Search Results (935)

Oral, live-attenuated rotavirus vaccines (ORVs) have significantly reduced severe diarrheal disease and deaths; however, vaccine performance in low- and middle-income countries (LMICs) remains lower than in high-income countries. With increasing global use, real-world data now provide important insights into strategies to improve vaccine impact in these settings. This review summarizes current evidence on the effectiveness and impact of ORVs in LMICs, with a focus on approaches to optimize performance, including alternative dosing schedules, booster doses in late infancy, and mixed vaccine regimens. Evidence on vaccine interchangeability offers practical solutions for countries facing supply disruptions and financial constraints. The review also highlights the growing importance of economic sustainability, particularly in the context of transitions from external funding support. Despite lower efficacy, ORVs continue to provide substantial public health benefits in LMICs. Sustained impact will depend on strengthening programme delivery, ensuring stable vaccine supply, and advancing next-generation vaccines. Continued evaluation of effectiveness, cost, and implementation strategies will be critical to maximizing long-term benefits in high-burden settings. Full article

The aquatic pathogen Aeromonas salmonicida SRW-OG1 is responsible for substantial mortality in Epinephelus coioides and many other cultured fish species. This study investigates the contribution of trpE to the pathogenicity of A. salmonicida SRW-OG1 in E. coioides. Specifically, trpE encodes a key enzyme in tryptophan biosynthesis; however, its function in regulating virulence in A. salmonicida remains uncertain. Phenotypic assays indicate that deletion of trpE markedly impaired bacterial growth and significantly reduced multiple virulence-associated traits, including swimming motility, biofilm formation, chemotaxis, hemolytic activity, and extracellular enzyme activity. Transmission electron microscopy revealed that the ΔtrpE mutant lacked flagella, indicating that trpE is involved in flagellar formation or maintenance. In an E. coioides infection model, fish infected with ΔtrpE showed a cumulative survival rate of 48.3%, whereas those infected with the wild-type SRW-OG1 suffered 100% mortality. The ΔtrpE mutant also exhibited reduced bacterial loads in target organs (liver, head kidney, and spleen), while pretreatment with ΔtrpE provided 53.3% protection against a subsequent wild-type challenge. Transcriptomic analysis identified 616 differentially expressed genes, mainly enriched in pathways including flagellar assembly, bacterial chemotaxis, two-component systems, quorum sensing, and biofilm formation. Metabolomic analysis further showed a significant decrease in N-butyryl-L-homoserine lactone, an acyl-homoserine lactone quorum-sensing signal in the ΔtrpE mutant. These findings suggest that trpE contributes to mesophilic A. salmonicida SRW-OG1’s virulence by partially affecting quorum-sensing signal production and motility-related pathways. The attenuated phenotype and protective effect of ΔtrpE indicate its potential as a live attenuated vaccine candidate for controlling A. salmonicida infection in aquaculture. Full article

Background/Objectives: Dementia represents a major global health challenge, and preventive strategies remain limited. Observational studies have suggested a possible association between herpes zoster vaccination (HZV) and dementia risk, although the influence of vaccine type and dose regimen remains unclear. Methods: PubMed, Embase, and Web of Science were searched through January 2026. The primary random-effects meta-analysis included one adjusted estimate per independent study or data-source cluster. Quasi-experimental and correlated secondary estimates were reported separately, and alternative-estimate and leave-one-out analyses retained independent statistical units. The protocol was registered in PROSPERO (CRD420261326042). Results: Fourteen reports representing 13 studies were included. HZV was associated with a lower dementia risk in the primary analysis of five independent data sources (ratio estimate = 0.72; 95% CI: 0.65–0.81; I² = 97.1%), with similar sensitivity results (0.70–0.76). Two regression-discontinuity studies reported eligibility-associated absolute reductions in dementia diagnosis of 1.3 and 1.8 percentage points. Two direct vaccine comparisons favored the recombinant zoster vaccine (RZV; Shingrix) over the live attenuated vaccine (ZVL; Zostavax) (RMTL ratio = 0.83; 95% CI: 0.80–0.87; RR = 0.82; 95% CI: 0.69–0.98). The only direct dose comparison favored two or more RZV doses over one dose (RR = 0.81; 95% CI: 0.74–0.88). Active-comparator associations were generally attenuated, whereas age- and subtype-specific findings varied. These secondary findings were exploratory. Conclusions: HZV was associated with lower dementia risk in observational studies, with directionally consistent quasi-experimental findings. Direct evidence suggested potentially stronger inverse associations for RZV and complete vaccination, but was based on few independent data sources. Substantial heterogeneity and residual confounding preclude causal interpretation, and further prospective or randomized evidence is needed. Full article

