Search Results (23,568)

Background: Bovine respiratory syncytial virus (BRSV) is a major pathogen of the bovine respiratory disease complex and causes regular severe winter outbreaks of respiratory disease in cattle. It is therefore responsible for important economic losses for the farming industry. In this study, the genetic diversity of the circulating BRSV strains in Belgium, which has not been assessed since the end of the 1990s, was investigated. Methods: We analyzed 51 BRSV-positive samples collected from 2015 to 2023. This study is the first report on the circulation of BRSV subgroup VIII in Belgium. Furthermore, co-circulation of subgroups II and III was recorded in the same period. Four commercially available vaccine strains marketed in Belgium were also included in the analysis and they clustered with subgroup II or III. Results: Our findings indicate that different strains of BRSV are circulating in Belgium, including those from subgroups II and VIII, with the subgroup VIII strains being particularly distant from the commercially available vaccine strains. Conclusions: These results highlight the importance of ensuring that the available vaccines efficiently protect against strains from circulating subgroups and assessing the potential circulation of attenuated vaccine strains. Full article

In August 2020, the World Health Assembly approved the global strategy to eliminate cervical cancer, envisioning a world where it seizes to be a public health problem. The cervical cancer elimination initiative reinforces the commitment to fulfilling the rights of adolescent girls and women by reducing both health and economic inequities in the poorest populations that have more limited access to timely and effective services. This initiative improves the quality of life of women and their families by protecting them from a disease that causes disability and preventing avoidable mortality through public health measures. This article discusses the epidemiological situation and vaccination coverage and identifies weaknesses and opportunities in Latin America and the Caribbean to propose actions to reinforce progress toward the cervical cancer elimination goal. Full article

Background: The therapeutic blockade of the PD1/PD-L1 axis with monoclonal antibodies has led to a breakthrough in cancer treatment, as it plays a key role in the immune evasion of tumors. Nevertheless, treating patients with cancer with vaccines that stimulate a targeted immune response is another attractive approach for which few side effects have been observed in combination immunotherapy clinical trials. In this sense, our group has recently developed a therapeutic cancer vaccine candidate called PKPD-L1^Vac which contains as an antigen the extracellular domain of human PD-L1 fused to a 47 amino-terminal, part of the LpdA gene of N. meningitides, which is produced in E. coli. The investigation of potential toxicities associated with PD-L1 blockade by a new therapy in preclinical studies is critical to optimizing the efficacy and safety of that new therapy. Methods: Here, we describe immunogenicity and preliminary safety studies in mice, rats, rabbits, and non-human primates that make use of a 200 μg dose of PKPD-L1 in combination with VSSPs or alum phosphate to contribute to the assessment of potential adverse events that are relevant to the future clinical development program of this novel candidate. Results: The administration of PKPD-L1^Vac to the four species at the doses studied was immunogenic and did not result in behavioral, clinical, hematological, or serum biochemical changes. Conclusions: Therefore, PKPD-L1^Vac could be considered suitable for further complex toxicological studies and the way for its clinical evaluation in humans has been opened. Full article

Recurrent urinary tract infection (rUTI) is a significant public health problem in women. General measures to prevent recurrence include behavioral changes and increased fluid intake, cranberry ingest, use of methenamine hippurate, antibiotic prophylaxis, D-mannose, probiotics, or vaccines. We conducted a literature review of the latest updates on preventing rUTI in December 2024. The search concluded with 27 articles that fulfilled our inclusion criteria. Our review demonstrated that behavioral changes such as correct genital hygiene, avoiding postponing micturition or defecation, urinating after sexual intercourse, and ingesting 1.5–2 L of water could prevent rUTI. The ingestion of cranberries reduces the risk of symptomatic, culture-verified urinary tract infections in women with rUTIs. Methenamine hippurate is an alternative to antibiotics to avoid rUTI. Estrogen reduces rUTI in women with hypoestrogenism. Limited evidence supports using D-mannose, probiotics, and vaccines to prevent rUTI. In conclusion, after successful treatment of the acute episode, preventative measures are needed to reduce rUTI frequency and morbidity according to each patient’s characteristics and preferences. Full article

Background: Various factors influence the immunologic responses to HBV vaccines in adults, including unchangeable individual characteristics. Personalized vaccination regimens accounting for host factors can enhance immune efficiency, particularly for adults at higher risk. Methods: In this two-center controlled trial, HBV vaccine-naïve participants aged 25–55 were randomly administered the two types of HBV vaccines (yeast cell-derived (YDV) or Chinese hamster ovary (CHO) cell-derived) at 0–1–6 months. Antibody titers were measured eight weeks after the final dose. Results: Overall, 289 participants with YDV and 293 participants with CHO completed the three-dose series and antibody testing. The seroprotection rates (SPRs) were comparable (97.23% vs. 98.98%; p = 0.1398), but the geometric mean concentration (GMC) was significantly higher for the CHO (1627.83 mIU/mL vs. 600.76 mIU/mL; p < 0.0001). The GMC of both regimens declined significantly in individuals aged ≥45 years and males. Unlike the YDV, the GMC of CHO was minimally affected by BMI or smoking or drinking status. Conclusion: The CHO regimen may be advantageous for HBV vaccine-naïve adults aged 25–55 with BMI ≥ 25 or those who smoke or drink, in terms of immunogenicity and durability, providing insights for personalized immunization strategies. Full article

