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Keywords = anti-pneumococcal vaccination

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14 pages, 651 KiB  
Article
Safety and Efficacy of Simultaneous Vaccination with Polysaccharide Conjugate Vaccines Against Pneumococcal (13-Valent Vaccine) and Haemophilus Type B Infections in Children with Systemic Juvenile Idiopathic Arthritis: Prospective Cohort Study
by Ekaterina Alexeeva, Tatyana Dvoryakovskaya, Dmitry Kudlay, Anna Fetisova, Ivan Kriulin, Elizaveta Krekhova, Anna Kabanova, Vladimir Labinov, Elizaveta Labinova and Mikhail Kostik
Vaccines 2025, 13(6), 644; https://doi.org/10.3390/vaccines13060644 - 15 Jun 2025
Viewed by 635
Abstract
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 [...] Read more.
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
(This article belongs to the Special Issue Pneumococcal Vaccines: Current Status and Future Prospects)
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14 pages, 1461 KiB  
Case Report
Fatal Influenza B–MRSA Coinfection in a Healthy Adolescent: Necrotizing Pneumonia, Cytokine Storm, and Multi-Organ Failure
by Irina Profir, Cristina-Mihaela Popescu and Aurel Nechita
Children 2025, 12(6), 766; https://doi.org/10.3390/children12060766 - 13 Jun 2025
Viewed by 948
Abstract
Background: Influenza B usually causes mild illness in children. Severe and fatal cases can occur when complicated by secondary Staphylococcus aureus (S. aureus) pneumonia, including community-acquired methicillin-resistant Staphylococcus aureus (MRSA). We present a rare, rapidly progressive fatal case in an adolescent with [...] Read more.
Background: Influenza B usually causes mild illness in children. Severe and fatal cases can occur when complicated by secondary Staphylococcus aureus (S. aureus) pneumonia, including community-acquired methicillin-resistant Staphylococcus aureus (MRSA). We present a rare, rapidly progressive fatal case in an adolescent with no known medical history to highlight diagnostic and therapeutic pitfalls. Case Presentation: A 16-year-old boy with no known underlying conditions (unvaccinated for influenza) presented critically ill at “Sf. Ioan” Clinical Emergency Pediatric Hospital in Galați after one week of high fever and cough. He was in respiratory failure with septic shock, requiring immediate intubation and vasopressors. Chest X-ray (CXR) showed diffuse bilateral infiltrates (acute respiratory distress syndrome, ARDS). Initial laboratory tests revealed leukopenia, severe thrombocytopenia, disseminated intravascular coagulation (DIC), rhabdomyolysis, and acute kidney injury (AKI). Reverse transcription polymerase chain reaction (RT-PCR) confirmed influenza B, and blood cultures grew MRSA. Despite maximal intensive care, including mechanical ventilation, antibiotics (escalated for MRSA), antiviral therapy, and cytokine hemoadsorption therapy, the patient developed refractory multi-organ failure and died on hospital day 6. Autopsy revealed bilateral necrotizing pneumonia (NP) without radiographic cavitation, underscoring the diagnostic challenge. Discussion: The initial chest radiography showed diffuse bilateral pulmonary infiltrates, predominantly in the lower zones, with an ill-defined, patchy, and confluent appearance. Such appearance, in our case, was more suggestive of rapid progressive NP caused by MRSA rather than the typical pneumococcal one. This is one of the few reported cases of influenza B–MRSA coinfection with fulminant rhabdomyolysis and autopsy-confirmed necrosis. Our fulminant case illustrates the synergistic virulence of influenza and MRSA. Toxin-producing MRSA strains can cause NP and a “cytokine storm,” causing capillary leak, ARDS, shock, and DIC. Once multi-organ failure ensues, the prognosis is grim despite aggressive care. The absence of early radiographic necrosis and delayed anti-MRSA therapy (initiated after culture results) likely contributed to the poor outcome. Conclusions: Influenza B–MRSA co-infection, though rare, demands urgent empiric anti-MRSA therapy in severe influenza cases with leukopenia or shock, even without radiographic necrosis. This fatal outcome underscores the dual imperative of influenza vaccination and early, aggressive dual-pathogen targeting in high-risk presentations. Full article
(This article belongs to the Section Pediatric Infectious Diseases)
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53 pages, 2550 KiB  
Review
Structure, Function, and Regulation of LytA: The N-Acetylmuramoyl-l-alanine Amidase Driving the “Suicidal Tendencies” of Streptococcus pneumoniae—A Review
by Ernesto García
Microorganisms 2025, 13(4), 827; https://doi.org/10.3390/microorganisms13040827 - 5 Apr 2025
Cited by 1 | Viewed by 1487
Abstract
Streptococcus pneumoniae (pneumococcus) is a significant human pathogen responsible for a range of diseases from mild infections to invasive pneumococcal diseases, particularly affecting children, the elderly, and immunocompromised individuals. Despite pneumococcal conjugate vaccines having reduced disease incidence, challenges persist due to serotype diversity, [...] Read more.