Traditional injectable vaccine adjuvants are limited by local granulomatous reactions, chronic inflammation, and reduced compliance, creating an urgent need for safe, host-directed strategies to enhance vaccine immunogenicity. Proanthocyanidins (PACs)—natural polyphenols abundant in grapes, cocoa, and tea—are food-derived bioactive compounds with antioxidant, anti-inflammatory, and immunomodulatory activities, positioning them as attractive candidates for oral immunostimulants. Using classical swine fever virus (CSFV), a Pestivirus within the Flaviviridae that shares conserved genomic and immunological features with human pathogens such as hepatitis C and dengue virus, we systematically evaluated oral PACs (15, 30, and 60 mg/kg/d) combined with attenuated live or subunit CSFV vaccines in mice. PACs were well tolerated across the full dose range, with no impact on body weight or major organs, while selectively increasing the splenic index—suggesting spleen-targeted immune activation without systemic inflammation. Compared with vaccine alone, the moderate dose (30 mg/kg/d) produced the strongest immunostimulation, particularly with the subunit vaccine: peak antigen-specific IgG titer reached 1:409,600, a 4-fold increase versus 1:102,400 for subunit alone and exceeding the 3.4-fold gain observed with the attenuated vaccine. IgG2a and IgG2b rose by 199.4% and 269.1%, respectively, alongside coordinated elevations of Th1 (IL-2 +160.6%, IFN-γ +91.9%) and Th2 (IL-4, IL-10) cytokines, enhanced B- and T-lymphocyte proliferation, and expansion of CD4⁺ and CD8⁺ subsets, establishing a balanced and durable Th1/Th2 response. These findings provide preclinical evidence that food-derived PACs can serve as safe oral immunostimulants for low-immunogenicity subunit vaccines, supporting their further development in human and veterinary vaccinology. Full article

Background: Chikungunya virus (CHIKV) infection is an emerging disease of growing concern to international travelers due to the expanding geographic distribution of competent vectors, climate change, and frequent outbreaks in endemic and previously unaffected regions. Until recently, prevention relied exclusively on vector control and bite prevention; however, the recent approval of chikungunya vaccines has introduced a new preventive strategy. Methods: We conducted a narrative review of currently licensed chikungunya vaccines and candidates in clinical development, focusing on immunogenicity, safety, regulatory status, and implications for travel medicine practice. Results: Two vaccines have recently received regulatory approval: the live-attenuated vaccine IXCHIQ^® and the virus-like particle vaccine Vimkunya^®. Both demonstrated high immunogenicity based on neutralizing antibody thresholds accepted as surrogate markers of protection. Post-marketing safety signals associated with IXCHIQ^®, particularly in older adults, have led to divergent regulatory decisions between authorities. The indication of vaccination in national recommendations varies somewhat depending on age, duration of travel, and individual risk factors. Several additional vaccine platforms remain under investigation, although some candidates have been discontinued. Conclusions: The recent approval of chikungunya vaccines marks a significant milestone in the field of travel medicine. However, uncertainties regarding long-term protection, safety in specific populations, and optimal targeting of travelers remain. Individualized risk–benefit assessment is essential, and further data are needed to refine vaccination strategies for travelers and populations at risk. Full article

