Search Results (939)

Background: Pneumococcal conjugate vaccines (PCVs) have substantially reduced pneumococcal disease in children; however, serotype distribution varies geographically, and residual disease due to non-PCV13 serotypes persists. Biological E’s PNEUBEVAX 14^® (BE-PCV14), a WHO-prequalified 14-valent PCV, expands coverage by including serotypes 22F and 33F. As PCVs are co-administered with routine Expanded Programme on Immunization (EPI) vaccines, post-licensure data on safety, co-administration, and lot-to-lot consistency are essential. This multicenter phase IV study evaluated BE-PCV14 in healthy PCV-naïve infants aged 6–8 weeks across 31 sites in India. Methods: A total of 2600 infants were enrolled and vaccinated at 6, 10, and 14 weeks of age; 2300 received BE-PCV14 and 300 received PCV13. All participants received concomitant DTwP-HepB-IPV-Hib and oral rotavirus vaccines per routine schedule. Safety was assessed through solicited and unsolicited adverse events (AEs) and serious adverse events (SAEs). Immunogenicity subsets evaluated responses to co-administered vaccines and serotype-specific responses across three BE-PCV14 lots. Results: Among 2600 vaccinated infants, at least one AE occurred in 26.35% (95% CI: 24.59, 28.19) of BE-PCV14 and 24.67% (95% CI: 20.13, 29.84) of PCV13 recipients; most were mild. Injection-site pain and pyrexia were the most common events. Immune responses to co-administered vaccines were comparable between groups and met the non-inferiority criteria: lower bound of the two-sided 95% CI > −10 percentage points for seroprotection/seroconversion rate differences using the Farrington–Manning method. Lot-to-lot consistency was demonstrated, with all GMC ratios within the predefined equivalence margin (0.5–2.0). Conclusions: BE-PCV14 was well tolerated. Immune responses to co-administered routine EPI vaccines met predefined non-inferiority criteria, supporting the interpretation that BE-PCV14 did not result in clinically meaningful immune interference. Consistent immune responses across manufacturing lots further support its use in infant immunization programs. Full article

Influenza A virus (IAV) remains a major global health threat despite available vaccines and antiviral agents, while current therapies are limited by drug resistance and safety concerns. Curcuminoids exhibit antiviral and anti-inflammatory activities but are constrained by poor water solubility and low bioavailability. To address these limitations, we investigated the antiviral and immunomodulatory properties of a water-solubilized curcuminoid nanoparticle formulation (C–S/M) in both in vitro and in vivo models of IAV infection. To evaluate the potential antiviral and anti-inflammatory effects of C–S/M, we performed a cytopathic effect (CPE) reduction assay in triplicate at 0.001 MOI and quantitative real-time PCR (qRT-PCR) targeting viral NS1 transcripts in MDCK cells. C–S/M suppressed viral NS1 vRNA levels in MDCK cells at lower curcuminoid-equivalent concentrations than native curcuminoids and attenuated IAV-induced TNF-α, IL-6, and IL-8 production. Furthermore, in vivo antiviral efficacy was evaluated in female C57BL/6 mice intranasally infected with IAV and treated orally with C–S/M. Survival, lung viral loads, pulmonary cytokine levels, and splenic immune cell phenotypes were analyzed. In IAV-infected mice, oral administration of C–S/M modestly improved survival and significantly reduced lung viral burden and pulmonary proinflammatory cytokine levels. In addition, in vivo C–S/M treatment was associated with recovery of virus-suppressed T-cell immune responses, including increased Th1 and activated CD8⁺ T cells, reduced regulatory T-cell expansion, and restoration of multifunctional CD4⁺ and CD8⁺ T cells. These findings suggest that C–S/M exerts antiviral and immunomodulatory effects in experimental IAV infection and may serve as a potential adjunctive candidate for further investigation against influenza-associated inflammation. Full article

