Search Results (284)

Background/Objective: Anti-tick vaccines represent a promising alternative to chemical acaricides for the management of ticks on wildlife; however, little progress has been made to produce a vaccine effective in wild hosts that are critical for tick reproduction, such as the white-tailed deer (Odocoileus virginianus). We recently tested Amblyomma americanum salivary and midgut extracellular vesicles as vaccine candidates in white-tailed deer, which resulted in on-host female tick mortality. The objective of this study was to identify the proteins recognized by the antibodies regenerated during these vaccinations to determine potential antigens for vaccine development for white-tailed deer. Methods: Using a proteomic approach, we characterized the cargo within salivary and midgut vesicles. Label-free quantitative proteomics were used to investigate significant changes in protein loading within extracellular vesicles in these two organs. The pre-vaccination and post-vaccination serum from three animals vaccinated with salivary and midgut vesicles and one control animal were used to identify proteins recognized by circulating antibodies. Results: We show that these salivary and midgut vesicles contain a “core-cargo” enriched in chaperones, small GTPases, and other proteins previously reported in small EVs. Label-free quantitative proteomics show significant differences in protein cargo between salivary and midgut vesicles (333 proteins out of 516). Proteomic analysis of immunoprecipitated proteins identified thirty antigens with potential for use in anti-tick vaccines, seven of which we have categorized as high priority. Conclusions: Proteins within tick salivary and midgut vesicles are recognized by antibodies from vaccinated white-tailed deer. These proteins can be further evaluated for their function and potential as vaccine candidates against ticks. Full article

This study selects the Inner Mongolia Autonomous Region (IMAR), among the most crucial beef-cattle farming areas in China, to obtain data from the micro-surveys of 447 beef-cattle farmers. Utilizing an endogenous switching regression (ESR) model, this research empirically investigates the effect of farmers’ beef-cattle insurance enrollment behavior on their input of disease prevention. This study finds that farmers adopting beef-cattle insurance reduce beef-cattle disease-prevention input. Based on counterfactual assumptions, if insured farmers had not adopted insurance, their input in disease prevention would increase by 33.45%. Further research confirms that a decrease in the market purchase price of beef cattle enhances the negative effect of farmers’ insured behavior on input for beef-cattle disease prevention. The heterogeneity analysis leads to two more conclusions. One is that insured farmers have the largest reduction in shed-disinfection input, the smallest reduction in voluntary vaccination input, and an intermediate reduction in deworming input. The other is that the act of adopting insurance reduces disease-prevention input to a greater extent for farmers who are far from the core areas of beef-cattle farming or who have not experienced beef-cattle deaths. Full article

Vaccination constitutes one of the most important means of preventing infectious disease in captive nonhuman primates (NHPs). Vaccination protocols for NHPs vary, as they are mostly guided by institutional preference, infection pressure, local availability, and recommendations by non-peer reviewed resources. Currently, no updated literature review about vaccination options for NHP is available. Therefore, we provide a detailed overview of published vaccination options for NHP. Our findings demonstrate that, while there are often insufficient scientific data to justify their use, the core vaccines used in most NHP species confer protection against tetanus, rabies, and measles. Where information is available, efficacy expectations, adverse effects, dosages and frequency of administration are provided. We advocate that the decision to vaccinate NHP for less common diseases, for which an off-label vaccine is available, should be grounded in a comprehensive risk assessment. This assessment should consider factors specific to the individual animal, the vaccine, the housing institution, the epidemiology of the disease, and relevant regulatory and ethical considerations. Full article

Hepatitis C virus (HCV) is a major public health concern, and the development of an effective HCV vaccine plays an important role in the effort to prevent new infections. Supramolecular co-assembly and co-presentation of the HCV envelope E1E2 heterodimer complex and core protein presents an attractive vaccine design strategy for achieving effective humoral and cellular immunity. With this objective, the two antigens were non-covalently assembled with an immunostimulant (TLR 7/8 agonist) into virus-mimicking polymer nanocomplexes (VMPNs) using a biodegradable synthetic polyphosphazene delivery vehicle. The resulting assemblies were characterized using dynamic light scattering and asymmetric flow field-flow fractionation methods and directly visualized in their vitrified state by cryogenic electron microscopy. The in vivo superiority of VMPNs over the individual components and an Alum-formulated vaccine manifests in higher neutralizing antibody titers, the promotion of a balanced IgG response, and the induction of a cellular immunity—CD4+ T cell responses to core proteins. The aqueous-based spontaneous co-assembly of antigens and immunopotentiating molecules enabled by a synthetic biodegradable carrier offers a simple and effective pathway to the development of polymer-based supramolecular nanovaccine systems. Full article