Background/Objectives: Mpox (formerly monkeypox) is a re-emerging global health threat. While current vaccines are injectable, oral vaccination offers a painless alternative, though the harsh gastrointestinal (GI) environment challenges live viral vaccines. This study evaluated the stability of orthopoxviruses under simulated GI conditions to assess the physicochemical feasibility of oral mpox immunization. Methods: Attenuated and virulent strains of vaccinia, cowpox, and camelpox viruses were exposed to simulated gastric (pH 1.0–2.0 and 3.0–4.0 with pepsin) and intestinal (pH 7.0–7.5) conditions at 37 °C for 180 min. Viral titers were determined via cell culture assays. The physicochemical protective efficacy of enteric-coated capsules was evaluated using standard dissolution testing parameters. Results: All orthopoxviruses were rapidly inactivated under highly acidic fasting conditions (pH 1.0–2.0). However, they exhibited high stability at pH 3.0–4.0 and 7.0–7.5, retaining approximately 20–30% of their initial infectivity after 180 min. Enteric-coated capsules successfully maintained shell integrity in simulated gastric fluids for over 3 h and dissolved completely under intestinal conditions within ~130 min, aligning with small intestine transit times. Conclusions: Orthopoxviruses possess sufficient intestinal stability to support the physicochemical feasibility of oral immunization, provided they are protected from gastric acidity. Enteric-coated capsules represent a highly suitable delivery system for the intestinal release of live orthopoxvirus-based candidates, warranting further in vivo preclinical evaluation. Full article

Understanding the metabolic basis of bacterial virulence is essential for developing anti-infective strategies. Phosphoenolpyruvate carboxykinase (PEPCK), encoded by pckA, is a key enzyme at the metabolic junction between the pyruvate cycle and the TCA cycle, but its role in virulence regulation remains largely unexplored. In this study, we generated a pckA deletion mutant, ΔpckA, in Edwardsiella tarda and investigated its impact on virulence, metabolism, and vaccine potential. The ΔpckA mutant exhibited increased antibiotic sensitivity, faster growth, reduced autoaggregation, and significantly attenuated virulence in a tilapia infection model. Quantitative proteomics revealed global downregulation of type III and type VI secretion systems (T3SS and T6SS) and upregulation of flagellar proteins. Mechanistically, accumulation of oxaloacetate (OAA) in the mutant suppressed T3SS/T6SS expression without affecting flagellar motility. Importantly, ΔpckA induced a robust immune response in zebrafish and conferred strong protection against lethal challenge, with relative percent survival values of 64% and 81.82% in zebrafish and tilapia, respectively. Taken together, our findings identify PEPCK as a critical metabolic regulator of E. tarda virulence and highlight ΔpckA as a promising live attenuated vaccine candidate. Full article

Toxoplasma gondii is an obligate intracellular apicomplexan parasite that poses serious risks to immunocompromised individuals and the global livestock industry. Our previous study showed that AP2X-1 regulates stage conversion and virulence of T. gondii; however, whether AP2X-1-deficient strains can serve as live-attenuated vaccine candidates is unknown. Here, we evaluated the in vivo virulence, protective efficacy, and induced immunity of the ap2X-1 knockout strain PruΔap2X-1. In Kunming mice, infection with even the highest tested dose (5 × 10⁶ tachyzoites) of PruΔap2X-1 resulted in 100% survival without detectable brain cysts. Vaccination with 10⁶ PruΔap2X-1 tachyzoites conferred complete protection (100% survival) against acute challenge with homologous type II Pru or heterologous ToxoDB#9 PYS strains, whereas control mice exhibited only 0% to 16.7% survival. Moreover, immunized mice orally challenged with Pru cysts showed 100% survival, and no brain cysts were detected under the conditions tested, compared with only 30% survival in control mice challenged with 10 cysts and no survival with 40 cysts. The vaccination induced a Th1-biased response as evidenced by significantly elevated T. gondii-specific total IgG, IgG2a, and the Th1 cytokines IFN-γ and IL-2, along with a significantly reduced IgG1/IgG2a ratio. Collectively, the attenuated PruΔap2X-1 strain generates strong protective immunity against acute and chronic infection with low-virulence strains (the type II Pru and ToxoDB#9 PYS), as well as partial protection against the hypervirulent type I RH strain, positioning it as a potential candidate for a live-attenuated vaccine, with a favorable safety profile observed under the experimental conditions. Full article

