Search Results (608)

Background/Objectives: This study aimed to evaluate the immunogenicity and safety of a Meningococcal A and C Polysaccharide Conjugate Vaccine in 3–5-month-old infants. A single-center, randomized, blinded, positive-controlled phase III clinical trial was conducted in Binyang County, Guangxi Zhuang Autonomous Region, China. Infants aged 3–5 months were randomly assigned to the experimental or control group at a 1:1 ratio. Both groups received 3 primary doses with a 1-month interval between each dose, and a booster dose administered at 18 months of age. Seroconversion rate, seropositivity rate, and GMT of bactericidal antibodies against Neisseria meningitidis groups A and C were assessed, along with adverse reactions within the full course of primary immunization and 30 days after booster immunization. Results: After primary immunization, in the experimental group’s pre-vaccination antibody-negative infants, seroconversion rates for groups A and C exceeded 90%, with antibody fold increases over 90 times; its seroconversion rates and GMT were non-inferior to the control group. Before the 18-month booster, the experimental group’s group A and C antibody seropositivity rates dropped to approximately 70% and 30% (slightly higher than the control), respectively. After booster immunization, the antibody levels against groups A and C were significantly higher than those before the booster and the positive rates and GMT levels of the two groups were similar. Adverse reactions were mainly solicited systemic ones (fever most common), with no statistical difference between groups. Conclusions: The experimental vaccine shows great immunogenicity and safety in infants aged 3–5 months and is non-inferior to the control vaccine. In the booster immunization phase of the control group, sequential vaccination with vaccines from different manufacturers was adopted, and the immunogenicity was good. Full article

Background: COPD and stable angina are common in older adults, increasing the risk of respiratory and cardiovascular complications. Pneumococcal vaccination is recommended to reduce this burden. This study evaluated the 10-year impact of 13-valent pneumococcal conjugate vaccine (PCV13) on community-acquired pneumonia (COPD), COPD exacerbations, hospitalizations, and survival in this cohort. Methods: A total of 483 male patients with COPD and/or stable angina received a single dose of PCV13 and were divided into three groups: Group 1 (n = 140): vaccinated with COPD; Group 2 (n = 167): vaccinated with COPD and stable angina; and Group 3 (n = 176): unvaccinated with COPD. Primary endpoints were CAP cases, COPD exacerbations, and hospitalizations; the secondary endpoint was survival. Analysis used generalized linear models, Cox regression, and Kaplan–Meier survival curves. Results: PCV13 significantly reduced CAP in patients with COPD alone but not in those with comorbid angina. Although CAP, exacerbations, and hospitalizations increased over time, vaccinated groups consistently showed lower rates than the unvaccinated group. Survival was higher in both vaccinated groups over 10 years. Conclusions: PCV13 was associated with a reduced risk of CAP, COPD exacerbations, hospitalizations, and improved survival in older adults with COPD and stable angina. These findings support the vaccine’s potential to improve outcomes in multimorbid populations and its inclusion in clinical guidelines and adult immunization programs for high-risk older adults. Full article

Tuberculosis (TB), primarily caused by Mycobacterium tuberculosis (Mtb), remains a leading cause of infectious disease mortality worldwide. Global TB control efforts face several hurdles, including the lack of a broadly effective vaccine, limited sensitivity of current diagnostics, particularly for paucibacillary and extrapulmonary TB, and significant adverse effects associated with prolonged small-molecule drug regimens. The growing prevalence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains further underscores the urgent need for innovative therapeutic strategies. We outline characteristics of next-generation TB therapeutics. We show that antibody (Ab)-drug conjugates (ADCs) satisfy many of those desirable characteristics. Since a major hurdle to this approach lies in Mtb-specific Abs, we highlight an open-access resource comprising a broad panel of Mtb-specific mouse monoclonal antibodies targeting key factors involved in Mtb survival, immune evasion, and pathogenesis. These critical Mtb virulence factors include heat shock proteins (GroES, DnaK, and HspX), surface-associated or secreted proteins (LAM, Ag85, HBHA, Mpt64/CFP-21, and PhoS1/PstS1), cell wall/envelope-associated proteins (LprG/p27), and detoxifying enzymes (KatG and SodA). The resource provides full-length sequences of the immunoglobulin variable regions, enabling antibody engineering and facilitating translational TB research across vaccine design, diagnostic development, and immunotherapeutic applications, in addition to ADCs. This ADC targeted delivery strategy holds promise for overcoming TB heterogeneity and eliminating both active and dormant Mtb populations within a single therapeutic formulation and offers a novel avenue for precision TB treatment. Full article