Streptococcus pneumoniae (pneumococcus) is a significant human pathogen responsible for a range of diseases from mild infections to invasive pneumococcal diseases, particularly affecting children, the elderly, and immunocompromised individuals. Despite pneumococcal conjugate vaccines having reduced disease incidence, challenges persist due to serotype diversity, vaccine coverage gaps, and antibiotic resistance. This review highlights the role of LytA, a key autolysin (N-acetylmuramoyl-l-alanine amidase), in pneumococcal biology. LytA regulates autolysis, contributes to inflammation, and biofilm formation, and impairs bacterial clearance. It also modulates complement activation, aiding immune evasion. LytA expression is influenced by environmental signals and genetic regulation and is tied to competence for genetic transformation, which is an important virulence trait, particularly in meningitis. With the increase in antibiotic resistance, LytA has emerged as a potential therapeutic target. Current research explores its use in bacteriolytic therapies, vaccine development, and synergistic antibiotic strategies. Various compounds, including synthetic peptides, plant extracts, and small molecules, have been investigated for their ability to trigger LytA-mediated bacterial lysis. Future directions include the development of novel anti-pneumococcal interventions leveraging LytA’s properties while overcoming vaccine efficacy and resistance-related challenges. Human challenge models and animal studies continue to deepen our understanding of pneumococcal pathogenesis and potential treatment strategies. Full article
(This article belongs to the Section Antimicrobial Agents and Resistance)
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15 pages, 977 KiB  
Article
The Efficacy and Safety of Simultaneous Vaccination with Polysaccharide Conjugate Vaccines Against Pneumococcal (13-Valent Vaccine) and Haemophilus influenzae Type b Infections in Children with Juvenile Idiopathic Arthritis Without Systemic Manifestations: A Prospective Cohort Study
by Ekaterina Alexeeva, Tatyana Dvoryakovskaya, Anna Fetisova, Ivan Kriulin, Elizaveta Krekhova, Anna Kabanova, Vladimir Labinov, Elizaveta Labinova and Mikhail Kostik
Vaccines 2025, 13(2), 177; https://doi.org/10.3390/vaccines13020177 - 12 Feb 2025
Cited by 1 | Viewed by 1194
Abstract
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 [...] Read more.
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
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17 pages, 2084 KiB  
Article
Newborn Screening for Sickle Cell Disease in Catalonia between 2015 and 2022—Epidemiology and Impact on Clinical Events
by José Manuel González de Aledo-Castillo, Ana Argudo-Ramírez, David Beneitez-Pastor, Anna Collado-Gimbert, Francisco Almazán Castro, Sílvia Roig-Bosch, Anna Andrés-Masó, Anna Ruiz-Llobet, Georgina Pedrals-Portabella, David Medina-Santamaria, Gemma Nadal-Rey, Marina Espigares-Salvia, Maria Teresa Coll-Sibina, Marcelina Algar-Serrano, Montserrat Torrent-Español, Pilar Leoz-Allegretti, Anabel Rodríguez-Pebé, Marta García-Bernal, Elisabet Solà-Segura, Amparo García-Gallego, Blanca Prats-Viedma, Rosa María López-Galera, Abraham J. Paredes-Fuentes, Sonia Pajares García, Giovanna Delgado-López, Adoración Blanco-Álvarez, Bárbara Tazón-Vega, Cristina Díaz de Heredia, María del Mar Mañú-Pereira, José Luis Marín-Soria, Judit García-Villoria, Pablo Velasco-Puyó and on behalf of the Sickle Cell Disease Newborn Screening Group of Cataloniaadd Show full author list remove Hide full author list
Int. J. Neonatal Screen. 2024, 10(4), 69; https://doi.org/10.3390/ijns10040069 - 3 Oct 2024
Cited by 2 | Viewed by 2735
Abstract
In 2015, Catalonia introduced sickle cell disease (SCD) screening in its newborn screening (NBS) program along with standard-of-care treatments like penicillin, hydroxyurea, and anti-pneumococcal vaccination. Few studies have assessed the clinical impact of introducing NBS programs on SCD patients. We analyzed the incidence [...] Read more.
