Search Results (57)

Purpose: This study aimed to evaluate the immunological response to the 23-valent pneumococcal polysaccharide vaccine (PPV23) in patients investigated for immunodeficiencies due to recurrent infections at EPM-UNIFESP Clinical Immunology outpatient clinic. Methods: This is a longitudinal retrospective study. Data were collected from the medical records of patients between 2012 and 2020. The analyses were developed in two stages: before and after administration of the PPV23 vaccine. Results: A total of 390 patients who received the PPV23 vaccine were selected. Among those who demonstrated an adequate serological response (63.6%), there was a notable decrease in the risk of upper respiratory tract infections (URTI) by 66%, tonsillitis by 74%, otitis by 76%, sinusitis by 49%, and uncomplicated pneumonia (PNM) by 77%. For invasive infections, the risk reduction was 95% for pneumonia with parapneumonic effusion and 93% for meningitis. Conclusions: The study demonstrated a significant decrease in the risk of bacterial infections following the administration of the PPV23 vaccine in this population. Therefore, we recommend including PPV23 in the vaccination schedule following pneumococcal conjugated vaccines for patients with recurrent pneumococcal infections to enhance protection and avoid complications. Full article

Background: The introduction of biological drugs into clinical practice for the treatment of children with systemic juvenile idiopathic arthritis (sJIA) allows disease control but increases the risk of infectious events. Infectious events cause immunosuppressive therapy interruptions, leading to disease flare and life-threatening complications, namely macrophage activation syndrome. Our study aimed to evaluate the efficacy and safety of simultaneous vaccination against pneumococcal and Haemophilus influenzae type b (Hib) in children with sJIA. Methods: This study included 100 sJIA patients receiving immunosuppressive therapy who were simultaneously vaccinated against pneumococcal and Haemophilus influenzae type b (Hib) infections. The mean age of disease onset was 5.5 years. The median age at vaccination was 10 ± 4.5 years. Clinical and laboratory parameters of sJIA activity, immunization efficacy, and safety, including anti-SP and anti-Hib IgG antibodies, as well as all vaccination-related adverse events (AEs), were recorded in every patient before, 3 weeks after, and 6 months after vaccination. Results: At the time of vaccination, 29% of patients did not meet the criteria for the inactive disease stage, as defined by C. Wallace: active joints were present in 34.5% of patients, systemic manifestations (rash and/or fever) were present in 41.3%, and 24.2% of patients had solely inflammatory laboratory activity. The protective titer of anti-SP and anti-Hib IgG antibodies was detected in the majority of patients 3 weeks after vaccination (100% and 93%, respectively). The results remained unchanged (99% and 92%, respectively) for 6 months of follow-up, compared to the baseline (91% and 37%, p = 0.000001). Anti-SP IgG and anti-Hib titers raised from 48.3 (18.2; 76.5) and 0.64 (0.3; 3.2) U/mL at the baseline to 103.5 (47.3; 185.4) and 4 (3.5; 4.2) U/mL at D22 and 105 (48.7; 171.8) and 4 (3.8; 4) U/mL (EOS), respectively. Immunosuppressive therapy regimens (combined therapy or biological disease-modifying antirheumatic drug monotherapy) did not influence the immunogenic efficacy of vaccination. The incidence of infectious complications (p = 0.0000001) and antibiotic prescriptions (p = 0.0000001) decreased by more than two times, to 29.9 and 13.8 events per 100 patient months, respectively, within 6 months after vaccination—the average duration of acute infectious events was reduced by five times after immunization (p = 0.0000001). Vaccination did not lead to disease flare: the number of patients with active joints decreased by half compared to the baseline, and the number of patients with systemic manifestations decreased by six times. All vaccine-associated adverse events were considered mild and resolved within 1–2 days. Conclusions: Simultaneous vaccination against pneumococcal and Hib infections in sJIA children is an effective and safe tool that reduces the number and duration of infectious events and does not cause disease flare-ups. Full article

