Search Results (25,026)

Background: Cervical cancer poses a threat to the health of women globally. Adolescent girls are the primary target population for HPV vaccination, and guardians’ attitude towards the HPV vaccine plays a significant role in determining the vaccination status among adolescent girls. Objectives: This study aimed to explore the factors influencing guardians’ HPV vaccine acceptance for their girls and provide clues for the development of health intervention strategies. Methods: Combining the health belief model as a theoretical framework, a questionnaire-based survey was conducted. A total of 2157 adolescent girls and their guardians were recruited. The multivariable logistic model was applied to explore associated factors. Results: The guardians had a high HPV vaccine acceptance rate (86.7%) for their girls, and they demonstrated a relatively good level of awareness regarding HPV and HPV vaccines. Factors influencing guardians’ HPV vaccine acceptance for girls included guardians’ education background (OR = 0.57, 95%CI = 0.37–0.87), family income (OR = 1.94, 95%CI = 1.14–3.32), risk of HPV infection (OR = 3.15, 95%CI = 1.40–7.10) or importance of the HPV vaccine for their girls (OR = 6.70, 95%CI = 1.61–27.83), vaccination status surrounding them (OR = 2.03, 95%CI = 1.41–2.92), awareness of negative information about HPV vaccines (OR = 0.59, 95%CI = 0.43–0.82), and recommendations from medical staff (OR = 2.32, 95%CI = 1.65–3.25). Also, guardians preferred to get digital information on vaccines via government or CDC platforms, WeChat platforms, and medical knowledge platforms. Conclusions: Though HPV vaccine willingness was high among Chinese guardians, they preferred to vaccinate their daughters at the age of 17–18 years, later than WHO’s recommended optimal age period (9–14 years old), coupled with safety concerns. Future work should be conducted based on these findings to explore digital intervention effects on girls’ vaccination compliance. Full article

Background/Objectives: Mumps remains a relevant vaccine-preventable disease globally, especially in settings where immunization coverage fluctuates or vaccine-induced immunity wanes. This study aimed to assess long-term trends in mumps incidence, vaccination coverage, clinical outcomes, and demographic characteristics in the Autonomous Province of Vojvodina (AP Vojvodina), Serbia, over a 47-year period. Methods: We conducted a retrospective observational study using surveillance data from the Institute of Public Health of Vojvodina. Analyses included annual mumps incidence rates (1978–2024), coverage with mumps-containing vaccines (MuCVs; 1986–2024), monthly case counts, and individual-level case data for the 1997–2024 period. Variables analyzed included age, month of notification, gender, vaccination status, presence of clinical complications, and the method used for case confirmation. Results: Following the introduction of MuCV in 1986, the mumps incidence markedly declined, with limited resurgences in 2000, 2009, and 2012. Between 1997 and 2024, a total of 1358 cases were reported, with 62.7% occurring in males. Over time, the age distribution shifted, with adolescents and young adults being increasingly affected during the later (2011–2024) observed period. In 2012, the highest age-specific incidence was observed among individuals aged 10–19 and 20–39 years (49.1 and 45.5 per 100,000, respectively). Vaccination coverage for both MuCV doses was suboptimal in several years. The proportion of unvaccinated cases decreased over time, while the proportion with unknown vaccination status increased. Mumps-related complications—such as orchitis, pancreatitis, and meningitis—were rare and predominantly affected unvaccinated individuals: 84.2% of orchitis, 40.0% of pancreatitis, and all meningitis cases. Only two pancreatitis cases (40.0%) were reported after one MMR dose, while fully vaccinated individuals (two doses) had one orchitis case (5.3%) and no other complications. Laboratory confirmation was applied more consistently from 2009 onward, with 49.6% of cases confirmed that year (58 out of 117), and, in several years after 2020, only laboratory-confirmed cases were reported, indicating improved diagnostic capacity. Conclusions: Despite substantial progress in controlling mumps, gaps in vaccine coverage, waning immunity, and incomplete vaccination records continue to pose a risk for mumps transmission. Strengthening routine immunization, ensuring high two-dose MuCV coverage, improving vaccination record keeping, and enhancing laboratory-based case confirmation are critical. Consideration should be given to booster doses in high-risk populations and to conducting a seroepidemiological study to estimate the susceptible population for mumps in AP Vojvodina. Full article