Angiosarcomas are highly aggressive soft tissue tumors with poor prognosis in both humans and dogs. In dogs, visceral hemangiosarcoma offers a relevant spontaneous model for evaluating novel therapies. Surgery alone yields a median survival of 1–3 months, and treatment with doxorubicin (DOX), alone or in combination (e.g., with propranolol), modestly extends median survival time to 5–7 months, with a 1-year survival of around 10%. We developed a conjugate vaccine technology, called immune Boost (iBoost), and hypothesized that combining DOX with an iBoost vaccine targeting extracellular vimentin (eVim) could improve survival without added toxicity. Twenty-three dogs with visceral hemangiosarcoma received six cycles of DOX every two weeks post-splenectomy, alongside four doses every other week of eVim iBoost immunotherapy, followed by maintenance vaccinations every two months. Outcomes were compared to historical controls treated with DOX alone. Compared to the control group the median overall survival time increased from 136 to 235 days (NS), restricted mean survival time at one year increased with 81 days (p = 0.02) and 1-year survival rate was 44% versus 14% (p = 0.0344). The combination was well-tolerated, with no systemic vaccine-related toxicity. Adding dog eVim vaccine to DOX appears to improve survival without added toxicity in dogs with hemangiosarcoma. These results support further clinical development, including evaluation in human angiosarcoma. Full article

Streptococcus pneumoniae has been a PCV10 vaccine-preventable agent in Bulgaria since 2010. Our objective is to determine the phylogenetic structure of 170 invasive and non-invasive pneumococcal isolates, focusing on their serotypes and antimicrobial susceptibility. Serotyping was performed using latex agglutination, capsular swelling reaction, and serotype-specific PCRs. Antibiotic susceptibilities were assessed by broth microdilution. MLST was conducted to define the clonal composition. The non-PCV10 serotypes accounted for 88.2%. The predominant invasive pneumococcal disease (IPD) serotypes were 19A (39.3%), 19F (21.4%), 6C (10.7%), 7F (7.1%), and 3 (7.1%). The prevalent NIPD serotypes were 19A (18.3%), 6C (15.5%), 3 (10.6%), 15A (7.7%), and 6A (6.3%). The overall antimicrobial non-susceptibility rates were: benzylpenicillin (55.2%), ceftriaxone (15.2%), cefuroxime (35.8%), amoxicillin-clavulanic acid (38.8%), erythromycin (60.5%), clindamycin (57.0%), tetracycline (43.5%), trimethoprim-sulfamethoxazole (62.9%), and chloramphenicol (13.5%). The multidrug resistance (MDR) strains were 60.5%. The predominant clone CC320, represented 20.0% MDR 19A and 19F strains linked to Taiwan^19F-14 and GPSC1. CC273/Greece^6B-22 and CC386 accounted for 5.3% 6A and 6C isolates. Most serotype 3 isolates are associated with CC505, associated with Netherlands³-31 and GPSC12. Switching to a conjugate vaccine with broader serotype coverage could reduce the incidence of 19A, 6C, and 15A MDR S. pneumoniae clones in our country. Full article