Background: The aging of the population has increased the number of frail people living in long-term care facilities, underscoring the need for continuous updates in infectious diseases prevention strategies. The aim of this study was to analyze two pneumococcal disease outbreaks in elderly residences in Gipuzkoa, northern Spain, their impact on residents, and the containment measures implemented. Material and methods: The outbreaks took place in 2023 and in 2024 in two residences of 111 and of 155 residents, respectively. Diagnosis was based on clinical criteria, radiological findings, and microbiological techniques. Pneumococcal isolates were characterized by whole-genome sequencing. Results: The outbreaks involved five and six residents, respectively. Most residents in both facilities had been vaccinated with the pneumococcal polysaccharide 23-valent vaccine (PPV23) more than five years prior. The median attack rates were 4.5% and 3.9%, lower than those reported in similar outbreaks. The adopted infection transmission prevention measures successfully limited the spread of the outbreaks. Conclusions: PPV23 vaccination did not prevent invasive pneumococcal infection in the affected residents. The vaccination of elderly people living in long-term care facilities with 20-valent and 21-valent pneumococcal conjugated vaccines should be evaluated as a new preventive measure. Full article

Background/Objectives: The clinical impact of replacing the 23-valent pneumococcal polysaccharide vaccine (PPSV23) for the vaccination of older (≥60 years) and at-risk German adults with either the 20-valent (PCV20) or 21-valent (V116) pneumococcal conjugate vaccine (PCV) was evaluated. Methods: An age- and serotype-specific transmission model was adapted to Germany to evaluate the impact of V116 versus PCV20 vaccination on pneumococcal disease (PD) incidence, including invasive pneumococcal disease (IPD) and inpatient and outpatient non-bacteremic pneumococcal pneumonia, over 10 years. A reference strategy (PPSV23 vaccination at a constant 30% vaccine coverage rate (VCR)) was compared against eight strategies varying by PCV (PCV20 vs. V116), VCR (30% vs. 60%), with or without the PCV revaccination of previously PPSV23-vaccinated adults (0% vs. 50% revaccination). Results: Vaccination with PCV20 and V116 initially decreased PD incidence, but incidence returned to pre-vaccine levels after five and eight years, respectively. Increasing the VCR to 60% prevented this resurgence. At a 10-year time horizon, V116 with 30% VCR reduced IPD cases by 9%, inpatient NBPP cases by 10%, and outpatient NBPP cases by 7% compared to the reference strategy. PCV20 with 30% VCR reduced these cases by 6%, 5%, and 4%, respectively. Increasing the VCR to 60% and revaccinating 50% of previously PPSV23-vaccinated adults further reduced IPD cases by 14% and 13% for V116, and by 9% and 9% for PCV20. Conclusions: Increasing the vaccination coverage rate to 60% and strategically revaccinating previously PPSV23-vaccinated adults significantly enhanced the effectiveness of pneumococcal vaccines, with V116 showing greater overall reductions in disease incidence compared to PCV20 or PPSV23. Full article