Toxoplasmosis, caused by Toxoplasma gondii, remains an important zoonotic disease affecting both human and animal health, particularly in immunocompromised individuals and during pregnancy. Current treatments are unable to eliminate latent tissue cysts and are further limited by adverse effects and prolonged treatment regimens, highlighting the need for effective vaccines. In this study, we evaluated the virulence attenuation and protective efficacy of a CRISPR–Cas9-generated rhoptry protein 64 knockout strain (RHΔrop64) as a live attenuated vaccine candidate in Kunming mice. RHΔrop64 exhibited markedly reduced virulence, and mice tolerated doses of up to 1 × 10² tachyzoites without obvious clinical signs. Immunization provided substantial protection against acute challenge with the parental RHΔku80 and ToxoDB#9 (PYS) strains at 30 days post-vaccination and partial protection against type II (Pru) tachyzoites. In addition, all immunized mice survived following oral challenge with 10 or 40 Pru cysts and exhibited reduced brain cyst burdens among surviving mice. Vaccination also induced measurable humoral and cytokine responses, characterized by increased levels of T. gondii-specific IgG and cytokines that were maintained for at least 75 days post-vaccination. These results suggest that RHΔrop64 has the potential to serve as a live attenuated vaccine candidate, providing substantial, although incomplete, protection against acute challenge with the three T. gondii strains tested and being associated with reduced brain cyst burdens among surviving mice following chronic challenge. Further evaluation is required to determine its safety and applicability as a vaccine candidate for food-producing animals and cats. Full article

African swine fever virus (ASFV) causes African swine fever (ASF), a highly lethal disease in pigs. Vietnam has approved two ASF live-attenuated vaccines (LAVs), but their efficacy and safety remain controversial, and no reliable, highly effective commercial ASF vaccine is available yet. Humoral immunity plays an important role in protection against ASFV infection. However, there is still controversy regarding whether ASFV infection can induce antibodies with neutralizing activity. Antibody-dependent cellular cytotoxicity (ADCC), as an antibody-mediated protective mechanism, offers a novel perspective for screening protective ASFV antigens. This study evaluated five structural proteins (pCP312R, pA104R, pA151R, p17, and pF317L) as subunit vaccine candidates based on their ability to induce antibodies that inhibit viral replication and mediate ADCC. The recombinant proteins were expressed in Escherichia coli, purified, and used to immunize pigs. Immune sera collected two weeks after the third immunization were tested for their ability to inhibit ASFV replication in porcine alveolar macrophages (PAMs) using rASFV-Gluc/EGFP. ADCC activity was assessed using a stable HEK293T-p17 cell line as target cells and porcine peripheral blood mononuclear cells (PBMCs) as effectors, with cytotoxicity measured by lactate dehydrogenase release. All five recombinant proteins were successfully expressed and purified. Immunization with pCP312R, pA104R, p17, and pF317L induced the production of specific antibodies in pigs, but only anti-p17 antibodies significantly inhibited ASFV replication in PAMs. The p17 is highly conserved across different ASFV genotypes and is predicted to contain a transmembrane domain. Anti-p17 antibodies effectively mediated PBMCs to specifically kill target cells, demonstrating significant ADCC activity. Moreover, the HEK293T-p17 cell line was specifically recognized by anti-ASFV sera. These findings indicate that p17 is a dual-functional antigen capable of eliciting antibodies that both inhibit viral replication and mediate ADCC in vitro. Furthermore, we have developed an in vitro platform for screening protective ASFV antibodies based on viral inhibition and ADCC, providing candidate targets for the development of next-generation ASF subunit vaccines. Full article