Typhoid fever, measles, and rubella continue to contribute significantly to childhood morbidity and mortality in India. In line with WHO recommendations for co-administration of Typhoid Conjugate Vaccine (TCV) and measles–rubella (MR) vaccine at 9 months of age, this phase IV, randomized, open-label, multicenter clinical trial was conducted to assess their immunological compatibility and safety when administered concomitantly. A total of 900 healthy Indian infants aged 9–10 months were randomized into three groups: Group A received TCV and MR vaccine concomitantly; Group B received MR on Day 0 and TCV on Day 28; Group C received TCV on Day 0 and MR on Day 28. Subjects were followed for 6 months after concomitant/last vaccination. Seroconversion rates (SC) in Groups A/B/C at Day 28 were 90.2%/75.3%/89.5% for anti-Vi; 80.4%/75.2%/77.7% for anti-measles, and 87.7%/84.0%/85.2% for anti-rubella antibodies. By study end, SC for anti-Vi was 87.1%/71.6%/83.0%, while SC for anti-measles and anti-rubella reached ~90% and ≥98%, respectively, across all groups. Geometric mean titers increased significantly for all antigens, with no evidence of immunological interference. Safety assessments showed adverse events in 23.9%/32.0%/32.7% participants in Group A/B/C. Most adverse events were mild, and only one serious adverse event was reported. These findings support the co-administration of TCV and MR vaccine as a safe and effective strategy. Full article

Penile squamous cell carcinoma (PSCC) represents a malignancy with low incidence. Despite advances in chemotherapy-based management, outcomes for patients with locally advanced and metastatic disease remain poor, with 5-year survival rates of 51% and 9%, respectively. Early diagnosis is crucial, yet psychosocial/structural barriers often delay it. Treatment strategies are stage-dependent, ranging from organ-sparing surgery and targeted radiotherapy for early-stage disease to cisplatin-based chemotherapy for locally advanced and metastatic cases. However, systemic therapies provide modest survival benefits and can expose the patient to unnecessary toxicities. Immunotherapy has emerged as a promising area, given the high expression of PD-L1 in PSCC and the significant proportion of HPV-driven tumors. Although initial results from immunotherapy-based trials are limited, preliminary trials such as HERCULES, ALPACA, PULSE, and PERICLES aim to define their role better. Similarly, combination regimens utilizing toripalimab in combination with nimotuzumab and taxane-based chemotherapy (TNT) followed by consolidative surgery are currently underway. Furthermore, the development of therapeutic HPV vaccines offers a novel strategy to enhance local antitumor immunity. Antibody–drug conjugates (ADCs) targeting HER-2, Trop-2, and Nectin-4 antigens represent another evolving therapeutic avenue that has shown preliminary promising results. As the landscape of penile cancer treatment continues to grow, incorporating these novel strategies could further improve survival outcomes and/or offer improved quality of life. This review provides a comprehensive overview of emerging systemic therapies in PSCC, underscoring ongoing research efforts to address unmet needs. Full article

Background/Objectives: Group B Streptococcus (GBS) is a significant cause of perinatal infection in neonates and infants. Complications could include neonatal sepsis and meningitis, preterm birth, stillbirth, or death. Though no GBS vaccine is currently licensed, maternal immunization is expected to be a highly effective strategy to address invasive GBS disease—particularly in low- and middle-income countries (LMICs), where the disease burden is the greatest and access to existing interventions is limited. In this study, we present a novel hexavalent GBS vaccine candidate with a unique combination of serotypes (ST)—Ia, Ib, II, III, V, and VII—that could be an efficacious and cost-effective intervention, with the broadest coverage of 99% against circulating serotypes globally. Methods: The 6-valent conjugate vaccine candidate, GBS-06, is developed using a novel approach by linking the six polysaccharides (PS) to recombinant cross-reactive material 197 (rCRM197) carrier protein derivatized with a hydrazide-polyethylene glycol-hydrazide (HZ-PEG-HZ) linker. A repeat-dose GLP toxicology study with GBS-06 was conducted at the highest clinical dose of 20 µg in rabbits with saline as the placebo control. Results: The results reveal induction of robust anti-capsular polysaccharide-specific IgG responses against each of the six serotypes after each dose with the highest antibody GMCs at Day 49 following the third dose. Conclusions: Hence, this work is the first demonstration of strong immunogenicity achieved using a linker (HZ-PEG-HZ) for GBS glycoconjugate vaccine development. The positive data from the study have strong implications in the advancement of the candidate for evaluation in clinical trials and provide a licensure pathway for maternal immunization. Full article