Background: V116 is a 21-valent pneumococcal conjugate vaccine (PCV) designed for adults. It contains the most prevalent serotypes associated with invasive pneumococcal disease (IPD) in adults in regions with established pediatric vaccination programs. This Phase 3 study compared the safety, tolerability, and immunogenicity of V116 with 23-valent pneumococcal polysaccharide vaccine (PPSV23) in adults ≥50 years of age. Methods: In this randomized, active comparator-controlled, parallel-group, multisite, double-blind study, participants were randomized 1:1 to receive a single dose of V116 or PPSV23 (NCT05569954). Primary immunogenicity outcomes assessed the opsonophagocytic activity (OPA) responses for (i) non-inferiority for 12 serotypes common to V116 and PPSV23 based on V116/PPSV23 geometric mean titers (GMTs) at Day 30, and (ii) superiority for nine serotypes unique to V116 using V116/PPSV23 GMTs and the proportions of participants with a ≥4-fold rise in OPA responses from baseline to 30 days post-vaccination. The primary safety outcome was evaluated as the proportion of participants with solicited injection-site and systemic adverse events through Day 5 post-vaccination, and vaccine-related serious adverse events up to 6 months post-vaccination. Findings: V116 was non-inferior to PPSV23 for all 12 common serotypes, superior to PPSV23 for all nine unique serotypes based on V116/PPSV23 GMTs, and superior to PPSV23 for eight of the nine serotypes unique to V116, based on the proportion of participants with a ≥4-fold rise in OPA responses (except for serotype 15C). The safety profile of V116 was comparable to that of PPSV23. Interpretation: In regions with established vaccination programs, V116 could broaden the serotype coverage for residual pneumococcal disease in adults. Full article

Background/Objectives: Streptococcus pneumoniae with, or following, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been associated with increased mortality, particularly in older adults. However, vaccination can be an effective preventative measure. This Phase 3 study (NCT05158140) assessed the immunogenicity and safety of co-administering the SARS-CoV-2 vaccine mRNA-1273 with the 23-valent pneumococcal polysaccharide vaccine (PPSV23) or the 15-valent pneumococcal conjugate vaccine (PCV15). Methods: Participants were healthy adults ≥50 years of age who had previously received a two-dose primary series of mRNA-1273 ≥5 months before the first study visit and may have received a booster dose of mRNA-1273 ≥4 months prior to the first study visit. Participants were randomized (1:1:1:1) to receive mRNA-1273 concomitantly with PPSV23 or PCV15 on Day 1 followed by placebo on Day 30, or sequentially with mRNA-1273 and placebo on Day 1 and PPSV23 or PCV15 on Day 30. The primary study endpoints were pneumococcal-serotype-specific opsonophagocytic activity (OPA) geometric mean titers (GMTs) and SARS-CoV-2-specific binding antibody GMTs at 30 days after vaccination, as well as safety and tolerability following vaccination. Results: In total, 850 adults participated in the study. Serotype-specific OPA GMTs at 30 days post-vaccination with PPSV23 or PCV15 were generally comparable between the concomitant and sequential groups. SARS-CoV-2-specific GMTs increased in all groups from pre-vaccination to 30 days post-vaccination with mRNA-1273, with a consistent response between concomitant and sequential groups. Safety profiles were comparable across study groups. Conclusions: Co-administration of mRNA-1273 with PPSV23 or PCV15 in healthy adults ≥50 years of age was immunogenic and well tolerated. Full article

Background: Immunosuppressive therapy (methotrexate and biological agents) for juvenile idiopathic arthritis (JIA) is associated with an increased risk of severe infections, higher infection rates, treatment interruptions, failure to achieve disease remission, and recurrent disease flares. Our study aimed to evaluate the safety and efficacy of simultaneous immunization with 13-valent polysaccharide conjugate vaccines (PCV13) against S. pneumoniae (SP) and Hemophilus influanzae type b infections (HibV) in children with JIA without systemic manifestations. Methods: A total of 371 non-systemic JIA patients who received 13PCV and HibV were included in this prospective cohort study. In every patient, we evaluated clinical, laboratory, anti-SP, and anti-Hib IgG antibodies before vaccination, three weeks after, and six months after, and all adverse events (AEs) were collected during the study. The number and duration of acute respiratory infection (ARI) episodes and requirements for antibacterial treatment and AE six months before and after the baseline were collected. Results: The levels of the Ig G anti-SP and anti-Hib antibodies increased in the 3 weeks after vaccination; then, anti-SP antibodies slightly decreased and anti-Hib antibodies remained increased during the whole study, as well as in a part of the patients with a protective titer. During the study, there were no patients with significant flares, and the main JIA outcomes gradually decreased during the trial. The number of patients with uveitis remained equal, as well as the part of the patients with active, low-active, and inactive uveitis. There was no significant rise in the hs-CRP or S100 protein after the vaccination. Previous or ongoing treatment with non-biological (p = 0.072) and biological (p = 0.019) disease-modified anti-rheumatic drugs affected the Hib and did not affect the anti-SP protective titer at the end of the study. Within 6 months following vaccination, the number of ARI episodes (p < 0.001) and the number of courses of antibacterial treatment (p < 0.0001) decreased twice. The median duration of ARI episodes decreased four times (p < 0.0001). Mild AEs (injection site reactions and short-term fever episodes) were found in 58 (15.6%) patients with JIA, and 1 patient (0.2%) developed an SAE. Conclusions: Simultaneous vaccination against pneumococcal and Hib infections reduces the frequency and duration of episodes of ARI, as well as the number of courses of antibacterial drugs, and does not lead to significant JIA flares. The number of reported AEs is consistent with what was expected. Full article