Streptococcus pyogenes (Group A Streptococcus, StrepA) is a human pathogen responsible for hundreds of millions of infections each year and remains one of the most prevalent bacterial causes of upper respiratory and skin infections worldwide. Despite its global impact, there is no approved vaccine, and the optimal protective immune response is still not fully understood. In particular, the role of Th17 T cells in immunity against StrepA remains to be explored. We have previously shown that Th17 T cells are induced in humans following StrepA infection. In this study, we investigated the role of Th17 T cells during skin and upper airway StrepA infections. To generate StrepA-specific Th17 T cells, we utilized a novel cationic liposomal adjuvant system. We demonstrated that vaccine-induced Th17 T cells are recruited to the skin and upper airways upon StrepA infection. In the airways, Th17 T cells and IgA correlate with protection, whereas Th1 T cells and IgG do not. To further characterize the recruited Th17 T cells, we used an IL-17 fate-reporter mouse model to track Th17 T cells. Our results show that Th17 T cells outnumber bona fide Th1 T cells in both StrepA-infected skin and upper airways. Surprisingly, most Th17 T cells lose expression of IL-17, and do not express TNFα, IFNγ, and IL-2. Initial single-cell sequencing data suggest the existence of multiple Th17 T cell subsets with distinct expression profiles. We discuss the functional relevance of these subsets in the context of a StrepA infection. Full article

Antibody titer testing can be useful in controlling successful puppy immunization and can reduce unnecessary vaccinations in adult dogs. We evaluated three commercially available point-of-care tests (POCTs) for detecting antibodies against canine parvovirus (CPV-2), canine distemper virus (CDV) and canine adenovirus (CAV-1 and/or -2), comparing them to the reference virus neutralization (VN) assay. Sera from 200 client-owned dogs (13 healthy, 63 chronically diseased, 124 acute) and 60 specific pathogen-free (SPF) dogs, including 20 sera with maternally derived antibodies (MDA), were tested. All three POCTs demonstrated high sensitivity (79.0–100%) and specificity (97.8–100%) for CPV-2. In contrast, specificity for CDV and CAV was lower with POCT-1 (43.5% and 55.3%) and POCT-2 (42.4% and 79.2%), despite high sensitivity (CDV in both POCTs 98.7%; CAV POCT-1: 99.4%, POCT-2: 90.8%). POCT-3, by comparison, showed high specificity (CDV: 94.1%; CAV: 84.4%) but very low sensitivity (CDV: 17.4%; CAV: 33.1%). Only POCT-1 for CPV-2 detected MDA reliably, whereas the other two POCTs, and POCT-1 for CDV and CAV, did not. When compared to VN, the agreement in vaccination recommendations was 82% for POCT-1 and POCT-2, and 62% for POCT-3. In conclusion, all three POCTs reliably detected antibodies against CPV-2, including MDA with POCT-1. However, the lower specificity for CDV and CAV antibody detection in POCT-1 and POCT-2 raises concerns about misclassifying unprotected dogs as immune, while false-negatives with POCT-3 could lead to unnecessary vaccinations. Further optimization of all three POCTs for CDV and CAV is recommended. Full article

Colorectal cancer (CRC) remains one of the most lethal malignancies worldwide, with high recurrence rates and limited curative options in metastatic settings. Cancer vaccines represent an emerging immunotherapeutic approach that aims to stimulate robust, tumor-specific immune responses. This review summarizes the current state of CRC vaccine development, including tumor cell-based, dendritic cell-based, peptide-based, nucleic acid-based (DNA and mRNA), and virus-based platforms. We highlight findings from key clinical trials that demonstrate immunogenicity, safety, and preliminary efficacy, with particular attention to combinations with chemotherapy and immune checkpoint inhibitors. Furthermore, we explore critical challenges such as tumor heterogeneity, immunosuppressive tumor microenvironments, and the logistical complexity; in this context, we particularly focus on the current development of personalized cancer vaccines, exploring the newly identified encouraging epitopes and their safety and efficacy in recent trials. The integration of cancer vaccines with in silico modeling, advanced delivery systems such as nanoparticles or AI-guided designs, and microbiome modulation represents a promising avenue for enhancing their clinical utility. Overall, therapeutic and prophylactic cancer vaccines may soon contribute meaningfully to the comprehensive management of CRC, especially in settings of minimal residual disease or early recurrence. Full article