Autophagy is a crucial mechanism in the host response to intracellular bacterial pathogens during which microorganisms may undergo direct degradation in autophagolysosomes. As a highly virulent intracellular pathogen, Francisella tularensis has developed survival strategies to escape from the phagosome, replicate in the cytosol of mononuclear cells, and avoid degradation within the double-membrane vacuole during the autophagy-mediated response. The aim of this study was to investigate the role of the ATG5 autophagy protein in the host immune response to Francisella tularensis subsp. holarctica, live vaccine strain (LVS), since ATG5 plays an important role in autophagosome formation during canonical autophagy. In vitro experiments were conducted on immortalized bone marrow macrophages subjected to starvation-induced autophagy. Transgenic mice deficient in ATG5 of cells of the myeloid lineage (monocytes/macrophages and granulocytes) were used to analyze the immunological responses after intradermal infection. Cytokine levels were analyzed using Luminex, RT-qPCR, and ELISA, while inflammatory cell infiltration in the lung was analyzed by immunohistochemistry. Our results demonstrate that induced autophagy decreased bacterial replication in vitro. However, ATG5 deficiency in myeloid cells in vivo significantly diminished levels of pro-inflammatory cytokine IFN-γ in the sera, spleen, liver, and lung during Francisella infection. The attenuated pro-inflammatory response also led to significantly reduced macrophage and T cell infiltration in the lung tissue. Our findings also reveal that neutralization of IL-1β in myeloid ATG5ΔMye mice increased susceptibility to tularemia by increasing bacterial burden in organs. Full article

A field trial was conducted on a single commercial swine farm to compare the integrated control efficacy of an inactivated vaccine and a live attenuated vaccine against mycoplasmal pneumonia of swine (MPS). Mhp exposure in the herd was confirmed by qPCR prior to trial initiation. Initially, 30 five-day-old piglets were randomly assigned to three groups (10 piglets per group): non-immunized control, inactivated vaccine, and live attenuated vaccine, for clinical safety evaluation. Based on this, another 900 five-day-old piglets, confirmed Mhp-negative by antigen detection, were randomly allocated to three separate rearing zones (300 piglets per zone), with each zone randomly assigned to one of the three treatment groups. Parameters assessed included mucosal (sIgA) and serum (IgG) antibody levels, pulmonary inflammatory cytokine (e.g., IL-1β, IL-6, TNF-α) expression, lung lesion scores, and histopathological changes, with all evaluations performed by technicians blinded to group allocation. Growth performance and economic indicators were also recorded. Both vaccines exhibited favorable safety profiles. The live attenuated vaccine significantly enhanced nasal sIgA and serum IgG levels (p ≤ 0.01), whereas the inactivated vaccine only significantly elevated serum IgG (p ≤ 0.01) but had no significant effect on sIgA (p ≥ 0.05). The live attenuated vaccine group showed the lowest lung lesion scores, as well as the mildest pulmonary inflammation and pathological damage. Meanwhile, swine in this group achieved higher average daily gain, lower mortality, and lower feed conversion ratio, with a 3-day shorter rearing period than the non-immunized group and an 11.27 CNY reduction in combined vaccination and medication cost per swine compared with the inactivated vaccine group. In conclusion, under the conditions of this single-farm trial, the live attenuated vaccine demonstrated superior efficacy in integrated MPS control and production performance improvement. Full article

Background: Equine herpesvirus type 1 (EHV-1) and equine influenza virus (EIV) are major respiratory pathogens in horses, causing significant economic losses in domesticated horses. Bacterial Artificial Chromosome (BAC) technology can be used to precisely manipulate the EHV-1 genome for the development of live-attenuated vector vaccines. Earlier, our group developed a live-attenuated EHV-1 vaccine by deleting virulence-associated genes using this technology and the mutant EHV-1 has been exploited for expressing foreign gene in the current study. Specifically, in this study, a mutant EHV-1 virus expressing the hemagglutinin (HA) gene of H3N8 EIV (sub-lineage: Florida clade 2) was generated and characterized in vitro. Methods: The HA gene of EIV (Florida clade 2) was used for antigen gene cloning. The expression cassette for the HA gene was commercially synthesized and inserted into the backbone of EHV1∆IR6 BAC using an En passant mutagenesis strategy. Recombinant clones were selected using antibiotic selection, PCR, and RFLP. Further, the recombinant virus was regenerated in RK-13 cells via transfection and characterized in vitro for plaque size, growth kinetics and immunofluorescence antibody test (IFAT). Results: PCR and RFLP confirmed the successful insertion of the HA gene into pEHV1∆IR6/gE BAC. The recombinant virus, vEHV1∆IR6/gE-HA(FC2), was successfully rescued in RK13 cells and demonstrated expression of the EIV haemagglutinin proteins by immunofluorescence assay. Although plaque size was reduced in the generated mutant virus in comparison to parental virus, the growth kinetics of the recombinant viruses were comparable to those of vEHV1∆IR6/gE. Conclusions: These findings demonstrate the successful expression of immunodominant hemagglutinin protein of EIV by recombinant EHV-1 and indicate the potential suitability of EHV-1 BAC as a vector platform for foreign gene expression. Full article