Bringing a new drug to market is a complex, costly, and lengthy process, averaging $2.6 billion and about ten years of research and development. It involves multiple stages, from target discovery to post-approval monitoring, and relies heavily on innovation driven by collaboration among pharmaceutical sciences, biology, biochemistry, engineering, and artificial intelligence. Drug discovery can be divided into four main stages: target selection and validation; compound screening and optimization; preclinical studies; and clinical trials. First, researchers identify and validate a biological target associated with a disease using genomic, proteomic, and bioinformatic approaches. Next, potential compounds (“hits”) are identified through methods such as high-throughput and virtual screening, followed by iterative chemical optimization and functional testing. Promising candidates undergo preclinical in vivo studies to assess pharmacokinetics, pharmacodynamics, and toxicity. Clinical development proceeds in three phases: Phase I evaluates safety in healthy volunteers; Phase II assesses efficacy in patients; and Phase III confirms efficacy and safety in larger populations. After successful trials, regulatory agencies review the data for approval. While small molecules have long dominated due to their stability and oral bioavailability, biologics—such as monoclonal antibodies and mRNA-based therapies—have grown rapidly, highlighted by COVID-19 vaccine development and increasing FDA approvals. Full article

Objectives: Parental health literacy plays a pivotal role in shaping caregiving practices and influencing their children’s health. The aim of this systematic review is to analyze studies examining health literacy among parents raising children under five, in relation to caregiving practices and children’s health outcomes. Methods: The research was conducted in accordance with PRISMA protocol. The sample of the study was determined by using the terms related to “health literacy” AND “parent” (OR “caregiver” OR “mother” OR “father”) AND “child” AND “measure” (OR “instrument” OR “tool” OR “questionnaire” OR “survey” OR “interview”) in ERIC, PUBMED, Scopus and WOS databases published between 2015 and 2024. Results: Of the 1726 results identified, 18 studies met the inclusion criteria. The reviewed studies on parental health literacy place particular emphasis on oral health literacy, nutrition/food literacy, vaccine literacy, and fever literacy. Conclusions: Based on the included studies, parents’ health literacy is generally found to be significantly associated with the adequate fulfilment of children’s care needs, the implementation of appropriate parenting practices, and the effective management of childhood illnesses (although findings regarding vaccination willingness are inconsistent). Overall, these associations may carry long-term implications for children’s health. Full article

Most infectious pathogens enter the host through mucosal surfaces, yet conventional injectable vaccines primarily induce systemic immunity without eliciting robust secretory immunoglobulin A (SIgA) responses at mucosal sites. The COVID-19 pandemic highlighted this limitation, as intramuscular mRNA vaccines failed to establish durable mucosal immunity in the upper respiratory tract. This review covers recent progress in mucosal vaccine development. We first discuss the organization of the mucosal immune system, focusing on SIgA induction, tissue-resident memory T (${\mathrm{T}}_{\mathrm{RM}}$) cells, and resident memory B (${\mathrm{B}}_{\mathrm{RM}}$) cells. We then examine mucosal adjuvants, from cholera toxin and heat-labile enterotoxin derivatives to stimulator of interferon gene (STING) agonists and a strategy to enhance alum adjuvanticity through neutrophil elastase inhibition. Delivery routes including intranasal, oral, and sublingual administration are reviewed alongside viral vectors, nanoparticles, mRNA-lipid nanoparticles, virus-like particles, and engineered bacterial platforms. The roles of innate immune cells, T helper cell subsets, and the microbiota in shaping vaccine responses are discussed. Finally, we survey licensed mucosal vaccines and the COVID-19 mucosal vaccine pipeline, analyze persistent barriers to clinical translation including the absence of validated mucosal correlates of protection, and outline future directions for thermostable formulations and systems biology-driven vaccine design. Full article