Background: Trust in information sources is essential to enhance an individual’s understanding of the message and boost their willingness to change or act on specific health behavior, including vaccine uptake. This study explores the association between trust in information sources and parents’ knowledge, attitudes, and practices regarding their children’s 13-valent pneumococcal conjugate vaccine (PCV13) uptake across seven cities in the Yangtze River Delta (YRD) region in China. Methods: A cross-sectional web-based survey was conducted from May to June 2023. Adult parents (N = 1304) who had at least one child aged 24 months or less and lived in the YRD region were recruited. The Adjusted Ordinary Least Squares (OLSs) regression model was applied to estimate the association between participants’ level of trust in different information sources and their knowledge, attitudes, and practices of children’s PCV13 vaccination. Results: Information from the Disease Control and Prevention Center (CDC) source received the highest trust score. Age, gender, education, and annual household income were related to varied trust levels in specific sources. Trust in the health service provider source was significantly associated with a better command of PCV13 knowledge, acceptance of PCV13, and a higher likelihood of vaccination. Trust in online community sources was positively associated with vaccine uptake. Conclusions: The study participants highly trusted information from health service provider sources. These sources may be effective channels with potential to enhance parents’ vaccine knowledge and acceptance of PCV13. Public health workers could utilize trusted sources to disseminate the benefits of the PCV13 and encourage the uptake of the vaccine. Full article

Background/Objectives: Meningococcal disease (MD) remains a significant public health concern worldwide. In Serbia, mandatory immunization against MD with the meningococcal polysaccharide vaccine (MenAC) for high-risk groups and international travelers was introduced in 2006. Since 2017, the polysaccharide vaccine has been replaced with the quadrivalent meningococcal conjugate vaccine (MenACWY). The aim of this study was to analyze long-term trends in incidence, age-specific patterns, seasonality, and lethality of invasive meningococcal disease (IMD) in the Autonomous Province of Vojvodina (AP Vojvodina), Serbia, over a 28-year period. Methods: A descriptive study analyzed all reported cases of IMD in AP Vojvodina, from 1997 to 2024. Data were obtained from the regional communicable disease surveillance system, based on mandatory hospital reporting and case classification according to national and WHO guidelines. Temporal, demographic, and clinical characteristics, along with disease outcomes, were analyzed. Results: From 1997 to 2024, 175 IMD cases were reported in AP Vojvodina. The annual incidence peaked in 1997 (1.24/100,000), with smaller surges in 2003 and 2005. Since 2006, coinciding with the introduction of immunization against MD, a sustained decline has been observed, with incidence rarely exceeding 0.30/100,000. A slight resurgence occurred in 2023–2024, with 13 cases reported. From 1997 to 2024, IMD in AP Vojvodina exhibited a clear seasonal pattern, with most cases occurring in winter and early spring, peaking in January (17%), March (12%), and February (11%), and the fewest cases occuring in the summer months. Throughout the study period, the highest IMD incidence rates were consistently observed among infants <1 year of age and children aged 1–4 years, with peaks of up to 22.9/100,000 and 16.0/100,000, respectively. Incidence was much lower in older age groups, especially adults. After a 2006 peak, rates declined across all ages, with a slight resurgence in 2023–2024 among children and adolescents. Children aged 1–4 years made up the largest share of IMD cases, peaking in January–March (45.1%). Half of the infant cases were recorded in October–November, while cases in older children, adolescents, and adults were fewer and showed varied monthly patterns, with small peaks in winter and early spring. During the 28-year study period, the highest IMD mortality rate was observed among infants <1 year of age (0.59 per 100,000 population), followed by children aged 1–4 years (0.32 per 100,000). Mortality rates declined progressively with increasing age, with the lowest rate recorded among individuals aged ≥40 years (0.01 per 100,000). Of the 175 IMD cases reported in AP Vojvodina (1997–2024), 21 were fatal (case fatality rate [CFR] = 12.0%). The CFR of IMD varied across age groups. The highest CFR was observed among individuals aged ≥40 years (21.4%), followed by the 5–9 years (17.4%) and <1 year (16.7%) age groups. None of the patients had been vaccinated against MD. Fatal outcomes were more common in children aged 1–4 years and among rural residents, though differences were not statistically significant (p > 0.05). Most deaths (57.1%) occurred in the first quarter of the year. A strong association was found between clinical form and outcome, with meningococcal sepsis being significantly more frequently associated with fatality than meningitis (p = 0.0002). Deaths were sporadic over time, with most occurring within 1–2 days of notification. All confirmed fatal cases were due to serogroup B. Conclusions: MD remains a rare yet serious public health threat in AP Vojvodina. Mortality rates indicate that the public health impact of this disease is greatest among the youngest age groups; however, the risk of death, i.e., disease severity, does not appear to be age dependent. The recent rise in cases, high fatality among sepsis patients, and absence of prior vaccination among all IMD cases highlight the need for enhanced surveillance, physician education, and consideration of introducing both MenACWY and MenB vaccines for high-risk groups. Full article

