Pneumococcal Infection Research Articles

Impaired IgM Memory B Cell Function Is Common in Coeliac Disease but Conjugate Pneumococcal Vaccination Induces Robust Protective Immunity.

Coeliac disease (CD) is associated with hyposplenism, an acquired impairment of spleen function associated with reduced IgM memory B cells and increased susceptibility to serious pneumococcal infection. Little is known about the immune implications of hyposplenism in CD or the optimal pneumococcal vaccination strategy. In this study, the immune effects of hyposplenism in CD, and the accuracy of screening approaches and protective responses induced by two different pneumococcal vaccines were examined. Active and treated CD cohorts, and healthy and surgically splenectomised controls underwent testing for the presence of Howell-Jolly bodies and pitted red cells, spleen ultrasound, and immune assessment of IgM memory B cell frequency and IgM memory B cell responses to T cell-dependent (TD) or T cell-independent (TI) stimulation. Responses following conjugate (TD) and polysaccharide (TI) pneumococcal vaccination were compared using ELISA and opsonophagocytic assays. Although hyposplenism is rare in treated CD (5.1%), functional B cell defects are common (28-61%) and are not detected by current clinical tests. Conjugate pneumococcal vaccination induced superior and sustained protection against clinically relevant serotypes. Clinical practice guidelines in CD should recommend routine pneumococcal vaccination, ideally with a conjugate vaccine, of all patients in lieu of hyposplenism screening.

Combining antibiotic with anti-TLR2/TLR13 therapy prevents brain pathology in pneumococcal meningitis.

Despite effective antibiotic therapy, brain-destructive inflammation often cannot be avoided in pneumococcal meningitis. The causative signals are mediated predominantly through TLR-recruited myeloid differentiation primary response adaptor 88 (MyD88), as indicated by a dramatic pneumococcal meningitis phenotype of Myd88-/- mice. Because lipoproteins and single-stranded RNA are crucial for recognition of Gram-positive bacteria such as Streptococcus pneumoniae by the host immune system, we comparatively analyzed the disease courses of Myd88-/- and Tlr2-/- Tlr13-/- mice. Their phenotypic resemblance indicated TLR2 and -13 as master sensors of S. pneumoniae in the cerebrospinal fluid. A neutralizing anti-TLR2 antibody (T2.5) and chloroquine (CQ) - the latter applied here as an inhibitor of murine TLR13 and its human ortholog TLR8 - abrogated activation of murine and human primary immune cells exposed to antibiotic-treated S. pneumoniae. The inhibitory effect of the T2.5/CQ cocktail was stronger than that of dexamethasone, the current standard adjunctive drug for pneumococcal meningitis. Accordingly, TLR2/TLR13 blockade concomitant with ceftriaxone application significantly improved the clinical course of pneumococcal meningitis compared with treatment with ceftriaxone alone or in combination with dexamethasone. Our study indicates the importance of murine TLR13 and human TLR8, besides TLR2, in pneumococcal meningitis pathology, and suggests their blockade as a promising antibiotic therapy adjunct.

Lipoprotein signal peptidase-deficient Streptococcus pneumoniae exhibits impaired Toll-like receptor 2-stimulatory activity.

Streptococcus pneumoniae is a causative agent of community-acquired pneumonia. Upon pneumococcal infection, innate immune cells recognize pneumococcal lipoproteins via Toll-like receptor 2and induce inflammation. Here, we generated a strain of S. pneumoniae deficient in lipoprotein signal peptidase (LspA), a transmembrane type II signal peptidase required for lipoprotein maturation, to investigate the host immune response against this strain. Triton X-114 phase separation revealed that lipoprotein expression was lower in the LspA-deficient strain than in the wild-type strain. Additionally, the LspA-deficient strain decreased nuclear factor-κB activation and cytokine production in THP-1 cells, indicating impaired innate immune response against the strain.