Highly pathogenic avian influenza (HPAI) remains a persistent threat to global poultry production and public health. Current vaccine platforms show limited cross-clade efficacy and often fail to induce mucosal immunity. Recent advances in microbiome research reveal critical roles for gut commensals in modulating vaccine-induced immunity, including enhancement of mucosal IgA production, CD8⁺ T-cell activation, and modulation of systemic immune responses. Engineered commensal bacteria such as Lactococcus lactis, Bacteroides ovatus, Bacillus subtilis, and Staphylococcus epidermidis have emerged as promising live vectors for antigen delivery. Postbiotic and synbiotic strategies further enhance protective efficacy through targeted modulation of the gut microbiota. Additionally, artificial intelligence (AI)-driven tools enable predictive modeling of host–microbiome interactions, antigen design optimization, and early detection of viral antigenic drift. These integrative technologies offer a new framework for mucosal, broadly protective, and field-deployable vaccines for HPAI control. However, species-specific microbiome variation, ecological safety concerns, and scalable manufacturing remain critical challenges. This review synthesizes emerging evidence on microbiome–immune crosstalk, commensal vector platforms, and AI-enhanced vaccine development, emphasizing the urgent need for One Health integration to mitigate zoonotic adaptation and pandemic emergence. Full article

Background: Coronavirus disease 2019 (COVID-19) has led to the expansion of the spectrum of invasive fungal infections beyond traditional immunocompromised populations. Although COVID-19-associated pulmonary aspergillosis is increasingly being recognised, COVID-19-associated mucormycosis remains rare, particularly in non-endemic regions. Concurrent COVID-19-associated invasive tracheobronchial aspergillosis and pulmonary mucormycosis with histopathological confirmation is exceedingly uncommon and poses significant diagnostic and therapeutic challenges. Case presentation: We report the case of a 57-year-old female with myelodysplastic syndrome who underwent haploidentical allogeneic haematopoietic stem cell transplantation. During post-transplant recovery, she developed COVID-19 pneumonia, complicated by respiratory deterioration and radiological findings, including a reverse halo sign. Bronchoscopy revealed multiple whitish plaques in the right main bronchus. Despite negative serum and bronchoalveolar lavage fluid galactomannan assay results, cytopathological examination revealed septate hyphae and Aspergillus fumigatus was subsequently identified. Given the patient’s risk factors and clinical features, liposomal amphotericin B therapy was initiated. Subsequent surgical resection and histopathological analysis confirmed the presence of Rhizopus microsporus. Following antifungal therapy and surgical intervention, the patient recovered and was discharged in stable condition. Conclusions: This case highlights the critical need for heightened clinical suspicion of combined invasive fungal infections in severely immunocompromised patients with COVID-19, even in non-endemic regions for mucormycosis. Early tissue-based diagnostic interventions and prompt initiation of optimal antifungal therapy are essential for obtaining ideal outcomes when co-infection is suspected. Full article

Fasciola hepatica remains a global health and economic concern, and treatment still relies heavily on triclabendazole. At the parasite–host interface, F. hepatica calcium-binding proteins (FhCaBPs) have a unique EF-hand/DLC-like domain fusion found only in trematodes. This makes it a parasite-specific target for small compounds and vaccinations. To enable novel therapeutic strategies, we report the first elevated-resolution structure of a full-length FhCaBP4. The apo structure was determined at 1.93 Å resolution, revealing a homodimer architecture that integrates an N-terminal, calmodulin-like, EF-hand pair with a C-terminal dynein light chain (DLC)-like domain. Structure-guided in silico mutagenesis identified a flexible, 16-residue β4–β5 loop (LTGSYWMKFSHEPFMS) with an FSHEPF core that demonstrates greater energetic variability than its FhCaBP2 counterpart, likely explaining the distinct ligand-binding profiles of these paralogs. Molecular dynamics simulations and AlphaFold3 modeling suggest that EF-hand 2 acts as the primary calcium-binding site, with calcium coordination inducing partial rigidification and modest expansion of the protein structure. Microscale thermophoresis confirmed calcium as the major ligand, while calmodulin antagonists bound with lower affinity and praziquantel demonstrated no interaction. Thermal shift assays revealed calcium-dependent stabilization and a merger of biphasic unfolding transitions. These results suggest that FhCaBP4 functions as a calcium-responsive signaling hub, with an allosterically coupled EF-hand–DLC interface that could serve as a structurally tractable platform for drug targeting in trematodes. Full article