In 2015, Catalonia introduced sickle cell disease (SCD) screening in its newborn screening (NBS) program along with standard-of-care treatments like penicillin, hydroxyurea, and anti-pneumococcal vaccination. Few studies have assessed the clinical impact of introducing NBS programs on SCD patients. We analyzed the incidence of SCD and related hemoglobinopathies in Catalonia and the change in clinical events occurring after introducing NBS. Screening 506,996 newborns from 2015 to 2022, we conducted a retrospective multicenter study including 100 screened (SG) and 95 unscreened (UG) SCD patients and analyzed SCD-related clinical events over the first six years of life. We diagnosed 160 cases of SCD, with an incidence of 1 in 3169 newborns. The SG had a significantly lower median age at diagnosis (0.1 y vs. 1.68 y, p < 0.0001), and initiated penicillin prophylaxis (0.12 y vs. 1.86 y, p < 0.0001) and hydroxyurea treatment earlier (1.42 y vs. 4.5 y, p < 0.0001). The SG experienced fewer median SCD-related clinical events (vaso-occlusive crisis, acute chest syndrome, infections of probable bacterial origin, acute anemia requiring transfusion, acute splenic sequestration, and pathological transcranial Doppler echography) per year of follow-up (0.19 vs. 0.77, p < 0.0001), a reduced number of annual emergency department visits (0.37 vs. 0.76, p < 0.0001), and fewer hospitalizations (0.33 vs. 0.72, p < 0.0001). SCD screening in Catalonia’s NBS program has effectively reduced morbidity and improved affected children’s quality of life. Full article
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10 pages, 572 KiB  
Article
Epidemiology and Impact of Anti-Pneumococcal Vaccination and COVID-19 on Resistance of Streptococcus pneumoniae Causing Invasive Disease in Piedmont, Italy
by Alessandro Bondi, Emanuele Koumantakis, Antonio Curtoni, Anna Maria Barbui, Marco Peradotto, Daniela Lombardi, Roberto Casale, Silvia Alizzi, Elisa Zanotto, Lorena Charrier, Rossana Cavallo and Cristina Costa
Antibiotics 2024, 13(8), 740; https://doi.org/10.3390/antibiotics13080740 - 6 Aug 2024
Cited by 2 | Viewed by 1545
Abstract
Background: The international surveillance of antimicrobial resistance (AMR) reports S. pneumoniae as one of leading causes of death associated with AMR. Against invasive disease, several vaccinations are available and a reduction in AMR in S. pneumoniae has been observed. Here, we evaluated the [...] Read more.
Background: The international surveillance of antimicrobial resistance (AMR) reports S. pneumoniae as one of leading causes of death associated with AMR. Against invasive disease, several vaccinations are available and a reduction in AMR in S. pneumoniae has been observed. Here, we evaluated the impact of anti-pneumococcal vaccination policy and the SARS-CoV2 outbreak on AMR in S. pneumoniae causing invasive disease. Methods: We collected all strains of S. pneumoniae causing invasive disease from 2008 in the Piedmont region (Italy). Each strain was typed in order to identify the serogroup and data about AMR were collected. The population under surveillance was classified as infants, children, adults, and the old population. Results: We collected n = 2076 S. pneumoniae strains, with 21.9% and 40.3% being resistant to penicillin G and erythromycin, respectively. We reported an increased risk of infection with penicillin-resistant S. pneumoniae among all populations and evaluated whether the infection was caused by a serotype included in the vaccine formulation. A similar increase was observed after the SARS-CoV2 outbreak. Conclusions: In the Piedmont region, subsequently to the introduction of anti-pneumococcal vaccination, a significant increase in the risk of penicillin G-resistant invasive pneumococcal disease among infants and old population was reported. No significant impact was found for the SARS-CoV2 outbreak. Full article
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14 pages, 504 KiB  
Article
Preliminary Evaluation of the Safety and Immunogenicity of a Novel Protein-Based Pneumococcal Vaccine in Healthy Adults Aged 18–49: A Phase Ia Randomized, Double Blind, Placebo-Controlled Clinical Study
by Yanxia Wang, Gang Shi, Xue Wang, Zhiqiang Xie, Jinbo Gou, Lili Huang, Haitao Huang, Wangyang You, Ruijie Wang, Yongli Yang, Feiyu Wang, Tao Zhu and Dongyang Zhao
Vaccines 2024, 12(8), 827; https://doi.org/10.3390/vaccines12080827 - 23 Jul 2024
Cited by 6 | Viewed by 2072
Abstract
Background: Protein-based pneumococcal vaccines (PBPVs) may offer expanded protection against Streptococcus pneumoniae and tackle the antimicrobial resistance crisis in pneumococcal infections. This study examined the safety and immunogenicity in healthy adults vaccinated with three doses of a protein-based pneumococcal vaccine containing pneumococcal [...] Read more.