Immunological aspects of vaccination in HIV-infected patients

Until recently, HIV infection does not lose its relevance. In 2022, 630 000 people died and 1.3 million people became infected with the human immunodeficiency virus (HIV). HIV-positive persons develop more infectious diseases than healthy people do; the causative agents are mainly opportunistic microorganisms. Streptococcus pneumoniae is the main causative agent of infection in the lungs in HIV-infected persons. In order to prevent the development of severe pneumococcal infections and to overcome antibiotic resistance, vaccines have been developed. There are polysaccharide (PPV) and conjugate (PCV) vaccines. According to clinical recommendations, vaccination of previously unvaccinated HIV-infected patients is carried out regardless of T-helper cell level. However, no data were found on the effect of PCV13 on immunological memory cells. The purpose of this study is to assess an effect of PCV13 vaccination on the immune system in HIV-infected subjects.
 Materials and methods. The study included 200 patients with HIV infection, which were divided into two groups: I — received a dose of PCV13 (n = 100) and control group (n = 100). During the first visit, immunological and microbiological studies were carried out. On the second visit, a PCV13 was injected into the deltoid muscle. The third visit was made a year later, where immunological and microbiological studies were repeated. Participants were divided into 4 subgroups depending on CD4+ T cell level. The microbial study was done using a swab collected from the back of the throat.
 Results. During the immunological examination at visit 1, abnormalities were detected in all examined populations and immune cell subsets. At 12 months post-vaccination, the median levels of CD3+CD4+ and CD45RO+ T lymphocytes in the immunized group were higher than pre-vaccination levels compared to control group, in which the values changed insignificantly. Our data confirm the immunological effectiveness of PCV13 administration in HIV-infected patients. In patients with peripheral blood CD19+ lymphocyte deficiency, had increased microbial detection rate (p = 0.003).
 Conclusion. As a result, due to the high risk of pneumococcal pneumonia, HIV-infected patients should be immunized with a 13-valent pneumococcal conjugate vaccine.

Impact of direct ICU admission of pneumococcal meningitis in France: a retrospective analysis of a French medico-administrative (PMSI) database

BackgroundCurrent guidelines for adult patients with pneumococcal meningitis (PM) recommend initial management in intermediate or intensive care units (ICU), but evidence to support these recommendations is limited. We aimed to describe ICU admission practices of patients with PM.MethodsWe conducted a retrospective analysis of the French medico administrative database of consecutive adult patients with PM and sepsis criteria hospitalized between 2011 and 2020. We defined two groups, “Direct ICU” corresponding to a direct ICU admission and “Delayed ICU” corresponding to a secondary ICU admission.ResultsWe identified 4052 patients hospitalized for a first episode of PM, including 2006 “Direct ICU” patients (50%) and 2046 “delayed ICU” patients (50%). The patients were mainly males [n = 2260 (56%)] with median age of 61 years [IQR 50–71] and a median Charlson index of 1 [0–3]. Among them, median SAPS II on admission was 46 [33–62], 2173 (54%) had a neurological failure on admission with 2133 (53%) in coma, 654 (16%) with brainstem failure, 488 (12%) with seizures and 779 (19%) with focal signs without coma. PM was frequently associated with pneumonia [n = 1411 (35%)], and less frequently with endocarditis [n = 317 (8%)]. The median ICU length of stay and hospital length of stay were 6 days [2–14] and 21 days [13–38], respectively. In-hospital mortality was 27% (n = 1100) and 640 (16%) patients were secondarily transferred to rehabilitation care unit. Direct ICU group was significantly more severe but after adjustment for age, sex, comorbidities, organ failures on admission and admission from home, direct ICU admission was significantly associated with a lower mortality (Odds ratio 0.67 [0.56–0.80], p < 0.01). This corresponded to one death avoided for 11 PM directly admitted in ICU.ConclusionsAmong patients with PM and sepsis, direct ICU admission was associated with lower mortality rates when compared to delayed admission.

Robust Immune Response and Protection against Lethal Pneumococcal Challenge with a Recombinant BCG-PspA-PdT Prime/Boost Scheme Administered to Neonatal Mice.