Elite athletes are at an increased risk of infections due to behavioral and social factors and frequent travel. Furthermore, heavy physical exercise may induce immunosuppression. Most infections in athletes are acute respiratory illnesses (ARIs) with various viral etiologies. Although athletes, as young, healthy adults, are not at risk for severe infections, a prolonged ARI may ruin a training season or a significant competition or may spread within a sports team. Many common infections are vaccine-preventable. This Opinion advocates for more active vaccination among athletes, although some of the vaccines are not officially recommended for young adults. New respiratory syncytial virus (RSV) protein vaccines are effective and well-tolerated. Yearly influenza and COVID-19 vaccinations are strongly recommended. Conjugated polyvalent pneumococcal vaccines are recommended because they may also induce protection against respiratory viral infections. Pertussis and measles outbreaks are occurring globally. The history of measles vaccination should be reviewed, and consideration should be given to a pertussis booster vaccination (Tdap). A recombinant vaccine can effectively prevent herpes zoster. The vaccination of elite athletes is a cost-effective and powerful tool, but it is currently underused. The sports medicine community can address vaccine hesitancy among athletes by listening to their concerns and giving accurate information. Full article

Background/Objectives: Pneumococcal conjugate vaccines (PCVs) have significantly reduced invasive pneumococcal disease (IPD) globally. We conducted a systematic review to assess whether serotype and antimicrobial resistance trends in the Middle East and North Africa (MENA) reflect global patterns post-PCV introduction. Methods: We searched the CINAHL, MEDLINE, PUBMED, EMBASE, Global Health, Global Index Medicus, EBSCO, Scopus, and Cochrane databases for articles published from inception to 24 January 2024. Eligible studies were original articles in English or French, reporting IPD serotype distribution or antimicrobial susceptibility in the MENA region. Risk of bias was assessed using the STROBE checklist. Results: Eighty-nine studies from 18 countries were included. A decline in PCV7 serotypes was observed following the introduction of PCV10 or PCV13, which was more pronounced in PCV10-era studies. Serotype 3 increased post-PCV13 era, while 19A declined only after PCV10. An expansion in PCV20 serotypes and non-vaccine types (NVTs) was noted in PCV13-implementing countries. Antimicrobial resistance data were insufficient to provide a reliable trend. Limitations: There was limited AMR data and variable surveillance quality across countries. Conclusions: PCV introduction resulted in a modest decrease in PCV7 serotypes and a variable impact on PCV13 serotypes. This, along with the increase in PCV20 serotypes, indicates that higher-valency PCVs might provide better serotype coverage in the region. The study highlights the need for more robust surveillance across the region. Registration: CRD42018104529. Full article