Background: Protein-based pneumococcal vaccines (PBPVs) may offer expanded protection against Streptococcus pneumoniae and tackle the antimicrobial resistance crisis in pneumococcal infections. This study examined the safety and immunogenicity in healthy adults vaccinated with three doses of a protein-based pneumococcal vaccine containing pneumococcal surface protein A (PspA) (PRX1, P3296 and P5668) and in combination with a recombinant detoxified pneumolysin protein (PlyLD). Methods: This phase Ia randomized, double blind, placebo-controlled clinical study enrolled healthy adults aged 18–49 years. The participants were randomized into experimental (low-dose, medium-dose, high-dose) and placebo groups in a ratio of 3:1. Three doses of investigational vaccine were given to the participants with an interval of two months. Safety endpoints included the occurrence of total adverse reactions, solicited local and systemic adverse reactions, unsolicited adverse reactions, serious adverse events (SAEs), and several laboratory parameters. Immunogenicity endpoints included geometric mean titers (GMT) of anti-PspA (PRX1, P3296 and P5668) and anti-PlyLD antibodies level as determined by ELISA, seropositivity rates of PspA and PlyLD antibodies (>4-fold increase) and neutralization activity of anti-Ply antibody in serum. Results: A total of 118 participants completed the study of three doses. The candidate PBPV was safe and well-tolerated in all experimental groups. No vaccine-related SAEs were observed in this study. Most solicited adverse reactions were mild and transient. The most frequently reported solicited adverse reactions in the medium- and high-dose groups was pain at the injection site, while in the low-dose group it was elevated blood pressure. The immunogenicity data showed a sharp increase in the GMT level of anti-PspA-RX1, anti-PspA-3296, anti-PspA-5668, and anti-PlyLD antibodies in serum. The results also showed that the elicited antibodies were dosage-dependent. The high-dose group showed a higher immune response against PspA-RX1, PspA-3296, PspA-5668, and PlyLD antigens. However, repeat vaccination did not increase the level of anti-PspA antibodies but the level of anti-PlyLD antibody. High seropositivity rates were also observed for anti-PspA-RX1, anti-PspA-3296, anti-PspA-5668, and anti-PlyLD antibodies. In addition, a significant difference in the GMT levels of anti-Ply antibody between the high-, medium-, and low-dose groups post each vaccination were indicated by neutralization activity tests. Conclusions: The PBPV showed a safe and immunogenic profile in this clinical trial. Taking into consideration both safety and immunogenicity data, we propose a single dose of 50 µg (medium dose) of PBPV as the optimum approach in providing expanded protection against Streptococcus pneumoniae. Full article
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14 pages, 332 KiB  
Article
Vaccination Open Day: A Cross-Sectional Study on the 2023 Experience in Lombardy Region, Italy
by Pier Mario Perrone, Simona Scarioni, Elisa Astorri, Chiara Marrocu, Navpreet Tiwana, Matteo Letzgus, Catia Borriello and Silvana Castaldi
Int. J. Environ. Res. Public Health 2024, 21(6), 685; https://doi.org/10.3390/ijerph21060685 - 27 May 2024
Cited by 2 | Viewed by 1834
Abstract
Background: Vaccination is a highly effective tool for controlling infectious diseases, particularly in populations at high risk of contagion due to clinical conditions or occupational exposure, such as healthcare workers. The purpose of this study is to present the open day event that [...] Read more.