Pneumococcal diseases are an important public health problem, with high mortality rates in young children. Although conjugated pneumococcal vaccines offer high protection against invasive pneumococcal diseases, this is restricted to vaccine serotypes, leading to serotype replacement. Furthermore, the current vaccines do not protect neonates. Therefore, several protein-based pneumococcal vaccines have been studied over the last few decades. Our group established a recombinant BCG expressing rPspA-PdT as a prime/rPspA-PdT boost strategy, which protected adult mice against lethal intranasal pneumococcal challenge. Here, we immunized groups of neonate C57/Bl6 mice (6-10) (at 5 days) with rBCG PspA-PdT and a boost with rPspA-PdT (at 12 days). Controls were saline or each antigen alone. The prime/boost strategy promoted an IgG1 to IgG2c isotype shift compared to protein alone. Furthermore, there was an increase in specific memory cells (T and B lymphocytes) and higher cytokine production (IFN-γ, IL-17, TNF-α, IL-10, and IL-6). Immunization with rBCG PspA-PdT/rPspA-PdT showed 100% protection against pulmonary challenge with the WU2 pneumococcal strain; two doses of rPspA-PdT showed non-significant protection in the neonates. These results demonstrate that a prime/boost strategy using rBCG PspA-PdT/rPspA-PdT is effective in protecting neonates against lethal pneumococcal infection via the induction of strong antibody and cytokine responses.

In Silico Identification and Characterization of Drug Targets in Streptococcus pneumoniae ATCC 700669 (Serotype 23F) by Subtractive Genomics.

Streptococcus pneumoniae (S. pneumoniae) is an important pathogen worldwide that causes pneumococcal infections which are related to high rates of morbidity and mortality especially in young children, older adults, and immune-compromised persons. Antibiotic resistance in S. pneumoniae is a serious problem across the world from time to time, resulting in treatment failure and diminished value of older medicines. Therefore, the objective of this study was to identify new putative drug targets against S. pneumoniae serotype 23F by using subtractive genomics. By using bioinformatics tools such as NCBI, UniProt KB, PDB, KEGG, DEG, PSORTb, CD hit, DrugBank database, and other softwares, proteins involved in unique metabolic pathways of S. pneumoniae serotype 23F were studied. The result indicates that this serotype consists of 97 metabolic pathways of which 74 are common with that of human, and 23 pathways are unique to the serotype 23F. After investigation and analysis of essentiality, nonhomology, subcellular localization, having drug targets, and enzymatic activity, four proteins were prioritized as druggable targets. These druggable proteins include UDP-N-acetylglucosamine 1-carboxyvinyltransferase, UDP-N-acetyl muramate dehydrogenase, D-alanine-D-alanine ligase, and alanine racemase that are found in S. pneumoniae serotype 23F. All these four proteins are essential, are nonhomologous with human proteins, have drug targets, and are located in cell cytoplasm. Therefore, the authors recommend these proteins to be used for efficient drug design against S. pneumoniae serotype 23F after experimental validation for essentiality and druggability.

Increased Risk of Long-Term Disabilities Following Childhood Bacterial Meningitis in Sweden

