Search Results (24,008)

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

Porcine circovirus type 2 (PCV2) is a globally prevalent swine pathogen that induces immunosuppression, predisposing pigs to subclinical infections. In intensive farming systems, PCV2 persistently impairs growth performance and vaccine efficacy, leading to substantial economic losses in the swine industry. Emerging evidence suggests that certain viruses exploit Suppressor of Cytokine Signaling 3 (SOCS3), a key immune checkpoint protein, to subvert host innate immunity by suppressing cytokine signaling. While SOCS3 has been implicated in various viral infections, its regulatory role in PCV2 replication remains undefined. This study aims to elucidate the mechanisms underlying the interplay between SOCS3 and PCV2 during viral pathogenesis. Porcine SOCS3 was amplified using RT-PCR and stably overexpressed in PK-15 cells through lentiviral delivery. Bioinformatics analysis facilitated the design of three siRNA candidates targeting SOCS3. We systematically investigated the effects of SOCS3 overexpression and knockdown on PCV2 replication kinetics and host antiviral responses by quantifying the viral DNA load and the mRNA levels of cytokines. PCV2 infection upregulated SOCS3 expression at both transcriptional and translational levels in PK-15 cells. Functional studies revealed that SOCS3 overexpression markedly enhanced viral replication, whereas its knockdown suppressed viral proliferation. Intriguingly, SOCS3-mediated immune modulation exhibited a divergent regulation of antiviral cytokines: PCV2-infected SOCS3-overexpressing cells showed elevated IFN-β but suppressed TNF-α expressions, whereas SOCS3 silencing conversely downregulated IFN-β while amplifying TNF-α responses. This study unveils a dual role of SOCS3 during subclinical porcine circovirus type 2 (PCV2) infection: it functions as a host-derived pro-viral factor that facilitates viral replication while simultaneously reshaping the cytokine milieu to suppress overt inflammatory responses. These findings provide novel insights into the mechanisms underlying PCV2 immune evasion and persistence and establish a theoretical framework for the development of host-targeted control strategies. Although our results identify SOCS3 as a key host determinant of PCV2 persistence, the precise molecular pathways involved require rigorous experimental validation. Full article

Background/Objectives: Typically, studies aiming to assess the ability of canine parvovirus (CPV) vaccines to immunise puppies with maternally derived antibody (MDA) are undertaken using group-housed puppies. Since live attenuated vaccine virus is invariably shed in the faeces, this can result in repeated oral re-exposure and puppies which failed to respond to the initial vaccination may respond instead to shed vaccine virus in the environment, thus artificially enhancing the efficacy of the vaccine. This problem can be avoided by adopting a pair-housed study design where one vaccinated pup is housed with one unvaccinated sentinel. Using this design, we examine the capability of four commercially available canine parvovirus vaccines to immunise MDA-positive pups. Methods: Thirty-four 6-week-old puppies born to vaccinated dams were divided into four vaccine groups with similar MDA ranges. Within each group puppies were paired based on matching MDA titres, and each pair was housed in separate biocontainment accommodation. In each pair, the pup with the highest MDA was vaccinated and the other left as an unvaccinated sentinel. All vaccinates were given a single dose of one of the vaccines. Vaccinates and sentinels were then bled every 2–4 days and CPV antibody was measured. Daily rectal swabs were also collected from all pups to identify any shed vaccinal CPV. Results: All the pups vaccinated with Nobivac DP PLUS seroconverted, with significantly higher antibody titres compared to the pups in other vaccine groups, all shed vaccine virus, and all bar one of the sentinel pups seroconverted. In the other groups, only vaccinated pups with lower levels of MDA seroconverted and shed vaccine virus but none of the sentinel pups seroconverted. Conclusions: Different canine parvovirus vaccines differ in their ability to replicate in and immunise puppies with MDA, the levels of which may vary widely between individuals. The shedding of vaccinal CPV is an important consideration when designing studies to demonstrate efficacy in MDA-positive puppies. Full article

The impact of Oedema Disease produced by Shiga toxigenic Escherichia coli (STEC) in swine is increasing in some production countries due to increasing limitations on treatment with antimicrobials and zinc oxide, either because of the increased prevalence of multi-resistant strains or because of legal restrictions. The main pathological effect of Shiga toxin 2e is represented by damage to the endothelial cells of the blood vessel walls, leading to liquid extravasation and oedema formation in multiple tissues. These oedemas are generally easily identifiable in acute clinical cases. However, disease caused by Shiga toxin can occur without any externally visible oedema in the pigs, as observed in the subclinical presentation of Oedema Disease. It also causes productive losses, so it is important to identify and/or diagnose cases to set up control measures in order to optimize production and health. This article includes a comprehensive review of lesions and signs caused by Shiga toxin toxicosis in pigs, as well as other insights about the aetiology and epidemiology of STEC in pigs, and the effect of Shiga toxin recombinant toxoid vaccines in reducing these clinical and subclinical signs under field conditions. Full article

Background: It is still challenging to develop effective vaccines against tumorigenic human gammaherpesviruses such as Epstein–Barr virus (EBV). A major obstacle is the lack of a small animal model that reproduces the natural infection course of human gammaherpesviruses to allow for proper assessment of vaccine efficacy. Murine gammaherpesvirus 68 (MHV68) is a natural pathogen of wild rodents and laboratory mice and therefore can be used as a surrogate for human gammaherpesviruses to evaluate vaccination strategies. Methods: In this study, two mRNA vaccine candidates were generated, one encoding a fusion protein of the MHV68 gH with the gL (gHgL-mRNA) and the other expressing the MHV68 gB protein (gB-mRNA). The immunogenicity and protective efficacy of the mRNA vaccine candidates were evaluated in a mouse model of MHV68 infection. Results: The gHgL-mRNA but not the gB-mRNA candidate vaccine was able to induce neutralizing antibodies in mice, whereas both vaccines could elicit antigen-specific T-cell responses. Following MHV68 intranasal inoculation, complete blocking of the establishment of viral latency was observed in some mice immunized with individual gHgL-mRNA or gB-mRNA vaccines. Notably, co-immunization with the two mRNA vaccines appeared to be more effective than individual vaccines, achieving sterile immunity in 50% of the vaccinated mice. Conclusions: This study demonstrates that immunization with mRNA platform-based subunit vaccines is indeed capable of preventing MHV68 latent infection, thus validating a safe and efficacious vaccination strategy that may be applicable to human gammaherpesviruses. Full article