Despite the widespread use of COVID-19 vaccines, there is still a global need to find effective therapeutics to deal with the variants of SARS-CoV-2. Moslae herba (MH) is a herbal medicine credited with antiviral effects. This study aims to investigate the antiviral effects and the underlying mechanism of aqueous extract of Moslae herba (AEMH) for treating SARS-CoV-2. The in vitro anti-SARS-CoV-2 activity of AEMH was evaluated using cell viability and viral load. Component analysis was performed by HPLC-ESI-Q-TOF/MS. The connection between COVID-19 and AEMH was constructed by integrating network pharmacology and transcriptome profiles to seek the core targets. The components with antiviral activities were analyzed by molecular docking and in vitro pharmacological verification. AEMH exerted anti-SARS-CoV-2 effects by inhibiting viral replication and reducing cell death caused by infection (IC₅₀ is 170 μg/mL for omicron strain). A total of 27 components were identified from AEMH. Through matching 119 intersection targets of ‘disease and drug’ with 1082 differentially expressed genes of COVID-19 patients, nine genes were screened. Of the nine, the PNP and TPI1 were identified as core targets as AEMH treatment significantly regulated the mRNA expression level of the two genes on infected cells. Three components, caffeic acid, luteolin, and rosmarinic acid, displayed antiviral activities in verification. Molecular docking also demonstrated they could form stable bonds with the core targets. This study explored the antiviral activity and possible mechanism of AEMH for treating SARS-CoV-2, which could provide basic data and reference for the clinical application of MH. Full article

Brucellosis is a neglected zoonotic disease that has a significant economic and public health impact, especially in endemic countries. This review delves deeply into brucellosis’s current epidemiological situation and potential sources of livestock infection in Egypt during the last two decades. MLVA-16 and Whole Genome Sequencing based on core-genome SNP analyses confirm the presence of different B. abortus and B. melitensis outbreak strains, both older widely disseminated Brucella strains and newly introduced ones. Despite implementing the test-and-slaughter control strategy over forty years, the disease is still endemic, and different Brucella species circulate among several animal species. The raising of mixed animal species in the same households or farms, exposure to aborted animals, and lack of public awareness about brucellosis transmission are among the main risk factors for increasing livestock brucellosis prevalence in Egypt. Young animals’ voluntary vaccination, lack of a nationwide animal identification system, and uncontrolled animal movement stand beyond the ineffectively applied control strategy and may be subdued by applying mass vaccination to decrease disease prevalence dramatically and target imported camels, domestic pigs, and dogs (housed and stray) in the national control surveillance. Increasing awareness through educational campaigns is compulsory to reduce brucellosis transmission risk to livestock/humans. Full article

Background: Noroviruses, which cause epidemic acute gastroenteritis, and Plasmodium parasites, which lead to malaria, are two infectious pathogens that pose threats to public health. The protruding (P) domain of norovirus VP1 and the αTSR domain of the circumsporozoite protein (CSP) of Plasmodium sporozoite are the glycan receptor-binding domains of the two pathogens for host cell attachment, making them excellent targets for vaccine development. Modified norovirus P domains self-assemble into a 24-meric octahedral P nanoparticle (P₂₄ NP). Methods: We generated a unique P₂₄-αTSR NP by inserting the αTSR domain into a surface loop of the P domain. The P-αTSR fusion proteins were produced in the Escherichia coli expression system and the fusion protein self-assembled into the P₂₄-αTSR NP. Results: The formation of the P₂₄-αTSR NP was demonstrated through gel filtration, electron microscopy, and dynamic light scattering. A 3D structural model of the P₂₄-αTSR NP was constructed, using the known cryo-EM structure of the previously developed P₂₄ NP and P₂₄-VP8* NP as templates. Each P₂₄-αTSR NP consists of a P₂₄ NP core, with 24 surface-exposed αTSR domains that have retained their general conformations and binding function to heparan sulfate proteoglycans. The P₂₄-αTSR NP is immunogenic, eliciting strong antibody responses in mice toward both the norovirus P domain and the αTSR domain of Plasmodium CSP. Notably, sera from mice immunized with the P₂₄-αTSR NP bound strongly to Plasmodium sporozoites and blocked norovirus VLP attachment to their glycan receptors. Conclusion: These data suggest that the P₂₄-αTSR NP may serve as a combination vaccine against both norovirus and Plasmodium parasites. Full article