Lung cancer remains one of the most prevalent and lethal malignancies worldwide. Although conventional treatments such as surgery, chemotherapy, and radiotherapy have modestly improved patient survival, their overall efficacy remains limited, and the prognosis is generally poor. In recent years, immunotherapy, particularly immune checkpoint inhibitors, has revolutionized cancer treatment. Nevertheless, the immunosuppressive tumor microenvironment, tumor heterogeneity, and immune escape mechanisms significantly restrict the clinical benefit, which falls short of expectations. Within this context, cancer vaccines have emerged as a promising immunotherapeutic strategy. By activating the host immune system to eliminate tumor cells, cancer vaccines offer high specificity, low toxicity, and the potential to induce long-lasting immune memory. These advantages have positioned them as a focal point in cancer immunotherapy research. This paper provides a comprehensive overview of recent clinical advances in lung cancer vaccines, discusses the major challenges impeding their clinical application, and explores potential strategies to overcome these barriers. Full article

Despite the widespread accessibility of vaccines and antivirals, seasonal influenza virus epidemics continue to pose a threat to public health. In this study, we constructed a recombinant replication-deficient simian adenovirus type 25 vector carrying the full-length hemagglutinin (HA) of the H1N1 influenza virus, named rSAd25-H1. Both systemic and mucosal humoral immune responses, as well as the protective efficacy, were assessed in mice immunized via the intramuscular (IM) or intranasal (IN) route. A single-dose IM or IN administration of rSAd25-H1 elicited a robust systemic IgG antibody response, including hemagglutination inhibition antibodies. As expected, only IN immunization was able to induce IgA production in serum and respiratory mucosa. Notably, a single dose of rSAd25-H1 at the highest dose (10¹⁰ viral particles) conferred complete protection against lethal homologous H1N1 challenge in mice despite the route of administration. These findings demonstrate the potential of simian adenovirus type 25-based vectors as a promising candidate for intranasal vaccine development targeting respiratory pathogens. Full article

Background/Objectives: Leukemia is associated with high recurrence rates and cancer vaccines are emerging as a promising immunotherapy against the disease. Here, we investigate the mechanism of action by which a personalized vaccine made from leukemia cells infected with an oncolytic virus (ICV) induces anti-tumor immunity. Methods: Using the L1210 murine model, leukemia cells were infected and irradiated to create the ICV. The CRISPR-Cas9 system was used to engineer knockout cells to test in treatment efficacy studies. Results: We found that pro-inflammatory interferons (IFNs) that are produced by infected vaccine cells induce the immunoproteasome (ImP), a specialized proteasome subtype that is found in immune cells. Interestingly, we show that while a vaccine using the oncolytic vesicular stomatitis virus (oVSV) completely protects against tumor challenge, the wild-type (wt) virus, which does not induce the ImP, is not as effective. To delineate the contribution of the ImP for vaccine efficacy, we generated ImP-knockout cell lines and found no differences in treatment efficacy compared to wild-type cells. Furthermore, an ICV using another murine leukemia model that expresses the ImP only when infected by an IFN gamma-encoding variant of the virus demonstrated similar efficacy as the parental virus. Conclusions: Taken together, our data show that ImP expression by vaccine cells was not required for the efficacy of leukemia ICVs. Full article

