relationship between asthma status and antibody response pattern to 23-valent pneumococcal vaccination

Objective: Asthma poses an increased risk for serious pneumococcal disease, but little is known about the influence of asthma status on the 23-valent serotype-specific pneumococcal antibody response. We examined differences in antibody titers between pre- and post-vaccination with 23-valent pneumococcal polysaccharide vaccine (PPSV-23) in relation to asthma status. Methods: Asthma status was retrospectively ascertained by the Predetermined Asthma Criteria in an existing vaccine cohort through comprehensive medical record review. Twenty-three serotype-specific pneumococcal antibody titers measured at baseline and 4–6 weeks post-vaccination were analyzed. Vaccine responses to PPSV-23 were calculated from pre- to post-vaccine titers for each of the serotypes. Results: Of the 64 eligible and enrolled subjects, 18 (28%) had asthma. Controls (i.e., subjects without asthma) demonstrated a statistically significant fold change response compared to their baseline for all serotypes, while those with asthma did not mount a significant response to serotypes 7F, 22F, and 23F. The overall vaccine response as measured by fold change over baseline was lower in subjects with asthma than controls. Conclusions: Poorer humoral immune responses to PPSV-23 as measured by fold change were more likely to be observed in subjects with asthma compared to controls. We recommend the consideration of asthma status when interpreting vaccine response for immune competence workup through larger studies. Further studies are warranted to replicate these findings.

Molecular characterization of Streptococcus pneumoniae in children living in southwest China and assessment of a potential protein vaccine, rPfbA

BackgroundFew children living in southwest China are vaccinated against Streptococcus pneumoniae (S. pneumoniae), which is an important pathogen in causing high morbidity and high mortality. This study aimed the molecular characterization of S. pneumoniae strains isolated from children and a new vaccine strategy based on a potential protein antigen. MethodsMolecular characterizations, including serotype, virulence gene and pilus analyses, were performed using PCR. Seven housekeeping genes were sequenced to identify the sequence types (STs), and antibiotic resistance was analysed using the microdilution broth method. In addition, we evaluated the protective effects of recombinant plasmin- and fibronectin-binding protein A (rPfbA) in murine pneumococcal infection models by challenge and passive transfer analyses, and assessed cytokine changes after immunization. ResultsThe prevalent serotypes were 19F (31.4%), 19A (21.6%), 6B (13.7%), 14 (11.8%) and 23F (9.8%), and the coverage rates of the 13-valent pneumococcal conjugate vaccine (PCV13) were high in 93.3% of the isolates. The predominant STs were ST271 (23.5%), ST320 (21.6%) and ST876 (11.8%). Most of the S. pneumoniae isolates were resistant to erythromycin (95.1%) and clindamycin (90.2%). The molecular distributions and antibiotic resistance rates of the S. pneumoniae isolates differed between the plateau and the basin regions. More than 93% of the S. pneumoniae isolates carried ply, cbpA, phtD and nanA, and over half of the isolates carried pilus-1, pilus-2 and pfbA. Mucosal immunization with rPfbA induced pneumococcal specific antibody responses which provided to eliminate colonization in lung and nasopharynx, and protection against pneumococcal challenge. ConclusionVaccine strategies based on epidemiological surveillance can be more adaptive to specific areas, reduce costs and protect against changing antigenic sites. We advise that children currently living in southwest China be vaccinated with PCV13.

Serologic response to pneumococcal vaccination in children experiencing recurrent invasive pneumococcal disease

BackgroundSome children are prone to recurrent invasive pneumococcal disease (rIPD) and of these, some respond insufficiently to standard pneumococcal vaccination. Little is known about how to handle these children and if they benefit from additional vaccination. Here, we present results from a nationwide study of pediatric rIPD including data on serotype-specific vaccination response to pneumococcal polysaccharide vaccination (PPV23) and pneumococcal conjugate vaccination (PCV7/13).MethodsA retrospective, population-based study was conducted using The National Streptococcus pneumoniae Registry, which contains laboratory-confirmed data from all cases of IPD in Denmark. From January 1980–June 2013 all children aged 0–15 years with rIPD were identified. Clinical data and data on serotype-specific pneumococcal antibody response were collected. Over the years quantification of pneumococcal antibodies varied from being presented in arbitrary units (ELISA), in μg/ml (WHO ELISA) and lately in μg/ml based on Luminex technology.Results2482 children were diagnosed with IPD and 75 episodes of rIPD were documented in 59 children. An underlying disease was documented in 45 (76%) children. Vaccination data were available for 26 children; 11 were vaccinated solely with PPV23, 8 with a combination of PPV23 + PCV7, 5 with PCV7 and 2 with PCV13. In total, nine responded to PPV23 vaccination and ten were PPV23 non-responders. Of the 15 PCV vaccinated children, two children responded subnormal to PCV7. Among PPV23 non-responders, five responded to subsequent PCV vaccination.ConclusionsIn our population-based study of children with rIPD 53% of the children responded insufficiently to PPV23 vaccination. PPV23 non-responders benefitted from PCV vaccination.