Background: Infections pose a significant risk of morbidity and mortality to patients on biologics, with the vaccination of both patients and their close contacts serving as a key preventive measure. Despite its importance, there are limited data on the vaccination coverage for this group, and no studies have examined the vaccination status of patients’ close contacts. Objectives: To assess vaccination rates among patients on biologics and their household contacts, identifying reasons for inadequate vaccination and examining factors influencing vaccination status and attitudes is crucial. Methods: A cross-sectional study was conducted from September 2022 to February 2023 at the two hospitals in Heraklion, Crete, including adult and pediatric patients on biologics. Data were collected through medical records and interviews and analyzed using Microsoft Excel 2016 and MedCalc2006. Results: Among the 446 adults, vaccination rates were as follows: 83% for COVID-19, 73.8% for influenza, 64.5% for the pneumococcal conjugate vaccine, 29.6% for the pneumococcal polysaccharide vaccine, and 4% for Tdap. Among the 26 children included, those with basic immunization schedule coverage exceeded 96%, but rates for the vaccines usually administered at adolescence were lower (Tdap: 47.8%, HPV: 42.1%, MenACWY: 66.7%). COVID-19 vaccination was at 38.5%. Regarding the additional vaccines recommended due to treatment-induced immunosuppression, 69.2% of pediatric patients received the annual influenza vaccine, while only 19.2% received the pneumococcal polysaccharide vaccine. Household contacts demonstrated low vaccination rates (<59%), except for COVID-19 (81%). Female gender (p < 0.007) and older age (by 1 year, p < 0.001) were associated with favorable attitudes and higher coverage in adults, while in pediatric patients, no statistically significant associations were found. A lack of physician recommendation was the primary reported reason for not being vaccinated. Conclusions: Significant vaccination gaps exist among patients on biologics and their close contacts, largely due to inadequate physician recommendations. Raising awareness and strengthening healthcare provider roles are essential to improve coverage in this high-risk group. Full article

Objectives: This study aimed to evaluate the immunogenicity and safety of a 13-valent pneumococcal polysaccharide conjugate vaccine (CRM197/TT) (PCV13i) in infants. Methods: A total of 1200 infants were randomly assigned to either the experimental PCV13i group or the control PCV13 group in a 1:1 ratio. Each group received a three-dose series of the vaccine at 2, 4, and 6 months of age, followed by a booster dose at 12–15 months. Blood samples were collected before and 30 days after both primary and booster vaccinations. The primary immunogenicity endpoints were the seropositive rate and the geometric mean concentration (GMC) of IgG antibodies against the 13 pneumococcal serotypes. The primary safety endpoint was the incidence of adverse reactions within 0–7 days and 0–30 days after vaccination. Results: Results showed that the experimental PCV13i was well tolerated, with a safety profile comparable to that of the control vaccine. Following primary vaccination, the GMCs of IgG responses against serotypes 1, 5, 6A, 6B, 14, and 18C in the experimental group were lower than those in the control group, while responses against serotypes 3, 4, 7F, 9V, 19A, 19F, and 23F were higher. The experimental group exhibited higher opsonophagocytic killing assay (OPA) geometric mean titers (GMTs) for serotypes 3, 7F, 19A, and 19F compared to the control group, while GMTs for serotypes 1, 5, 6A, and 18C were lower. Following booster vaccination, OPA GMTs of the experimental group remained higher than those of the control group for serotypes 3, 7F, and 19F, while GMTs for serotype 5 were lower. Both vaccines induced robust immune responses, with high seropositive rates and significant increases in antibody levels following vaccination. Conclusions: The experimental PCV13i demonstrated non-inferiority to the control PCV13 in terms of immunogenicity. Full article