Background: Vaccination is a highly effective tool for controlling infectious diseases, particularly in populations at high risk of contagion due to clinical conditions or occupational exposure, such as healthcare workers. The purpose of this study is to present the open day event that marked the beginning of the influenza and anti-COVID-19 vaccination campaign in the Lombardy region and to describe the experience of an Istituto di Ricovero e Cura a Carattere Scientifico in Milan. Methods: During the vaccination open day, eligible individuals received free vaccinations for influenza, COVID-19, pneumococcal disease, and shingles, as provided by the Lombardy Agenzia per la Tutela della Salute. In celebration of the centenary of the Università degli Studi di Milano, the Fondazione Ca’Granda Ospedale Policlinico, a contracted hospital of the university, created a special electronic diary for a total of 150 individuals, equally divided between children aged 2–6, pregnant women, and university staff. Results: At the regional level, a total of 6634 influenza vaccines, 2055 anti-COVID-19 vaccines, 108 anti-pneumococcal vaccines, and 37 anti-zoster vaccines were administered. A total of 3134 (47.3%) influenza vaccines, 1151 (56%) anti-COVID-19 vaccines, and 77 (62%) anti-pneumococcal vaccines, were given to individuals aged 60–79. No differences were observed between the total number of male and female vaccinees (1017 and 1038, respectively), who received the anti-COVID-19 vaccine. At the Policlinico Foundation, out of 150 available booking slots, 154 vaccines were administered, including 117 influenza vaccines. Conclusions: The establishment of vaccine open days is a beneficial way to increase vaccine compliance. Co-administration of little-known vaccinations outside of healthcare settings could also be a useful tool. Full article
12 pages, 1280 KiB  
Article
Identification and Quantification of a Pneumococcal Cell Wall Polysaccharide by Antibody-Enhanced Chromatography Assay
by James Z. Deng, Zhifeng Chen, James Small, Yue Yuan, Kara Cox, Aimin Tang, Jeanette Roman, Liming Guan, Katrina Feller, Frances Ansbro and Kalpit Vora
Vaccines 2024, 12(5), 469; https://doi.org/10.3390/vaccines12050469 - 28 Apr 2024
Cited by 3 | Viewed by 2279
Abstract
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 [...] Read more.
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
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22 pages, 2210 KiB  
Article
Enhancing Immune Response in Non-Small-Cell Lung Cancer Patients: Impact of the 13-Valent Pneumococcal Conjugate Vaccine
by Jolanta Smok-Kalwat, Paulina Mertowska, Izabela Korona-Głowniak, Sebastian Mertowski, Paulina Niedźwiedzka-Rystwej, Dominika Bębnowska, Krzysztof Gosik, Andrzej Stepulak, Stanisław Góźdź, Jacek Roliński, Zofia Górecka, Jan Siwiec and Ewelina Grywalska
J. Clin. Med. 2024, 13(5), 1520; https://doi.org/10.3390/jcm13051520 - 6 Mar 2024
Cited by 3 | Viewed by 1902
Abstract
Background: Non-small-cell lung cancer (NSCLC) is one of the most frequently diagnosed diseases among all types of lung cancer. Infectious diseases contribute to morbidity and mortality by delaying appropriate anti-cancer therapy in patients with NSCLC. Methods: The study aimed to evaluate the effectiveness [...] Read more.
Background: Non-small-cell lung cancer (NSCLC) is one of the most frequently diagnosed diseases among all types of lung cancer. Infectious diseases contribute to morbidity and mortality by delaying appropriate anti-cancer therapy in patients with NSCLC. Methods: The study aimed to evaluate the effectiveness of vaccination with the 13-valent pneumococcal conjugate vaccine (PCV13) in 288 newly diagnosed NSCLC patients. The analysis of the post-vaccination response was performed after vaccination by assessing the frequency of plasmablasts via flow cytometry and by assessing the concentration of specific anti-pneumococcal antibodies using enzyme-linked immunosorbent assays. Results: The results of the study showed that NSCLC patients responded to the vaccine with an increase in the frequencies of plasmablasts and antibodies but to a lesser extent than healthy controls. The immune system response to PCV13 vaccination was better in patients with lower-stage NSCLC. We found higher antibody levels after vaccination in NSCLC patients who survived 5 years of follow-up. Conclusions: We hope that our research will contribute to increasing patients′ and physicians′ awareness of the importance of including PCV13 vaccinations in the standard of oncological care, which will extend the survival time of patients and improve their quality of life. Full article
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11 pages, 2452 KiB  
Systematic Review
A Systematic Review and Meta-Analysis of Anti-Rheumatic Drugs and Pneumococcal Vaccine Immunogenicity in Inflammatory Arthritis
by Deepak Nagra, Katie Bechman, Maryam Adas, Zijing Yang, Edward Alveyn, Sujith Subesinghe, Andrew Rutherford, Victoria Allen, Samir Patel, Mark D. Russell, Andrew Cope, Sam Norton and James Galloway
Vaccines 2023, 11(11), 1680; https://doi.org/10.3390/vaccines11111680 - 2 Nov 2023
Cited by 5 | Viewed by 2309
Abstract
Background: Pneumococcal pneumonia is an important cause of morbidity and mortality amongst patients with inflammatory arthritis. Vaccination is recommended by the National Institute for Health and Care Excellence (NICE) but it remains unclear how vaccine efficacy is impacted by different immunosuppressive agents. Our [...] Read more.