Acute myeloid leukemia (AML) is an aggressive hematologic malignancy characterized by the clonal proliferation of myeloid precursors and rapid progression. Historically consisting of intensive chemotherapy, AML management has evolved significantly due to advances in molecular diagnostics and risk stratification. This review discusses current therapeutic paradigms in AML, emphasizing the growing role of personalized medicine across age and risk groups. For younger, fit patients, intensive regimens such as the “7 + 3” protocol remain the standard, often enhanced by targeted agents like FMS-like tyrosine kinase 3 (FLT3) and IDH inhibitors. Older or unfit individuals benefit from low-intensity treatments such as hypomethylating agents combined with venetoclax, now considered a frontline standard of care. The use of liposomal chemotherapy (CPX-351), measurable residual disease (MRD) monitoring, and maintenance therapy further refine post-remission strategies. Emerging therapies, including menin inhibitors, antibody–drug conjugates, and immunotherapies like CAR-T cells and vaccines, offer additional options, especially in relapsed/refractory settings. This comprehensive review outlines the current landscape and future directions in AML therapy, emphasizing the transition toward individualized, mutation-driven treatment strategies. Full article

Chronic pain affects millions of individuals globally and continues to pose a major burden on patients and healthcare systems. Traditional analgesics, such as opioids and nonsteroidal anti-inflammatory drugs, often provide only partial relief and are frequently associated with significant side effects and risks of misuse. In recent years, vaccines that target molecules involved in pain signaling have emerged as an innovative therapeutic strategy. These vaccines aim to induce long-lasting immune responses against key mediators of nociception, including nerve growth factor (NGF), calcitonin gene-related peptide (CGRP), substance P, and voltage-gated sodium channels such as Nav1.7. By promoting the production of specific antibodies, anti-pain vaccines have the potential to achieve analgesic effects with longer duration, reduced need for frequent administration, and improved accessibility. Multiple vaccine platforms are under investigation, including virus-like particles, peptide-protein conjugates, and nucleic acid technologies. Although preclinical studies have shown promising efficacy and safety profiles, clinical evidence is still limited to early-stage trials, particularly for migraine. This narrative review summarizes current knowledge on therapeutic vaccines for pain, discusses the immunological and technological advances in the field, and outlines future directions. Full article

Background/Objectives: Toxoplasma gondii is a major cause of zoonotic infections in both humans and animals, resulting in significant mortality in susceptible species, such as New World primates and marsupials. Toxoplasmosis is particularly concerning in zoos and wildlife reserves, where outbreaks threaten conservation efforts for endangered species. In the absence of a commercially available vaccine against toxoplasmosis for humans and captive wild animals, current prevention strategies are limited to restricting the access of cats to enclosures, controlling rodent populations, and maintaining strict food hygiene. Recent research has shown promising results with an intranasal vaccine (VXN-Toxo) composed of maltodextrin nanoparticles conjugated with a purified, inactivated T. gondii parasite. This experimental vaccine does not pose a risk of causing disease and offers advantages such as better stability compared with live pathogen-based vaccines. Methods: This study presents a large-scale evaluation of the effect of VXN-Toxo administered to captive wildlife across 20 zoos in Europe and the Americas between 2017 and 2025. Seven hundred and eighty-four animals, representing over 58 species (including primates, marsupials, rodents, and felids), were vaccinated without any adverse events reported. Results: Retrospective mortality data from 20 participating zoological institutions revealed an overall 96.7% reduction—and, in many cases, a complete elimination—of toxoplasmosis-associated deaths post vaccination. Conclusions: These results demonstrate, for the first time, consistent and broad-spectrum protection against T. gondii of different strains in a wide array of captive wildlife species. This universal vaccine represents a promising tool for toxoplasmosis prevention in zoological collections, with significant implications for animal health and conservation strategies. Full article