Objectives: Pneumococcal disease (PD), caused by S. pneumoniae, is a serious global health issue, primarily for adults over 65, due to its high mortality and morbidity rates. Recently, broader-serotype vaccines have been introduced to cope with tremendous hospital costs and decreasing quality of life. Our study aims to systematically review the cost-effectiveness of current PCVs (pneumococcal conjugate vaccines) and PPVs (pneumococcal polysaccharide vaccine) from 2018 to April 2024. Methods: Articles were identified through PubMed, Embase, and Cochrane. Key outcomes include an improved incremental cost-effectiveness ratio (ICER) and quality-adjusted life-years (QALY), with the article’s quality assessed via the Consolidated Health Economic Evaluation Reporting Standards 2022 (CHEERS 2022). In total, 23 studies were included, with 22 studies of high quality and 1 of moderate quality. Results: These articles showed that PCV20 was the most cost-effective option compared with other vaccines, including PPV23, PCV13, PCV15, and PCV15/PPV23, for both young and older adults, regardless of risk factors. PCV20, when used alone, saved greater costs than PCV20, followed by PPV23. Conclusions: For countries applying lower-valency vaccines, switching to PCV20 as a single regimen would be the most beneficial for averting pneumococcal cases and reducing costs in adults aged 18–64 and over 65. Full article

Background: Vaccination against Streptococcus pneumoniae is advised for transplant recipients to reduce morbidity and mortality associated with invasive pneumococcal disease. However, data on alloantibodies after sequential vaccination (with a pneumococcal conjugate vaccine followed by a polysaccharide vaccine) are still lacking. Methods: In the current study, we determined HLA class I and II and major histocompatibility class I-related chain A (MICA) antibodies in 41 clinically stable kidney transplant recipients. These antibodies were measured prior to and post sequential pneumococcal vaccination over a period of 12 months. Alloantibodies were measured by Luminex bead-based assays, and pneumococcal IgG antibodies were measured by ELISA. Results: Over a 12-month period, the sequential analysis revealed no significant change in alloantibodies. One patient developed de novo donor-specific antibodies (DSA) 1.5 months after the first vaccination, with mean fluorescence intensities of up to 2300. These DSA became undetectable in the follow-up, and the patient showed no signs of allograft rejection. Another patient experienced a biopsy-proven borderline rejection 7 months after the first vaccination but did not develop de novo DSA. Both maintained stable kidney function. As expected, the pneumococcal antibodies increased significantly after vaccination (p < 0.0001). Conclusions: Given the overall risk of alloimmune responses in transplant recipients, we would not attribute the two noticeable patient courses to vaccination. Thus, we consider sequential vaccination immunologically safe. Full article