Few studies have examined the incidence of long-term disabilities due to bacterial meningitis in childhood with extended follow-up time and a nationwide cohort. To describe the long-term risks of disabilities following a childhood diagnosis of bacterial meningitis in Sweden. This nationwide retrospective registry-based cohort study included individuals diagnosed with bacterial meningitis (younger than 18 years) and general population controls matched (1:9) by age, sex, and place of residence. Data were retrieved from the Swedish National Patient Register from January 1, 1987, to December 31, 2021. Data were analyzed from July 13, 2022, to November 30, 2023. A diagnosis of bacterial meningitis in childhood recorded in the National Patient Register between 1987 and 2021. Cumulative incidence of 7 disabilities (cognitive disabilities, seizures, hearing loss, motor function disorders, visual disturbances, behavioral and emotional disorders, and intracranial structural injuries) after bacterial meningitis in childhood. The cohort included 3623 individuals diagnosed with bacterial meningitis during childhood and 32 607 controls from the general population (median age at diagnosis, 1.5 [IQR, 0.4-6.2] years; 44.2% female and 55.8% male, median follow-up time, 23.7 [IQR, 12.2-30.4] years). Individuals diagnosed with bacterial meningitis had higher cumulative incidence of all 7 disabilities, and 1052 (29.0%) had at least 1 disability. The highest absolute risk of disabilities was found for behavioral and emotional disorders, hearing loss, and visual disturbances. The estimated adjusted hazard ratios (HRs) showed a significant increased relative risk for cases compared with controls for all 7 disabilities, with the largest adjusted HRs for intracranial structural injuries (26.04 [95% CI, 15.50-43.74]), hearing loss (7.90 [95% CI, 6.68-9.33]), and motor function disorders (4.65 [95% CI, 3.72-5.80]). The adjusted HRs for cognitive disabilities, seizures, hearing loss, and motor function disorders were significantly higher for Streptococcus pneumoniae infection (eg, 7.89 [95% CI, 5.18-12.02] for seizure) compared with Haemophilus influenzae infection (2.46 [95% CI, 1.63-3.70]) or Neisseria meningitidis infection (1.38 [95% CI, 0.65-2.93]). The adjusted HRs for cognitive disabilities, seizures, behavioral and emotional disorders, and intracranial structural injuries were significantly higher for children diagnosed with bacterial meningitis at an age below the median. The findings of this cohort study of individuals diagnosed with bacterial meningitis during childhood suggest that exposed individuals may have had an increased risk for long-term disabilities (particularly when diagnosed with pneumococcal meningitis or when diagnosed at a young age), highlighting the need to detect disabilities among surviving children.

Hypidone hydrochloride (YL-0919) protects mice from meningitis via Sigma1R-STAT1-NLRP3-GSDMD pathway

BackgroundA growing number of studies have found that antidepressants have anti-inflammatory effects while protecting nerves. Hypidone hydrochloride (YL-0919) is a novel highly selective 5-HT reuptake blocker. Our previous studies have demonstrated that YL-0919 exerts notable antidepressant- and anxiolytic-like as well as procognitive effects. However, whether YL-0919 can be used to treat inflammatory and infectious diseases remain unknown. In this study, we aimed to verify the anti-inflammatory effect of YL-0919 on bacterial meningitis and further explore the potential molecular mechanisms. MethodsWe performed the experiments on pneumococcal meningitis mice in vivo and S. pneumoniae infected macrophages/microglia in vitro, with or without YL-0919 treatment.Cognitive function was evaluated by open-field task, Morris water maze test, and novel object recognition test. Histopathological staining and immunofluorescence staining were used to detect the pathological damage of meningitis and NLRP3 inflammasome activation in microglia/macrophages. The expression of the STAT1/NLRP3/GSDMD signal pathway was measured by western blots. Proinflammatory cytokines associated with pyroptosis were detected by ELISA. ResultsYL-0919 protected mice from fatal pneumococcal meningitis, characterized by attenuated cytokine storms, decreased bacterial loads, improved neuroethology, and reduced mortality. NLRP3 plays a key role in the regulation of inflammation. When the underlying mechanisms were investigated, we found that YL-0919 inhibited the activation of NLRP3 via STAT1, and thus inhibited macrophages/microglia pyroptosis, resulting in downregulation of proinflammatory cytokines. In addition, Sigma1R was identified as a pivotal receptor that can be engaged by YL-0919 to inhibit NLRP3 activation and pyroptosis pathway in microglia/macrophages. ConclusionsThese results provide new insights into the mechanisms of inflammation regulation mediated by the antidepressant YL-0919. Moreover, targeting the STAT1/NLRP3 pyroptosis pathway is a promising strategy for the treatment of infectious diseases like bacterial meningitis.