Background: Pneumococcal pneumonia is an important cause of morbidity and mortality amongst patients with inflammatory arthritis. Vaccination is recommended by the National Institute for Health and Care Excellence (NICE) but it remains unclear how vaccine efficacy is impacted by different immunosuppressive agents. Our objective was to compare the chance of a seroconversion following vaccination against pneumococcus in patients with inflammatory arthritis to that in the general population, as well as to compare the chance of seroconversion across different targeted therapies. Methods: We searched MEDLINE, Embase and the Cochrane Library databases from inception until 20 June 2023. We included randomized controlled trials and observational studies. Aggregate data were used to undertake a pairwise meta-analysis. Our primary outcome of interest was vaccine seroconversion. We accepted the definition of serological response reported by the authors of each study. Results: Twenty studies were identified in the systematic review (2807 patients) with ten reporting sufficient data to be included in the meta-analysis (1443 patients). The chance of seroconversion in patients receiving targeted therapies, relative to the general population, was 0.61 (95% CI 0.35 to 1.08). The reduced odds of response were skewed strongly by the effects of abatacept and rituximab with no difference between patients on TNF inhibitors (TNFis) or IL-6 inhibition and healthy controls. Within different inflammatory arthritis populations the findings remained consistent, with rituximab having the strongest negative impact on vaccine response. TNF inhibition monotherapy was associated with a greater chance of vaccine response compared with methotrexate (2.25 (95% CI 1.28 to 3.96)). JAK inhibitor (JAKi) studies were few in number and did not present comparable vaccine response endpoints to include in the meta-analysis. The information available does not suggest any significant detrimental effects of JAKi on vaccine response. Conclusion: This updated meta-analysis confirms that, for most patients with inflammatory arthritis, pneumococcal vaccine can be administered with confidence and that it will achieve comparable seroconversion rates to the healthy population. Patients on rituximab were the group least likely to achieve a response and further research is needed to explore the value of multiple-course pneumococcal vaccination schedules in this population. Full article
(This article belongs to the Special Issue Vaccination of Patients with Immune-Mediated Diseases)
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20 pages, 368 KiB  
Review
The Global Burden of Community-Acquired Pneumonia in Adults, Encompassing Invasive Pneumococcal Disease and the Prevalence of Its Associated Cardiovascular Events, with a Focus on Pneumolysin and Macrolide Antibiotics in Pathogenesis and Therapy
by Ronald Anderson and Charles Feldman
Int. J. Mol. Sci. 2023, 24(13), 11038; https://doi.org/10.3390/ijms241311038 - 3 Jul 2023
Cited by 25 | Viewed by 9823
Abstract
Despite innovative advances in anti-infective therapies and vaccine development technologies, community-acquired pneumonia (CAP) remains the most persistent cause of infection-related mortality globally. Confronting the ongoing threat posed by Streptococcus pneumoniae (the pneumococcus), the most common bacterial cause of CAP, particularly to the non-immune [...] Read more.