Recent advances in vaccinology have accelerated the shift from conventional live-attenuated and inactivated vaccines toward subunit and nucleic acid-based platforms. Although these next-generation vaccines offer improved safety, rapid adaptability, and manufacturing flexibility, their relatively low intrinsic immunogenicity often requires efficient adjuvants and delivery systems. Nanoparticle-based vaccine platforms have therefore emerged as versatile tools capable of protecting antigens, improving targeted delivery, and modulating both innate and adaptive immune responses. This review summarizes the major classes of nanovaccine platforms, including lipid and polymeric nanoparticles, self-assembling protein nanostructures such as virus-like particles and ferritin nanocages, saponin-based self-assembling complexes, and inorganic nanomaterials. Particular attention is given to how vaccine performance is determined not only by material composition but also by nanoparticle physicochemical properties, biodistribution, cellular uptake, and mechanisms of immune activation. We further discuss the major challenges limiting clinical translation, including scalable manufacturing, safety evaluation, quality control, regulatory requirements, and long-term biocompatibility. Finally, emerging strategies involving hybrid and personalized nanovaccine platforms are highlighted, illustrating how nanotechnology and immunoengineering are transforming vaccine development for both prophylactic and therapeutic applications. Full article

Background/Objectives: We describe the rationale, design and evaluation of a novel feline combination vaccine (Nobivac^® NXT HCPChFeLV) incorporating RNA particle technology against feline leukemia virus (FeLV) alongside live attenuated components for feline herpesvirus-1 (FHV), feline calicivirus (FCV), feline panleukopenia (FPL) and Chlamydia felis. Efficacy and safety outcomes from laboratory and field studies are presented. Methods: Nobivac NXT HCPChFeLV is a 0.5 mL, non-adjuvanted, lyophilized vaccine containing live attenuated FHV, FCV, FPL, and C. felis strains, and an alphavirus replicon-derived RNA particle expressing FeLV envelope glycoprotein (gp85). The primary vaccination schedule involved subcutaneous vaccination at 8–9 weeks of age with a booster 4 weeks later. Onset-of-immunity studies were performed 1 week post primary vaccination. Duration-of-immunity studies evaluated challenge both at 1 year and 3 years after primary vaccination with a booster at 1 year (FHV, FCV, FeLV); FPL duration was assessed at 3 years after primary vaccination; C. felis duration was assessed at 1 year. Clinical signs of disease, survival, leukopenia (FPL) and pathogen excretion were assessed. Safety was assessed in laboratory overdose/repeat-dose studies and in a field study comparing concurrent (non-mixed) use with rabies vaccination vs a positive control regimen. Results: Vaccination significantly reduced clinical disease following FHV, FCV and C. felis challenge and reduced FHV-associated mortality. Vaccinated cats were protected from FPL clinical disease, mortality, leukopenia, and FPL excretion. Persistent FeLV antigenemia was significantly prevented after primary vaccination and in 1-year-duration-of-immunity studies and was reduced 3 years after revaccination. The excretion of FHV, FCV and C. felis was significantly reduced in vaccinates vs controls. No serious adverse events were observed in laboratory studies; field vaccination was well tolerated with no injection-site reactions reported. Conclusions: Nobivac NXT HCPChFeLV provides robust, long-lasting protection against multiple feline pathogens, reduced pathogen shedding and demonstrated a favorable safety profile, supporting its use in feline preventive healthcare. Full article