Influence of vaccine prevention on the spread and serotype composition of &lt;i&gt;Streptococcus pneumoniae&lt;/i&gt; in military collectives

Objective. Study of the effect of vaccination against pneumococcal infection on the prevalence and serotype composition of S. pneumoniae in military personnel.Materials and methods. The study was conducted among 369 military personnel of the military unit of the Sverdlovsk region. Determination of the frequency and serotype of S. pneumoniae was carried out upon admission and after 1.5 months of stay in the military collective using the multiplex PCR method.Results. After 1.5 months of stay of servicemen in the military collective, a significant activation of pneumococcal circulation was established (χ2McNemar=24.038; p0.001). The risk of S. pneumoniae infection among unvaccinated military personnel was 1.39 times higher compared to vaccinated military personnel (RR=1.39; 95% CI 1.209–1.596). In the group of unvaccinated military personnel, the frequency of occurrence of vaccine serotypes was 2.6 times higher than in vaccinated ones (χ2 = 6.25; p = 0.01).Conclusions. The proactive influence of immunization against pneumococcal infection on the prevalence and serotype landscape of S. pneumoniae has been established: A low prevalence of vaccine serotypes and a predominance of non-typeable serotypes have been revealed among vaccinated individuals.

Retrospective database analysis for clinical diagnoses commonly associated with pneumococcal diseases in the Malaysian healthcare system over a 3-year period (2013–2015)

BackgroundPneumococcal disease caused by Streptococcus pneumoniae is an important cause of morbidity and mortality across all ages, particularly in younger children and older adults. Here, we describe pneumococcal disease hospitalizations at Ministry of Health (MoH) facilities in Malaysia between 2013 and 2015.MethodsThis was a retrospective databases analysis. Tabular data from the Malaysian Health Data Warehouse (MyHDW) were used to identify microbiologically confirmed, pneumococcal disease hospitalizations and deaths during hospitalization, using hospital-assigned ICD-10 codes (i.e., classified as meningitis, pneumonia, or non-meningitis non-pneumonia). Case counts, mortality counts, and case fatality rates were reported by patient age group and by Malaysian geographic region.ResultsA total of 683 pneumococcal disease hospitalizations were identified from the analysis: 53 pneumococcal meningitis hospitalizations (5 deaths and 48 discharges), 413 pneumococcal pneumonia hospitalizations (24 deaths and 389 discharges), and 205 non-meningitis non-pneumonia pneumococcal disease hospitalizations (58 deaths and 147 discharges). Most hospitalizations occurred in children aged < 2 years. Crude mortality was highest among children aged < 2 years (for all three disease categories), among adults aged ≥ 65 years (for pneumococcal pneumonia), or among adults aged 65–85 years (for non-meningitis non-pneumonia pneumococcal disease). The case fatality rate, all ages included, was 5.8% for pneumococcal pneumonia, 9.1% for pneumococcal meningitis, and 28.3% for non-meningitis non-pneumonia pneumococcal disease.ConclusionsOur study is the first to document pneumococcal disease hospitalizations and deaths during hospitalization in Malaysia. Although this database analysis likely underestimated case counts, and the true disease burden could be even greater, the study demonstrates a substantial burden of pneumococcal disease. Public health measures, including vaccination, would significantly contribute to the prevention of hospitalizations and deaths associated with pneumococcal disease in Malaysia.

Immunomodulation of susceptibility to pneumococcal pneumonia infection in mouse lungs exposed to carbon nanoparticles via dysregulation of innate and adaptive immune responses