Despite innovative advances in anti-infective therapies and vaccine development technologies, community-acquired pneumonia (CAP) remains the most persistent cause of infection-related mortality globally. Confronting the ongoing threat posed by Streptococcus pneumoniae (the pneumococcus), the most common bacterial cause of CAP, particularly to the non-immune elderly, remains challenging due to the propensity of the elderly to develop invasive pneumococcal disease (IPD), together with the predilection of the pathogen for the heart. The resultant development of often fatal cardiovascular events (CVEs), particularly during the first seven days of acute infection, is now recognized as a relatively common complication of IPD. The current review represents an update on the prevalence and types of CVEs associated with acute bacterial CAP, particularly IPD. In addition, it is focused on recent insights into the involvement of the pneumococcal pore-forming toxin, pneumolysin (Ply), in subverting host immune defenses, particularly the protective functions of the alveolar macrophage during early-stage disease. This, in turn, enables extra-pulmonary dissemination of the pathogen, leading to cardiac invasion, cardiotoxicity and myocardial dysfunction. The review concludes with an overview of the current status of macrolide antibiotics in the treatment of bacterial CAP in general, as well as severe pneumococcal CAP, including a consideration of the mechanisms by which these agents inhibit the production of Ply by macrolide-resistant strains of the pathogen. Full article
(This article belongs to the Special Issue Molecular Study of Bacterial Pneumonia and Pathogens)
14 pages, 2155 KiB  
Article
The Respiratory Commensal Bacterium Corynebacterium pseudodiphtheriticum as a Mucosal Adjuvant for Nasal Vaccines
by Ramiro Ortiz Moyano, Fernanda Raya Tonetti, Kohtaro Fukuyama, Mariano Elean, Mikado Tomokiyo, Yoshihito Suda, Vyacheslav Melnikov, Haruki Kitazawa and Julio Villena
Vaccines 2023, 11(3), 611; https://doi.org/10.3390/vaccines11030611 - 8 Mar 2023
Cited by 7 | Viewed by 3414
Abstract
Previously, we demonstrated that nasally administered Corynebacterium pseudodiphtheriticum 090104 (Cp) or its bacterium-like particles (BLPs) increase the resistance of mice against bacterial and viral respiratory pathogens by modulating the innate immunity. In this work, we evaluated the ability of Cp and BLPs to [...] Read more.
Previously, we demonstrated that nasally administered Corynebacterium pseudodiphtheriticum 090104 (Cp) or its bacterium-like particles (BLPs) increase the resistance of mice against bacterial and viral respiratory pathogens by modulating the innate immunity. In this work, we evaluated the ability of Cp and BLPs to stimulate alveolar macrophages, and to enhance the humoral immune response induced by a commercial vaccine against Streptococcus pneumoniae. In the first set of experiments, Cp or the BLPs were incubated with primary cultures of murine alveolar macrophages and the phagocytic activity, and the production of cytokines was evaluated. The results revealed that Cp and BLPs were efficiently phagocyted by respiratory macrophages and that both treatments triggered the production of TNF-α, IFN-γ, IL-6, and IL-1β. In the second set of experiments, 3-week-old Swiss mice were intranasally immunized at days 0, 14, and 28 with the pneumococcal vaccine Prevenar®13 (PCV), Cp + PCV, or BLPs + PCV. On day 33, samples of bronco-alveolar lavages (BAL) and serum were collected for the study of specific antibodies. In addition, immunized mice were challenged with S. pneumoniae serotypes 6B or 19F on day 33 and sacrificed on day 35 (day 2 post-infection) to evaluate the resistance to the infection. Both Cp + PCV and BLPs + PCV groups had higher specific serum IgG and BAL IgA antibodies than the PCV control mice. In addition, the mice that were immunized with Cp + PCV or BLPs + PCV had lower lung and blood pneumococcal cell counts as well as lower levels of BAL albumin and LDH, indicating a reduced lung damage compared to the control mice. Improved levels of anti-pneumococcal antibodies were also detected in the serum and BAL samples after the challenges with the pathogens. The results demonstrated that C. pseudodiphtheriticum 090104 and its bacterium-like particles are capable of stimulating the respiratory innate immune system serving as adjuvants to potentiate the adaptive humoral immune response. Our study is a step forward in the positioning of this respiratory commensal bacterium as a promising mucosal adjuvant for vaccine formulations aimed at combating respiratory infectious diseases. Full article
(This article belongs to the Special Issue Immunology and Protective Efficacy of Adjuvanted Vaccines)
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20 pages, 3209 KiB  
Review
Caveolae-Mediated Extracellular Vesicle (CMEV) Signaling of Polyvalent Polysaccharide Vaccination: A Host–Pathogen Interface Hypothesis
by Shengwen Calvin Li and Mustafa H. Kabeer
Pharmaceutics 2022, 14(12), 2653; https://doi.org/10.3390/pharmaceutics14122653 - 30 Nov 2022
Cited by 3 | Viewed by 2797
Abstract
We published a study showing that improvement in response to splenectomy associated defective, in regards to the antibody response to Pneumovax® 23 (23-valent polysaccharides, PPSV23), can be achieved by splenocyte reinfusion. This study triggered a debate on whether and how primary and [...] Read more.