Background/Objectives: Vaccination is a critical public health intervention, yet its global implementation is hindered by high production costs and cold-chain requirements. This review aims to evaluate plant-based systems as sustainable, cost-efficient alternatives for vaccine production. Methods: A comprehensive literature search was conducted across major databases (PubMed, Scopus, Web of Science). The peer-reviewed references were critically assessed, focusing on molecular expression strategies, phytochemical immunomodulators, and plant-mediated oral delivery. Results: Plant and microalgae systems effectively support nuclear, chloroplast, and transient expression of diverse antigens. Furthermore, specific plant-derived compounds were found to act as potent adjuvants and immunostimulants, enhancing the immunogenicity of vaccine formulations. Edible plant tissues also provide a viable platform for oral delivery, reducing the need for extensive purification and refrigerated logistics. Conclusions: Integrating recombinant expression technologies with bioactive plant metabolites offers a flexible and scalable foundation for next-generation vaccines. These biological platforms show promise for addressing some immunization challenges, particularly in low-resource settings. Full article

Background/Objectives: Poorly soluble aluminium (Al) compounds have successfully been used for decades as adjuvants in vaccines, enabling an effective immune response. Yet the safety of Al exposure from vaccines is consistently questioned, especially regarding infants. Since toxicokinetic data of aluminium after vaccination in humans are not available, model-informed predictions are needed for risk assessment. Methods: Using a physiologically-based toxicokinetic model, we predicted the Al exposure from i.m. injections of Al-adjuvanted vaccines for full-term neonates to 50-year-old adults following the recommended vaccination schedule in Germany 2025 in addition to the continuous oral background Al exposure from dietary intake. Results: During the first two years of life, moderate (max. 2-to-3-fold) but transient increases of Al concentrations in plasma and in the relevant target organs liver and bone due to vaccinations were predicted. Increase in brain Al content was 4%. Most importantly, in all tissues, maximum Al levels did not exceed normal levels observed in infants soon after birth or known from adults. In children and adults, the rise in Al concentrations in plasma and tissues due to single vaccinations was marginal. The calculated contribution of vaccinations to the Al body burden at age 50 was negligible. Conclusions: From a toxicokinetic perspective, the additional Al exposure in full-term infants, children and adults from vaccinations with Al-adjuvanted vaccines according to the current recommended schedules is considered safe. The model has proven a valuable tool for predictions of Al exposure from vaccinations. Full article

Background/Objectives: Bordetella bronchiseptica is a Gram-negative bacterium that, either acting alone or in concert with other bacterial or viral pathogens, is a major cause of the canine infectious respiratory disease (CIRD) complex in dogs. Most currently available vaccines are given intranasally or orally and, whilst providing satisfactory reduction in disease severity, can be difficult to use especially in aggressive or anxious dogs. Whilst a small number of injectable B. bronchiseptica vaccines have been developed, little is known about their characteristics with regard to the age at first vaccination, the onset of immunity, duration of immunity, induction of antibody responses, concurrent use with the core vaccines used in most dogs, efficacy in the face of maternally derived antibodies (MDAs) or existing immunity and safety in pregnant animals. Here we describe the development of a safe and efficacious injectable B. bronchiseptica vaccine that utilises a novel process to purify fimbriae. Methods: The fimbrial antigen was formulated with a vitamin E-based oil-in-water adjuvant known to be safe in dogs (Nobivac^® Respira Bb). To evaluate dose response, thirty-nine naïve 5–6-week-old Beagle puppies were allocated to four groups and vaccinated subcutaneously with Nobivac^® Respira Bb at 69 U, 25 U, and 7 U (with a booster at two weeks). All groups were challenged with B. bronchiseptica two weeks after the booster. To evaluate the onset of immunity at 5–6 weeks of age, twenty-one naïve Beagle dogs were split into two groups: group 1 received Nobivac Respira Bb (88 U/dose) plus Nobivac DHPPi and Nobivac L4; group 2 received DHPPi and L4 only. Both groups were challenged with B. bronchiseptica two weeks after the second vaccination. Safety in pregnancy was evaluated by vaccinating pregnant dams and monitoring whelping outcomes and puppy health. Protection in puppies with maternally derived antibodies (MDAs) was studied in 28 pups (11 MDA-negative and 17 MDA-positive from vaccinated and unvaccinated dams). Pups were vaccinated at 5–6 weeks; one group remained unvaccinated to monitor MDA kinetics. All puppies were challenged with B. bronchiseptica at 19 weeks, after MDAs became undetectable. Serology was monitored throughout; daily clinical observations and nasal swabs post-challenge assessed protection and bacterial shedding. Results: Nobivac Respira Bb (MSD Animal Health), was safe for use in 5–6-week-old puppies alongside other Nobivac core canine vaccines without vaccine interference. The vaccine has an onset of immunity of two weeks and significantly reduces both the clinical signs of B. bronchiseptica-induced disease and bacterial excretion into the environment. Furthermore, the vaccine is equally efficacious in puppies with maternally derived antibodies derived from vaccinated dams and can be used safely in pregnant bitches. Conclusions: This vaccine represents a convenient, safe and efficacious alternative to vaccines delivered via the oral or intranasal routes and is a positive addition to the range of vaccines targeted at reducing disease induced by B. bronchiseptica. Full article