Porcine reproductive and respiratory syndrome virus (PRRSV), an enveloped single-stranded positive-sense RNA virus, poses a significant threat to global swine production. Despite the availability of modified live virus and inactivated vaccines, their limited efficacy and safety concerns highlight the urgent need for novel antiviral therapeutics. This study aimed to investigate the molecular mechanisms by which lycopene inhibits PRRSV replication. Initial assessments confirmed that lycopene did not adversely affect cellular viability, cell cycle progression, or apoptosis. Using fluorescence microscopy, flow cytometry, immunoblotting, quantitative real-time PCR (qRT-PCR), and viral titration assays, lycopene was shown to exhibit potent antiviral activity against PRRSV. Mechanistic studies revealed that lycopene suppresses reactive oxygen species (ROS) production, which is critical for PRRSV proliferation. Additionally, lycopene attenuated PRRSV-induced inflammatory responses, as demonstrated by immunoblotting, ELISA, and qRT-PCR assays. These findings suggest that lycopene inhibits PRRSV replication by modulating ROS levels and mitigating inflammation, offering a promising avenue for the development of antiviral therapeutics. This study provides new insights and strategies for combating PRRSV infections, emphasizing the potential of lycopene as a safe and effective antiviral agent. Full article

The repeated occurrence of SARS-CoV-2 variants, largely driven by virus–host interactions, was and will remain a public health concern. Spike protein mutations shaped viral infectivity, transmissibility, and immune escape. From February 2022 to April 2024, a local genomic surveillance program in Verona, Italy, was conducted on 1333 SARS-CoV-2-positive nasopharyngeal swabs via next generation full-length genome sequencing. Spike protein mutations were classified based on their prevalence over time. Mutations were grouped into five categories: fixed, emerging, fading, transient, and divergent. Notably, some divergent mutations displayed a “Lazarus effect,” disappearing and later reappearing in new lineages, indicating potential adaptive advantages in specific genomic contexts. This two-year surveillance study highlights the dynamic nature of spike protein mutations and their role in SARS-CoV-2 evolution. The findings underscore the need for ongoing mutation-focused genomic monitoring to detect early signals of variant emergence, especially among mutations previously considered disadvantageous. Such efforts are critical for driving public health responses and guiding future vaccine and therapeutic strategies. Full article

Despite growing global momentum to reduce the number of children who never received a dose of any vaccine, i.e., zero-dose (ZD) children, persistent geographic and social inequities continue to undermine progress toward universal immunization coverage. In Madagascar, where routine vaccination coverage remains below 50% in most regions, the non-governmental organization Doctors for Madagascar and public sector partners are implementing the SOAMEVA program: a targeted community-based initiative to identify and reach ZD children in sixteen underserved districts in the country’s south. This paper outlines the equity-sensitive evaluation design developed to assess the implementation and impact of SOAMEVA. It presents a forward-looking evaluation framework that integrates both quantitative program monitoring and qualitative community insights. By focusing at the fokontany level—the smallest administrative unit in Madagascar—the evaluation captures small-scale variation in ZD prevalence and program reach, allowing for a detailed analysis of disparities often masked in aggregated data. Importantly, the evaluation includes structured feedback loops with community health workers and caregivers, surfacing local knowledge on barriers to immunization access and program adoption. It also tracks real-time adaptations to implementation strategy across diverse contexts, offering insight into how routine immunization programs can be made more responsive, sustainable, and equitable. We propose eight design principles for conducting equity-sensitive evaluation of immunization programs in similar fragile settings. Full article

The association between COVID-19 vaccination and thromboembolic events has garnered significant research attention, particularly with the advent of vaccines based on adenoviral vectors, including AstraZeneca’s and Johnson & Johnson’s vaccines. This review underscores the uncommon occurrence of venous thromboembolism (VTE), arterial thromboembolism (ATE), and vaccine-induced thrombotic thrombocytopenia (VITT) following COVID-19 vaccination. Although these complications are extremely rare compared to the heightened risk of thrombosis from COVID-19 infection, elements like age, biological sex, type of vaccine and underlying health conditions may contribute to their development. In addition, rare renal complications such as acute kidney injury and thrombotic microangiopathy have been documented, broadening the spectrum of potential vaccine-associated thrombotic manifestations. Current guidelines emphasize early detection, individualized risk assessment, and use of anticoagulation therapy to mitigate risks. Despite these events, the overwhelming majority of evidence supports the continued use of COVID-19 vaccines, given their proven efficacy in reducing severe illness and mortality. In addition, recent comparative data confirm that mRNA-based vaccines are associated with a significantly lower risk of serious thrombotic events compared to adenoviral vector platforms. Ongoing research is essential to further refine preventive and therapeutic strategies, particularly for at-risk populations. Full article