We published a study showing that improvement in response to splenectomy associated defective, in regards to the antibody response to Pneumovax® 23 (23-valent polysaccharides, PPSV23), can be achieved by splenocyte reinfusion. This study triggered a debate on whether and how primary and secondary immune responses occur based on humoral antibody responses to the initial vaccination and revaccination. The anti-SARS-CoV-2 vaccine sheds new light on the interpretation of our previous data. Here, we offer an opinion on the administration of the polyvalent polysaccharide vaccine (PPSV23), which appears to be highly relevant to the primary vaccine against SARS-CoV-2 and its booster dose. Thus, we do not insist this is a secondary immune response but an antibody response, nonetheless, as measured through IgG titers after revaccination. However, we contend that we are not sure if these lower but present IgG levels against pneumococcal antigens are clinically protective or are equally common in all groups because of the phenomenon of “hyporesponsiveness” seen after repeated polysaccharide vaccine challenge. We review the literature and propose a new mechanism—caveolae memory extracellular vesicles (CMEVs)—by which polysaccharides mediate prolonged and sustained immune response post-vaccination. We further delineate and explain the data sets to suggest that the dual targets on both Cav-1 and SARS-CoV-2 spike proteins may block the viral entrance and neutralize viral load, which minimizes the immune reaction against viral attacks and inflammatory responses. Thus, while presenting our immunological opinion, we answer queries and responses made by readers to our original statements published in our previous work and propose a hypothesis for all vaccination strategies, i.e., caveolae-mediated extracellular vesicle-mediated vaccine memory. Full article
(This article belongs to the Section Drug Delivery and Controlled Release)
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9 pages, 370 KiB  
Article
Multidimensional Frailty and Vaccinations in Older People: A Cross-Sectional Study
by Nicola Veronese, Giusy Vassallo, Maria Armata, Laura Cilona, Salvatore Casalicchio, Roberta Masnata, Claudio Costantino, Francesco Vitale, Giovanni Maurizio Giammanco, Stefania Maggi, Shaun Sabico, Nasser M. Al-Daghri, Ligia J. Dominguez and Mario Barbagallo
Vaccines 2022, 10(4), 555; https://doi.org/10.3390/vaccines10040555 - 3 Apr 2022
Cited by 6 | Viewed by 2841
Abstract
It is known that influenza, herpes zoster, pneumococcal and pertussis infections may increase morbidity and mortality in older people. Vaccinations against these pathogens are effective in older adults. Frailty seems to be an important determinant of vaccination rates, yet data supporting this association [...] Read more.
It is known that influenza, herpes zoster, pneumococcal and pertussis infections may increase morbidity and mortality in older people. Vaccinations against these pathogens are effective in older adults. Frailty seems to be an important determinant of vaccination rates, yet data supporting this association are still missing. Therefore, we aimed to investigate the prevalence of four recommended vaccinations (influenza, herpes zoster, pneumococcal and diphtheria-tetanus-pertussis) and the association with multidimensional frailty assessed using a self-reported comprehensive geriatric assessment tool, i.e., the multidimensional prognostic index (SELFY-MPI). Older participants visiting the outpatient clinic of Azienda Ospedaliera Universitaria, Palermo, Italy were included. The SELFY-MPI questionnaire score was calculated based on eight different domains, while the vaccination status was determined using self-reported information. We included 319 participants from the 500 initially considered (63.8%). Vaccination against influenza was observed in 70.5% of the cases, whilst only 1.3% received the vaccination against diphtheria-tetanus-pertussis. Participants with higher SELFY-MPI scores were more likely to report vaccination against pneumococcus (45.6 vs. 28.3%, p = 0.01), whilst no significant differences were observed for the other vaccinations. In conclusion, the coverage of recommended vaccinations is low. Higher SELFY-MPI scores and vaccination status, particularly anti-pneumococcus, appear to be associated, but future studies are urgently needed for confirming that frailty is associated with vaccination status in older people. Full article
(This article belongs to the Special Issue Knowledge about Vaccines and Vaccination in Older People)
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