Background/Objectives: Targeted delivery of antigens to dendritic cells (DCs) is an effective strategy for enhancing vaccine efficacy. Methods: In this study, dual-targeting fusion proteins (GRFT-VHH54 and GRFT-VHH74) were constructed by fusing Griffithsin (GRFT), an algae-derived lectin with enveloped virus-binding properties, to DC-specific binding nanobodies (VHH54 and VHH74). Vaccines were formulated by combining the inactivated H9N2 avian influenza virus with these fusion proteins, and the potential of the fusion proteins to enhance vaccine-induced immunity in chickens was systematically evaluated. For parallel comparison, control groups included H9N2 avian influenza vaccines containing the inactivated virus alone, the inactivated virus with the immune enhancer CVCVA5, and a commercial H9N2 avian influenza inactivated vaccine. Results: At 4 weeks post-immunization, chickens vaccinated with the inactivated H9N2 virus combined with the GRFT-VHH74 fusion protein (1/2 H9+GRFT-VHH74) exhibited significantly enhanced humoral, mucosal, and cellular immune responses compared to those vaccinated with the inactivated H9N2 virus alone or the commercial H9N2 vaccine (p < 0.05). Additionally, chickens in the 1/2 H9+GRFT-VHH74 group exhibited enhanced resistance to the heterologous H9N2 subtype avian influenza virus, achieving a 90% protection rate, which was higher than that of the other groups. Conclusions: These results indicate that the GRFT-VHH74 fusion protein has significant potential for advancing the development of inactivated vaccines against the H9N2 subtype avian influenza. Furthermore, it provides valuable insights for enhancing the immunogenicity and efficacy of inactivated vaccines targeting other avian influenza subtypes. Full article

Background: The aim of this study was to evaluate whether increased body mass index (BMI) and biochemical and lifestyle parameters linked to obesity and smoke exposure disrupt immune responses of children and adolescents following vaccination with the mRNA BNT162b2 vaccine. Methods: A prospective, single-center, cohort study was conducted. Participants were assigned to receive two doses of the mRNA vaccine. Anti-SARS-CoV-2 IgG and neutralizing antibodies (AB) were measured before vaccination (T0) and 14 days after the second dose (T1). BMI and biochemical parameters were evaluated at T0. A questionnaire on lifestyle characteristics was filled in. Results: IgG optical density (OD) ratio at T1 was lower in the overweight–obese group regardless of COVID-19 disease positive history [p = 0.028 for the seronegative group, p = 0.032 for the seropositive group]. Neutralizing AB were lower in overweight–obese participants in the seronegative group at T1 [p = 0.008]. HDL, fasting glucose/insulin ratio (FGIR), C-reactive protein (CRP), HBA1c, uric acid, and smoke exposure were significantly correlated with BMI [p = 0.006, p < 0.001, p < 0.001, p = 0.006, p = 0.009, p < 0.001, respectively]. The main biochemical parameters that were inversely correlated with IgG and neutralizing AB titers at T1 were uric acid [p = 0.018, p = 0.002], FGIR [p = 0.001, p = 0.008] and HBA1C [p = 0.027, p = 0.038], while smoke exposure negatively affected the humoral immune responses at T0 in the convalescent group [p = 0.004, p = 0.005]. Conclusions: Current data suggests that uric acid, insulin resistance (IR), and smoke exposure could adversely affect the immune responses in overweight–obese vaccinated children, highlighting the need for actions to enhance the protection of this particular subgroup. Full article