Necrotizing enteritis (NE) is an important intestinal disease threatening the poultry farming industry, and the ban on antibiotic growth promoters has created an urgent demand for safe and effective NE vaccines. Recombinant attenuated Salmonella vectors (RASVs) administered orally can induce mucosal immune responses against delivered antigens, thus showing great potential to elicit protective immunity against NE. The EntB protein is a newly discovered putative enterotoxin of Clostridium perfringens (C. perfringens). Bioinformatic predictions in this study revealed that EntB contains nineteen potential antigenic epitopes, two functional domains (NlpC and YgiM), and interacts with ten proteins, supporting its potential as a target antigen for NE vaccines. To optimize the immunogenicity of EntB-based vaccines, we constructed a novel recombinant attenuated Salmonella Enteritidis (S. Enteritidis) vector rSC0169 harboring a rhamnose-regulated delayed attenuation system, which was then used to deliver EntB to generate the recombinant strain rSC0169(pS-EntB). This system enhanced the immunogenicity of the Salmonella vector rSC0169 and further elicited robust mucosal immune responses against EntB, as well as humoral and cellular immune responses. Compared with the control strain rSC0169(pS0018), rSC0169(pS-EntB) candidate vaccine strain significantly alleviated NE symptoms, increased the intestinal villus height/crypt depth (VH/CD) ratio, upregulated tight junction protein expression, and reduced excessive pro-inflammatory cytokine production. In conclusion, this study provides a promising NE candidate vaccine and offers a valuable strategy for developing vaccines against other intestinal bacterial diseases. Full article

Coronavirus infections pose a significant threat to both human and animal health, causing widespread morbidity, mortality, and substantial economic losses. While vaccines are crucial for prevention, their efficacy is often limited by the high mutation rate of these viruses. This underscores the urgent need for anti-coronavirus drugs, particularly broad-spectrum antiviral agents. In this study, we demonstrated for the first time that Biochanin A (BCA), a bioactive isoflavonoid found in legumes, exhibits broad-spectrum antiviral activity against coronaviruses. BCA potently inhibits porcine epidemic diarrhea virus (PEDV), as well as human coronaviruses HCoV-OC43 and HCoV-229E in vitro, with EC₅₀ values of 6.90, 2.80 and 15.4 μM, respectively. In a lethal mouse model of HCoV-OC43-induced encephalitis, oral administration of BCA (40–60 mg/kg) significantly improved animal survival and reduced cerebral viral loads. Mechanistic studies revealed that BCA upregulates the AMPK/Nrf2 signaling pathway, thereby increasing expression of the glutamate-cysteine ligase catalytic subunit (GCLC) and enhancing glutathione (GSH) biosynthesis. Our findings identify BCA as a promising host-directed antiviral agent and highlight its therapeutic potential against coronavirus infections. Full article