Carbon nanotubes (CNTs) are emerging pollutants of occupational and environmental health concern. While toxicological mechanisms of CNTs are emerging, there is paucity of information on their modulatory effects on susceptibility to infections. Here, we investigated cellular and molecular events underlying the effect of multi-walled CNT (MWCNT) exposure on susceptibility to Streptococcus pneumoniae infection in our 28-day sub-chronic exposure mouse model. Data indicated reduced phagocytic function in alveolar macrophages (AMs) from MWCNT-exposed lungs evidenced by lower pathogen uptake in 1-h infection assay. At 24-h post-infection, intracellular pathogen count in exposed AMs showed 2.5 times higher net increase (2-fold in vehicle- versus 5-fold in MWCNT-treated), indicating a greater rate of intracellular multiplication and/or survival due to MWCNT exposure. AMs from MWCNT-exposed lungs exhibited downregulation of pathogen-uptake receptors CD163, Phosphatidyl-serine receptor (Ptdsr), and Macrophage scavenger receptors class A type 1 (Msr1) and type 2 (MSr2). In whole lung, MWCNT exposure shifted the macrophage polarization state towards the immunosuppressive phenotype M2b and increased the CD11c+ dendritic cell population required to activate the adaptive immune response. Notably, the MWCNT pre-exposure dysregulated T-cell immunity, evidenced by diminished CD4 and Th17 response, and exacerbated Th1 and Treg responses (skewed Th17/Treg ratio), thereby favoring the pneumococcal infection. Overall, these findings indicated that MWCNT exposure compromises both innate and adaptive immunity leading to diminished host lung defense against pneumonia infection. To our knowledge, this is the first report on an immunomodulatory role of CNT pre-exposure on pneumococcal infection susceptibility due to dysregulation of both innate and adaptive immunity targets.

Evaluation of Acute and Convalescent Antibody Concentration Against Pneumococcal Capsular Polysaccharides for the Diagnosis of Pneumococcal Infection in Children with Community-Acquired Pneumonia.

We evaluated whether the quantification of IgG to pneumococcal capsular polysaccharides is an accurate diagnostic test for pneumococcal infection in children with pneumonia in Nepal. Children with pneumococcal pneumonia did not have higher convalescent, or higher fold change, IgG to pneumococcal polysaccharides than children with other causes of pneumonia. Caution is needed in interpreting antibody responses in pneumococcal infections.

Association of respiratory infections and the impact of vaccinations on cardiovascular diseases.

Influenza, pneumococcal, severe acute respiratory syndrome coronavirus 2, and respiratory syncytial virus infections are important causes of high morbidity and mortality in the elderly. Beyond the burden of infectious diseases, they are also associated with several non-infectious complications like cardiovascular events. A growing body of evidence in prospective studies and meta-analyses has shown the impact of influenza and pneumococcal vaccines on types of cardiovascular outcomes in the general population. Influenza vaccination showed a potential benefit for primary and secondary prevention of cardiovascular diseases across all ages. A reduced risk of cardiovascular events for individuals aged 65 years and older was associated with pneumococcal vaccination. Despite scientific evidence on the effectiveness, safety, and benefits of the vaccines and recommendations to vaccinate elderly patients and those with risk factors, vaccination rates remain sub-optimal in this population. Doubts about vaccine necessity or efficacy and concerns about possible adverse events in patients and physicians refer to delayed acceptance. Vaccination campaigns targeting increasing professional recommendations and public perceptions should be implemented in the coming years. The aim of this review paper is to summarize the effect of vaccination in the field of cardiovascular disease to achieve a higher vaccination rate in this patient population.

Purpura fulminans – meningococcal infection or postsplenectomy sepsis

The article presents two clinical cases with description of peculiarities of septic infection occurred after splenectomy and due to congenital splenic hypoplasia.Decreased immune defense resulted from splenectomy leads to severe infections with a high risk of death. The most severe sequela is overwhelming postsplenectomy infection (OPSI-syndrome) which is characterized by high mortality rate (50-70%) within 12-24 hours from the onset of the first symptoms. The main risk factors of postsplenectomy sepsis are a condition which became an indication for splenectomy, the immune status of the patient, age and the time period after splenectomyStreptococcus pneumoniae, Haemophilus infuenzae type b, Neisseria meningitidis are commonly identified etiological factors of OPSI-syndrome. The diagnosis could be delayed due to nonspecific flu-like prodromal symptoms of the OPSI-syndrome. Delay in the diagnosis and treatment of sepsis may increase the risk of death.One of the syndromes associated with post-splenectomy sepsis is fulminant purpura (purpura fulminans), which requires differential diagnosis with meningococcal infection. However, half of the cases of fulminant pneumococcal purpura occur in patients with asplenia or hyposplenia. In the first clinical case, a preliminary diagnosis of generalized meningococcal infection was made on admission, but the diagnosis of pneumococcal infection could not be excluded in asplenic patient and was subsequently confirmed by laboratory tests.Given the high risk of fulminant postsplenectomy sepsis, and the difficulties of timely diagnosis, the preventive strategy of infections after splenectomy falls into three major categories- vaccination, antibiotic prophylaxis, and patient (patient’s parents) education.Improving healthcare workers’ knowledge is required to ensure prompt diagnosis of hyposplenism, adequate risk assessment of postplenectomy infection and prevention of OPSI-syndrome.