Background/Objective: The COVID-19 pandemic profoundly transformed social life worldwide, indiscriminately affecting individuals across all age groups. Children have not been exempted from the risk of severe illness and death caused by COVID-19. Objective: This paper sought to describe the clinical findings, laboratory and imaging results, and hospital care provided for severe and critical cases of COVID-19 in unvaccinated children, with or without severe asthma, hospitalized in a public referral service for COVID-19 treatment in the Brazilian state of Pernambuco. Methods: This was a case series study of severe and critical COVID-19 in hospitalized, unvaccinated children, with or without severe asthma, conducted in a public referral hospital between March 2020 and June 2021. Results: The case series included 80 children, aged from 1 month to 11 years, with the highest frequency among those under 2 years old (58.8%) and a predominance of males (65%). Respiratory diseases, including severe asthma, were present in 73.8% of the cases. Pediatric multisystem inflammatory syndrome occurred in 15% of the children, some of whom presented with cardiac involvement. Oxygen therapy was required in 65% of the cases, mechanical ventilation in 15%, and 33.7% of the children required intensive care in a pediatric intensive care unit. Pulmonary infiltrates and ground-glass opacities were common findings on chest X-rays and CT scans; inflammatory markers were elevated, and the most commonly used medications were antibiotics, bronchodilators, and corticosteroids. Conclusions: This case series has identified key characteristics of children with severe and critical COVID-19 during a period when vaccines were not yet available in Brazil for the study age group. However, the persistence of low vaccination coverage, largely due to parental vaccine hesitancy, continues to leave children vulnerable to potentially severe illness from COVID-19. These findings may inform the development of public health emergency contingency plans, as well as clinical protocols and care pathways, which can guide decision-making in pediatric care and ensure appropriate clinical management, ultimately improving the quality of care provided. Full article

Background: Patients with resected stage IIB and IIC melanoma are at high risk of recurrence and distant metastasis, despite surgical treatment. The recent emergence of immune checkpoint inhibitors (ICIs) has led to their evaluation in the adjuvant setting for early-stage disease. This review aims to synthesize current evidence regarding adjuvant immunotherapy for stage IIB/IIC melanoma, explore emerging strategies, and highlight key challenges and future directions. Methods: We conducted a comprehensive literature review of randomized clinical trials, observational studies, and relevant mechanistic and biomarker research on adjuvant therapy in stage IIB/IIC melanoma. Particular focus was placed on pivotal trials evaluating PD-1 inhibitors (KEYNOTE-716 and CheckMate 76K), novel vaccine and targeted therapy trials, mechanisms of resistance, immune-related toxicity, and biomarker development. Results: KEYNOTE-716 and CheckMate 76K demonstrated significant improvements in recurrence-free survival (RFS) and distant metastasis-free survival (DMFS) with pembrolizumab and nivolumab, respectively, compared to placebo. However, no definitive overall survival benefit has yet been shown. Adjuvant immunotherapy is linked to immune-related adverse events, including permanent endocrinopathies. Emerging personalized approaches, such as circulating tumor DNA monitoring and gene expression profiling, may enhance patient selection, but remain investigational. Conclusions: Adjuvant PD-1 blockade offers clear RFS benefits in high-risk stage II melanoma, but optimal patient selection remains challenging, due to uncertain overall survival benefit and toxicity concerns. Future trials should integrate biomarker-driven approaches to refine therapeutic decisions and minimize overtreatment. Full article

Vaccination is the most effective method to counteract infectious diseases in farmed fish. It secures aquaculture production and safeguards the wild stock and aquatic ecosystem from catastrophic contagious diseases. In vaccine development, recombinant subunit vaccines are favorable candidates since they can be economically produced in large quantities without growing many pathogens, as in inactivated or attenuated vaccine production. However, recombinant subunit vaccines are often weak or deficient in immunogenicity, resulting in inadequate defenses against infections. Technologies that can increase the immunogenicity of recombinant subunit vaccines are in desperate need. Enhanced green fluorescence protein (EGFP) has a low antigenicity and is susceptible to folding changes and losing fluorescence after fusing with other proteins. Using these valuable features of EGFP, we comprehend two amphipathic alpha-helical peptides, AH1 and AH3, derived from Hepatitis C virus and Influenza A virus, respectively, that can induce high immune responses of their fused EGFP in fish without affecting their folding. AH3-EGFP has the most elevated cell binding, significantly 62% and 36% higher than EGFP and AH1-EGFP, respectively. Immunizations with AH1-EGFP or AH3-EGFP significantly induced higher anti-EGFP antibody levels 300–500-fold higher than EGFP immunization after the boost injection in rainbow trout. Our results suggest that AH1 and AH3 effectively increase the immunogenicity of EGFP without influencing its structure. Further validation of their value in other recombinant proteins is necessary to demonstrate their broader utility in enhancing the immunogenicity of subunit vaccines. We also suggest that EGFP and its variants are promising candidates for initially screening proper immunogenicity-enhancing peptides or proteins to advance recombinant subunit vaccine development. Full article