Background: Persistent cervical human papillomavirus (Human papillomavirus) infection remains a significant public health concern, as it is the primary etiological factor in the development of cervical cancer and its precursor lesions. While prophylactic vaccination and standard screening programs are cornerstones of prevention, a substantial proportion of women with established infection are managed conservatively, often with prolonged follow-up and associated psychological burden. Interest has therefore grown in supportive interventions that may facilitate viral clearance during routine clinical management. Methods: This retrospective cohort study included 239 women with confirmed cervical Human papillomavirus infection followed at a tertiary referral center between February 2023 and August 2025. Participants were classified into a treatment group receiving oral Papivir/Pavirona^® twice daily for six months (n = 119) and a control group managed with routine clinical follow-up alone (n = 120). Human papillomavirus DNA testing and cervical cytology were evaluated at baseline and at 6 and 12 months. Results: Human papillomavirus clearance rates were significantly higher in the Papivir/Pavirona^® group compared with controls at both 6 and 12 months. Cytological regression was also more frequent in the treatment group at both time points. In multivariate logistic regression analysis, Papivir/Pavirona^® use emerged as the only independent predictor of both Human papillomavirus clearance and cytological regression, while demographic, reproductive, behavioral, and virological baseline characteristics were not significantly associated with outcomes. Conclusions: Papivir/Pavirona^® supplementation was associated with increased Human papillomavirus clearance and cytological regression rates in women with cervical Human papillomavirus infection, suggesting a potential supportive role alongside standard clinical follow-up. Full article

The rapid expansion of the golden jackal (Canis aureus) across Eastern Europe has reshaped mesocarnivore communities, with potential influence on the dynamics of zoonotic disease. In Romania, where both Trichinella spp. and rabies remain public health concerns, updated data on wildlife reservoirs are essential. This study aims to provide an integrated assessment of Trichinella prevalence and rabies virus-neutralising antibody (RVNA) profiles in 134 wild canids (96 golden jackals and 38 red foxes, Vulpes vulpes) from northwestern Romania (August 2025–January 2026). Trichinella larvae were detected using the artificial digestion method, and infection intensity was expressed as larvae per gram. Rabies serology was performed using a commercial ELISA kit, with 0.5 IU/mL considered the protective threshold. Trichinella prevalence was significantly higher in foxes (78.9%) in comparison with jackals (60.4%), with similar larval burdens in both species. More than half of the individuals in both species exhibited RVNA titers below the protective threshold, indicating heterogeneous immunity levels in the population. No significant age- or sex-related differences in seroconversion were observed. These findings confirm intense sylvatic circulation of Trichinella spp. and highlight potential immunity gaps in wildlife rabies control. The results support the need for integrated, multi-pathogen surveillance and explicit inclusion of the golden jackal in disease monitoring and management strategies. Full article

Background/Objectives: Since 2023, a significant increase in measles cases has been reported worldwide, and Italy has been among the most affected European countries. In this context, the integration of laboratory and epidemiological data enables timely case classification and helps distinguish between imported and indigenous cases, supporting disease control. However, most studies address only selected aspects of surveillance. Therefore, this study aimed to provide an integrated analysis of virological and epidemiological surveillance activities conducted between November 2023 and December 2025 by the Regional Reference Laboratory in the Emilia-Romagna Region (ERR). Methods: A total of 806 clinical samples (269 urine, 267 oral fluids—saliva or oropharyngeal swabs—and 270 sera) from 291 suspected measles cases were tested by molecular and/or serological methods, and MV genotyping was performed. Samples from discarded cases were also analysed for parvovirus B19 (B19V), human herpesvirus 6 (HHV-6), enterovirus (EV), and varicella zoster virus (VZV), chikungunya virus (CHIKV) and dengue virus (DENV). Results: Of 291 suspected cases, 176 (60.5%) were confirmed. Median age was 33 years, with 46% in the 15–39 year group. Vaccination status was available for 165: 90.3% were unvaccinated, 5.4% had one dose, and 4.2% had two doses. Notably, over half of confirmed cases occurred in areas with vaccine-hesitant communities. MV strain characterisation was performed in 99.4% of MV-RNA positive cases, with 84.3% genotype D8 and 15.6% genotype B3; 83% of strains were of indigenous origin, suggesting an ongoing endemic circulation. Clinical data showed complications in 19.3%, mainly pneumonia and diarrhoea. Additionally, differential diagnosis enabled the identification of the etiological agent in 37.5% of measles/rubella discarded cases, and 37.6% (29/77) tested positive for B19V. Conclusions: The study results highlight that effective measles surveillance must be supported by integrating timely virological diagnosis, molecular and epidemiological investigations, and differential diagnosis, to achieve the WHO goals of eliminating measles transmission. Full article