Characterization of chicken-derived antibody against Alpha-Enolase of Streptococcus pneumoniae

Streptococcus pneumoniae is a clinically relevant pathogen notorious for causing pneumonia, meningitis, and otitis media in immunocompromised patients. Currently, antibiotic therapy is the most efficient treatment for fighting pneumococcal infections. However, an arise in antimicrobial resistance in S. pneumoniae has become a serious health issue globally. To resolve the problem, alternative and cost-effective strategies, such as monoclonal antibody-based targeted therapy, are needed for combating bacterial infection. S. pneumoniae alpha-enolase (spEno1), which is thought to be a great target, is a surface protein that binds and converts human plasminogen to plasmin, leading to accelerated bacterial infections. We first purified recombinant spEno1 protein for chicken immunization to generate specific IgY antibodies. We next constructed two single-chain variable fragments (scFv) antibody libraries by phage display technology, containing 7.2 × 107 and 4.8 × 107 transformants. After bio-panning, ten scFv antibodies were obtained, and their binding activities to spEno1 were evaluated on ELISA, Western blot and IFA. The epitopes of spEno1 were identified by these scFv antibodies, which binding affinities were determined by competitive ELISA. Moreover, inhibition assay displayed that the scFv antibodies effectively inhibit the binding between spEno1 and human plasminogen. Overall, the results suggested that these scFv antibodies have the potential to serve as an immunotherapeutic drug against S. pneumoniae infections.

Distinct baseline immune characteristics associated with responses to conjugated and unconjugated pneumococcal polysaccharide vaccines in older adults

Pneumococcal infections cause serious illness and death among older adults. The capsular polysaccharide vaccine PPSV23 and conjugated alternative PCV13 can prevent these infections; yet, underlying immunological responses and baseline predictors remain unknown. We vaccinated 39 older adults (>60 years) with PPSV23 or PCV13 and observed comparable antibody responses (day 28) and plasmablast transcriptional responses (day 10); however, the baseline predictors were distinct. Analyses of baseline flow cytometry and bulk and single-cell RNA-sequencing data revealed a baseline phenotype specifically associated with weaker PCV13 responses, which was characterized by increased expression of cytotoxicity-associated genes, increased frequencies of CD16+ natural killer cells and interleukin-17-producing helper T cells and a decreased frequency of type 1 helper T cells. Men displayed this phenotype more robustly and mounted weaker PCV13 responses than women. Baseline expression levels of a distinct gene set predicted PPSV23 responses. This pneumococcal precision vaccinology study in older adults uncovered distinct baseline predictors that might transform vaccination strategies and initiate novel interventions.

Влияние вакцинации против гриппа, пневмококковой инфекции и SARS-CoV-2 на заболеваемость и тяжесть течения COVID‑19 у медицинских работников отдельного учреждения (эпидемиологические исследования)