Background. The pathogenic coronaviruses (CoVs) MERS-CoV and SARS-CoV-2, which are responsible for the MERS outbreak and the COVID-19 pandemic, respectively, continue to infect humans, with significant adverse outcomes. There is a continuing need to develop mucosal vaccines against these respiratory viral pathogens to prevent entry and replication at mucosal sites. The receptor-binding domain (RBD) of the CoV spike (S) protein is a critical vaccine target, and glycan masking is a unique approach for designing subunit vaccines with improved neutralizing activity. Methods. We evaluated the efficacy of mucosal immunity, broad neutralizing activity, and cross-protection afforded by a combined glycosylated mucosal subunit vaccine encoding the RBDs of the original SARS-CoV-2 strain (SARS2-WT-RBD), the Omicron-XBB.1.5 variant (SARS2-Omi-RBD), and MERS-CoV (MERS-RBD). Results. Intranasal administration of the three-RBD protein cocktail induced effective, durable IgA and systemic IgG antibodies specific for the S protein of these CoVs, thereby neutralizing infection by pseudotyped SARS-CoV-2-WT, Omicron-XBB.1.5, and MERS-CoV. The mucosal vaccine cocktail protected immunized mice from challenge with SARS-CoV-2 Omicron-XBB.1.5 and MERS-CoV, leading to a significant reduction in the viral titers in the lungs. By contrast, the individual glycosylated RBD proteins only induced such immune responses and neutralizing antibodies against either SARS-CoV-2 or MERS-CoV, protecting against subsequent challenge with either SARS-CoV-2 or MERS-CoV; they did not provide simultaneous protection against both CoVs. Conclusions. This study describes a unique strategy for designing efficacious mucosal subunit vaccines that induce durable mucosal immunity, cross-neutralizing activity, and cross-protection against SARS-CoV-2 and MERS-CoV, highlighting the potential for the design of mucosal vaccines against other pathogens. Full article

Phosphoinositide 3-kinases (PI3Ks), members of the lipid kinase family, play a significant role in modulating immune cell functions, including activation, proliferation, and differentiation. Recent studies have identified the PI3K signaling pathway as a key regulator in tumor biology and the immune microenvironment. This pathway enhances the activity of regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs), contributing to an immunosuppressive tumor microenvironment that impairs the effectiveness of cancer vaccines and immunotherapies. The present study explores PI3K isoforms, particularly p110γ and p110δ, and their associated signaling pathways. The therapeutic potential of selective PI3K inhibitors and their capacity to act synergistically with immunization strategies are analyzed. Targeting the PI3K signaling pathway represents a promising approach to counteract tumor-induced immune suppression and improve the efficacy of immune checkpoint inhibitors and vaccines, ultimately leading to better clinical outcomes. Full article

Background/Objectives: Crimean–Congo hemorrhagic fever virus (CCHFV) is an emerging, widely distributed zoonotic tick-borne pathogen. The virus causes severe disease in humans, and numerous wild and domestic animals act as reservoirs of it. Unfortunately, there are no effective therapies or safe vaccines commercialized nowadays for this particular virus. As CCHF (Crimean–Congo hemorrhagic fever) is a serious threat to public health, there is an urgent need to investigate the development of safe and effective vaccination strategies further. Methods: In this work, we have employed two immunization platforms based on protein nanoparticles and a modified vaccinia Ankara (MVA) viral vector using the nucleoprotein (NP) as the target antigen. The humoral and cellular immune responses were characterized by ELISA, ICS, and cytokine measurement. Results: This work shows that a single dose of the vaccine candidates was not as immunogenic as the heterologous vaccination using nanoparticles and MVA. A prime with NP nanoparticles (NS-NP) and a boost with MVA-expressing NP were capable of triggering significant levels of humoral and cellular immune responses against CCHFV in mice. Conclusions: Our study shows that the NS-NP/MVA-NP vaccination strategy effectively elicits a robust humoral and cellular immune response in a mouse model, emphasizing its potential as a protective approach against CCHFV lineages. Full article

Background/Objectives: Equine herpesvirus type-1 (EHV-1) enters through the upper respiratory tract (URT) and causes respiratory disease, abortions, and myeloencephalopathy in equids. Pre-existing immunity at the viral entry site, especially mucosal IgG4/7 antibodies, has recently been shown to correlate with protection from disease and incomplete viral replication at the URT. Here, we tested whether intramuscular (i.m.) vaccination with a commercial inactivated EHV-1/4 vaccine can induce mucosal antibodies (mucAbs) at the URT. Methods: Adult horses with complete EHV-1 vaccination and/or exposure histories were vaccinated i.m. six times within eight months. Before and after each vaccination, blood and nasal swab samples were obtained. Serum and mucAbs were measured in fluorescent bead-based EHV-1 assays. Results: All horses still had existing EHV-1 specific serum and mucAbs prior to vaccination, which were mainly composed of IgG4/7 antibody isotypes. Serum IgG4/7 significantly increased after the first vaccination and stayed high until the end of the study. An additional short-lasting serum IgG1 response was only induced by the first vaccine application. At the URT, mucAbs increased after five out of six i.m. vaccine injections. Like the systemic antibody response, mucAbs were dominated by IgG4/7 and a small IgG1 increase after the first vaccination. Conclusions: Our data emphasize that robust EHV-1 specific mucAb levels are obtained after i.m. vaccination with the inactivated EHV-1/4 vaccine used here. The findings have important implications for evaluating EHV-1/4 vaccines for their ability to induce and maintain protective mucosal IgG4/7 antibodies. Full article