Chicken coccidiosis is a parasitic disease caused mainly by Eimeria tenella, Eimeria acervulina, Eimeria maxima, and Eimeria necatrix, with most cases presenting as mixed infections. Currently, although a subunit vaccine (CoxAbic) targeting Eimeria maxima via maternal immunization is commercially available, no genetically engineered multivalent subunit vaccine exists against mixed infections caused by these four Eimeria species simultaneously. Therefore, we developed a tetravalent recombinant subunit vaccine (designated TEIN) by fusing key antigen genes (TA4, 3-1E, IMP1, NA4) from these four Eimeria species and expressing the construct in Pichia pastoris. A total of 500 chickens were randomly allocated into 25 experimental subgroups (n = 20 each), consisting of five groups (control, challenged, adjuvant, pPIC9K, and TEIN) and five challenge conditions (infection with Eimeria tenella, Eimeria acervulina, Eimeria maxima, Eimeria necatrix, or a mixture of four species). Immunization was performed via leg intramuscular injection at 14 and 21 days of age. At 28 days of age, all chickens except the controls were orally challenged with 1 × 10⁴ sporulated oocysts. Statistical analysis was performed using one-way or two-way ANOVA as appropriate. Results showed that chickens vaccinated with the TEIN subunit vaccine exhibited significantly elevated serum levels of IgY, IL-2, IL-10, and IFN-γ, as well as an increased splenic lymphocyte CD4⁺/CD8⁺ ratio. The anticoccidial indices (ACI) against Eimeria tenella, Eimeria acervulina, Eimeria maxima, and Eimeria necatrix, and their mixed infection reached 174.82, 174.58, 174.41, 180.61, and 175.95, respectively. Moreover, no significant differences were observed in hematological parameters, serum biochemical markers, or histopathological findings between the vaccinated and control groups. These results demonstrate the vaccine’s potential as a promising candidate for controlling mixed coccidial infections. Full article

Diagnostic testing of foot-and-mouth disease virus (FMDV) currently utilizes reverse transcription quantitative PCR (RT-qPCR) to detect the presence of viral RNA and double antibody sandwich ELISAs (DAS-ELISAs) to determine viral serotype. Serotype identification is critical to support informed vaccine selection to combat outbreaks. While DAS-ELISAs are capable of serotype identification, the test suffers from low sensitivity and requires a viral isolate for successful detection. In this study, we developed FMDV-ONTAPS: an Oxford Nanopore Technologies Amplicon P1 Sequencing protocol involving reverse transcription-PCR to amplify P1 of the FMDV genome, and Nanopore sequencing of the amplicons to provide genetic data for serotype and subtype/topotype identification. FMDV isolates representing all seven serotypes were successfully sequenced with this method. Additionally, the protocol successfully provided serotype identification from a variety of specimen matrices obtained from experimentally infected animals that included milk, serum, oral and nasal swabs, tissue suspensions, vesicular fluid, and oral fluid. The limit of detection for FMDV cell culture isolates was comparable for both sequencing and RT-qPCR detection. RT-qPCR Cq values for clinical samples evaluated ranged from 8 to 28.21. Sequencing was successful for all samples except for a single tissue suspension sample (Cq of 28.21). Identification of FMDV serotype in clinical samples is critical for effective outbreak response, and Nanopore sequencing offers a timelier and more sensitive alternative to DAS-ELISAs. Full article