Objective. To study the effect of influenza, pneumococcal and SARS-CoV-2 vaccination on the incidence and severity of COVID-19 course in health care workers. Patients and Methods. We examined 547 health care workers divided into group 1 (no history of influenza and pneumococcal vaccination, n = 281) and groups vaccinated between August and October 2020 (before SARS-CoV-2 epidemic II): Group 2 against influenza (n = 98), Group 3 against pneumococcal infection (n = 60), and Group 4 against influenza and pneumococcus (n = 108). Between March and August 2021 (before the SARS-CoV-2 epidemic III outbreak), 98.6% of all employees were vaccinated against COVID-19. We compared COVID-19 incidence rates during Periods II and III epidemic rises (2020–2022) as a function of influenza and pneumococcal vaccination. Results. It was found that with combined vaccination against influenza and pneumococcal infection in the group of medical workers at high risk of infection, the risk of COVID-19 morbidity within 4–5 months was 2 times lower (1.6% vs. 13.2%, p &lt; 0.05) compared to the unvaccinated. Comparative data on COVID-19 incidence in the II and III periods of epidemic rises showed that COVID-19 in medical workers in the III period was registered 36.1% lower in comparison with the index in the II period – 11.2 and 7.1%, respectively (p &lt; 0.05). We found that when comparing II and III periods of epidemic rises among medical workers, the proportion of persons with COVID-19 with moderate forms of disease who received combined vaccination against influenza and pneumococcal infection decreases more than 2-fold (p &lt; 0.05), including in the category with a high risk of infection. Conclusion. The presented data indicate a positive effect of combined vaccination against pneumococcal infection and influenza on the incidence and severity of COVID-19. The proposed approach can be used in public health practice as a method of nonspecific prevention of COVID-19 and other acute respiratory viral infections. Key words: influenza vaccine, pneumococcal vaccine, combined vaccination, epidemic rise, COVID-19

IL-10-Mediated Regulation of Microglial Inflammation in Brain Meningitis: Novel Insights and Therapeutic Potential.

Inflammation is a key pathological process in bacterial meningitis, and the transforming growth factor-beta-activated kinase 1 (TAK1)/nuclear factor-kappa B (NF-κB) pathway is implicated in the activation of microglia and the production of inflammatory factors. Interleukin (IL)-10 is an anti-inflammatory cytokine acting in an autocrine fashion in macrophages to limit inflammatory responses by decreasing the production of pro-inflammatory cytokines. This paper investigates how IL-10 can inhibit microglia activation and reduce the inflammatory response of nervous system diseases. This study used a pneumococcal-induced in Pneumococcal meningitis (PM) C57BL/6 mice and BV-2 cells model of microglial activation, assessing the effects of IL-10 on the TAK1/NF-κB pathway. The impact of IL-10 on microglial autophagy was investigated through western blot and immunofluorescence. The effects of IL-10 were evaluated by examining cellular activation markers and the activity of molecular signaling pathways (such as phosphorylation levels of TAK1 and NF-κB). Pneumococcus induced the activation of microglia and reduced IL-10. IL-10 inhibited the TAK1/NF-κB pathway, reducing the pneumococcal-induced inflammatory response in microglia. IL-10 ameliorated pneumococcal infection-induced microglial injury by inhibiting autophagy. Animal experiment results also showed that IL-10 inhibited inflammation and autophagy during Pneumococcal meningitis in mice. Our study demonstrates that IL-10 reduces the inflammatory response of microglia by inhibiting the TAK1/NF-κB pathway. Additionally, IL-10 ameliorates pneumococcal infection-induced microglial injury by inhibiting the process of autophagy. These results provide a new theoretical basis and offer new insights for developing strategies to treat bacterial meningitis.

Bacteremia and meningitis caused by penicillin-resistant Streptococcus pneumoniae serotype 35B successfully treated with ceftriaxone combined with vancomycin followed by linezolid: A case report.

We herein report a case of bacterial meningitis and bacteremia in a 3-month-old boy caused by Streptococcus pneumoniae serotype 35B multidrug resistance. Intravenous ampicillin was administered on admission. However, when pneumococcal meningitis was suspected, the antibiotic treatment was changed to ceftriaxone (CTRX) and vancomycin (VCM). However, owing to difficulties in achieving sufficient serum trough levels of VCM, this treatment was again switched to linezolid (LZD). The patient recovered without complications after 16 days of CTRX and LZD treatment. This case suggests that LZD is a viable treatment option for bacterial meningitis.