Herpes simplex virus type 1 (HSV-1) is a very concerning pathogen due to its ability to persist in the host’s nervous system and continuously interfere with the immune system, which complicates treatment. Therefore, the development of an effective HSV-1 vaccine is crucial. In this study, we focused on an HSV-1 mutant strain, M6, which includes several deleted genes associated with viral infection virulence and latent infection function, and explored its infection of macrophages and immunological characteristics. The study found that both the attenuated strain M6 and the wild-type strain infect macrophages through the binding of the gD protein to the HVEM receptor on the macrophage surface. Compared to the wild-type strain, the attenuated M6 strain induced a milder immune response, characterized by the lower expression of immune signaling molecules and inflammatory cytokine levels. Upon reintroducing macrophages infected with the two strains into mice, the M6 strain induced lower levels of inflammatory cytokines and higher levels of chemokines in spleen cells and also slightly lower humoral and cellular immune responses than the wild-type strain. Further histopathological analysis revealed that mice in the attenuated M6 group showed more stable body weight changes and milder pathological damage in immune organs such as the liver, spleen, and lymph nodes. In conclusion, the attenuated M6 strain exhibits good immunogenicity and mild pathological side effects, suggesting its potential as an effective immunogen. Full article

Background: Few reports exist regarding the incidence and factors associated with allergic reactions to COVID-19 vaccines during post-marketing surveillance, especially for inactivated whole virus or viral vector vaccines. We aimed to determine the incidence and factors associated with self-reported allergic reactions to COVID-19 vaccines in the Thai population. Methods: A cross-sectional case-control study was conducted via telephone-based interviews. Cases were defined as physician-confirmed, self-reported vaccine recipients diagnosed with non-severe immediate allergic reactions, anaphylaxis, or delayed allergic reactions. Controls were randomly sampled from vaccinated individuals who reported no adverse events and were matched by the type of vaccine (1 case:2 controls). Demographic information and the history of atopic diseases were collected in both groups. Conditional logistic regression analysis was used to explore associated factors. Results: Among 215,079 vaccine doses administered, the incidence of self-reported skin symptoms of allergic reactions was 1821 events (0.85%). The risk factors for allergic reactions included age < 60 years (aOR 3.53; 95% CI:1.43–8.70; p = 0.006), female sex (aOR 8.33; 95% CI: 4.35–15.94; p < 0.001), a personal history of allergic rhinitis (aOR 4.32; 95% CI: 2.43–7.69; p < 0.001), atopic dermatitis (aOR 4.27; 95% CI: 1.74–10.47; p = 0.002), food allergies (aOR 6.53; 95% CI: 2.42–17.61; p < 0.001), and a family history of allergic disease (aOR 2.14; 95% CI: 1.12–4.08; p = 0.021). Conclusions: COVID-19 vaccines showed a low incidence of self-reported allergic reactions, which were more likely to occur in younger individuals, females, and those with a history of atopic diseases. Full article

Immunotherapy is becoming a promising strategy for treating diverse cancers. However, it benefits only a selected group of gastric cancer (GC) patients since they have highly heterogeneous immunosuppressive microenvironments. Thus, a more sophisticated immunological subclassification and characterization of GC patients is of great practical significance for mRNA vaccine therapy. This study aimed to find a new immunological subclassification for GC and further identify specific tumor antigens for mRNA vaccine development. First, deep autoencoder (AE)-based clustering was utilized to construct the immunological profile and to uncover four distinct immune subtypes of GC, labeled as Subtypes 1, 2, 3, and 4. Then, in silico prediction using machine learning methods was performed for accurate discrimination of new classifications with an average accuracy of 97.6%. Our results suggested significant clinicopathology, molecular, and immune differences across the four subtypes. Notably, Subtype 4 was characterized by poor prognosis, reduced tumor purity, and enhanced immune cell infiltration and activity; thus, tumor-specific antigens associated with Subtype 4 were identified, and a customized mRNA vaccine was developed using immunoinformatic tools. Finally, the influence of the tumor microenvironment (TME) on treatment efficacy was assessed, emphasizing that specific patients may benefit more from this therapeutic approach. Overall, our findings could help to provide new insights into improving the prognosis and immunotherapy of GC patients. Full article

Laryngeal papillomatosis and recurrent respiratory papillomatosis are caused by the human papillomavirus. It is characterized by papillomatous growths and is the most common benign disease of the larynx. Juvenile-onset RRP is characterized by more aggressive disease compared with adult-onset RRP. Patients often require frequent surgical procedures, with an increasing shift toward office-based treatment. A variety of surgical and adjuvant medical therapies are available with mixed responses. New targeted therapies and vaccines are currently under investigation as potential adjuncts in the management. Full article