On-time receipt of pneumococcal vaccines is essential in patients with rheumatoid arthritis (RA) as immunosuppressive medications increase their risk of invasive pneumococcal disease (IPD). However, data regarding the impact of timely administration of these vaccines on the risk of developing IPD are lacking for RA patients. We conducted a retrospective cohort study to assess the impact of on-time vaccination for pneumococcal conjugate vaccine (PCV) 13 and pneumococcal polysaccharide vaccine (PPSV) 23 in patients treated for RA on the development of IPD using national Veterans Affairs data from 2010 to 2018. Patients > 18 years of age, diagnosed with RA, and newly initiated on RA treatment were included. Pneumococcal vaccine compliance was assessed by measuring on-time receipt of PCV13 and PPSV23 vaccinations. A total of 33,545 patients were included in the cohort. Non-compliance with PCV recommendations was associated with an increased risk of IPD in a multivariable logistic regression model. This finding was consistent whether IPD status was ascertained by International Classification of Diseases coding (OR 2.42, 95%CI 2.14–2.73) or microbiologic data (OR 1.64, 95%CI 1.26–2.14). Providers should actively seek opportunities to provide pneumococcal vaccinations to patients with RA, as their on-time administration is associated with a decreased risk of IPD. Full article

Multivalent pneumococcal vaccines have been developed successfully to combat invasive pneumococcal diseases (IPD) and reduce the associated healthcare burden. These vaccines employ pneumococcal capsular polysaccharides (PnPs), either conjugated or unconjugated, as antigens to provide serotype-specific protection. Pneumococcal capsular polysaccharides used for vaccine often contain residual levels of cell wall polysaccharides (C-Ps), which can generate a non-serotype specific immune response and complicate the desired serotype-specific immunity. Therefore, the C-P level in a pneumococcal vaccine needs to be controlled in the vaccine process and the anti C-P responses need to be dialed out in clinical assays. Currently, two types of cell-wall polysaccharide structures have been identified: a mono-phosphocholine substituted cell-wall polysaccharide C-Ps1 and a di-phosphocholine substituted C-Ps2 structure. In our effort to develop a next-generation novel pneumococcal conjugate vaccine (PCV), we have generated a monoclonal antibody (mAb) specific to cell-wall polysaccharide C-Ps2 structure. An antibody-enhanced HPLC assay (AE-HPLC) has been established for serotype-specific quantification of pneumococcal polysaccharides in our lab. With the new anti C-Ps2 mAb, we herein extend the AE-HPLC assay to the quantification and identification of C-Ps2 species in pneumococcal polysaccharides used for vaccines. Full article

Previously, it was shown that intranasally (i.n.) administered Corynebacterium pseudodiphtheriticum 090104 (Cp) or CP-derived bacterium-like particles (BLPs) improve the immunogenicity of the pneumococcal conjugate vaccine (PCV). This work aimed to deepen the characterization of the adjuvant properties of Cp and CP-derived BLPs for their use in the development of pneumococcal vaccines. The ability of Cp and CP-derived BLPs to improve both the humoral and cellular specific immune responses induced by i.n. administered polysaccharide-based commercial pneumococcal vaccine (Pneumovax 23^®) and the chimeric recombinant PSPF (PsaA-Spr1875-PspA-FliC) protein was evaluated, as well as the protection against Streptococcus pneumoniae infection in infant mice. Additionally, whether the immunization protocols, including Cp and CP-derived BLPs, together with the pneumococcal vaccines can enhance the resistance to secondary pneumococcal pneumonia induced after inflammatory lung damage mediated by the activation of Toll-like receptor 3 (TLR3) was assessed. The results showed that both Cp and CP-derived BLPs increased the immunogenicity and protection induced by two pneumococcal vaccines administered through the nasal route. Of note, the nasal priming with the PSPF T-dependent antigen co-administered with Cp or CP-derived BLPs efficiently stimulated humoral and cellular immunity and increased the resistance to primary and secondary pneumococcal infections. The CP-derived BLPs presented a stronger effect than live bacteria. Given safety concerns associated with live bacterium administration, especially in high-risk populations, such as infants, the elderly, and immunocompromised patients, BLPs emerge as an attractive mucosal adjuvant to improve the host response to pneumococcal infections and to enhance the vaccines already in the market or in development. Full article

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. Full article