Extracellular vesicles (EVs) from Candida albicans can elicit immune responses, positioning them as promising acellular vaccine candidates. We characterized EVs from an avirulent C. albicans cell wall mutant (ecm33Δ) and evaluated their protective potential against invasive candidiasis. EVs from the yeast (YEVs) and hyphal (HEVs) forms of the SC5314 wild-type strain were also tested, yielding high survival rates with SC5314 YEV (91%) and ecm33 YEV immunization (64%). Surprisingly, HEV immunization showed a dual effect, resulting in 36% protection but also causing premature death in some mice. Proteomic analyses revealed distinct profiles among the top 100 proteins in the different EVs, which may explain these effects: a shared core of 50 immunogenic proteins such as Pgk1, Cdc19, and Fba1; unique, relevant immunogenic proteins in SC5314 YEVs; and proteins linked to pathogenesis, like Ece1 in SC5314 HEVs. Sera from SC5314 YEV-immunized mice showed the highest IgG2a titers and moderate IL-17, IFN-γ, and TNF-α levels, indicating the importance of both humoral and cellular responses for protection. These findings highlight the distinct immunogenic properties of C. albicans EVs, suggesting their potential in acellular vaccine development while emphasizing the need to carefully evaluate pathogenic risks associated with certain EVs. Full article

Background/Objectives: Rural communities in the United States experience increased disparity of care for both general healthcare services and access to routine vaccines. Previous research has indicated a 40% lower vaccination rate in rural communities, as compared to urban counterparts. Having a better understanding regarding factors influencing lower vaccination rates in rural areas could help public health officials prepare for future vaccination efforts. This research sought to gather and evaluate the opinions of people who live and work in rural areas regarding barriers to COVID-19 vaccine uptake. Methods: A semi-structured qualitative key informant interview design was utilized by researchers to gather opinions from university Extension staff in Washington State. Interview transcripts were analyzed using the Theory of Planned Behavior (ToPB) framework to evaluate COVID-19 vaccination-related intentions and motivational factors that the Extension staff observed among rural populations in their communities. Results: Twenty-one participants representing 34 out of the 40 Extension offices responded and were interviewed during fall 2023. Using the ToPB constructs, nine barriers were identified. Attitude-related barriers included the following: inherent social distancing in rural location negating vaccine necessity; lack of early vaccine availability in rural locales; concerns regarding ineffectiveness of the vaccine; and inadequate dissemination of vaccine information to non-English language speakers and those with limited access to technology. Subjective norm barriers included the following: perception of exclusion of rural populations’ unique needs during design and implementation of vaccine mandates; exertion of social pressures on rural individuals’ vaccine uptake decision; and highly visible breakdown in standard trust in core community institutions and leadership. Barriers related to loss of perceived behavioral control included vaccine mandates impacting self-perceived loss of autonomy and limitations in vaccine technology information impacting perception of vaccine safety. Conclusions: By identifying barriers to vaccination in rural communities during the COVID-19 pandemic, future outreach efforts can be designed to improve intention and lead to stronger vaccination uptake. Full article

Background: Echinococcosis is a zoonotic infectious disease that poses a significant threat to the health of individuals living in rural regions. While vaccination represents a potential strategy for disease prevention, there is currently no effective vaccine available for humans to prevent cystic echinococcosis (CE). This study aimed to design a novel multi-epitope vaccine (MEV) against Echinococcus granulosus for human use, employing immunoinformatics methods. Methods: We identified core epitopes from two key antigens, EgA31 and EgG1Y162, and integrated them into the immunoglobulin variable region of CTLA-4 (CTLA-4lgV) to create the CVE31-162 vaccine construct. The secondary and tertiary structures of the CVE31-162 were established using bioinformatics methods. The interaction between the CVE31-162 and B7 molecules was assessed through molecular dynamics simulations. Finally, both in vitro and in vivo experiments were conducted to validate the effectiveness of the CVE31-162 against the immunological effects of Echinococcus granulosus. Results: Bioinformatics analysis indicated that CVE31-162 exhibits favorable antigenicity, stability, and non-allergenicity. Furthermore, CVE31-162 demonstrated a stable three-dimensional structural model. Molecular docking (MD) and molecular dynamics simulations (MDS) revealed a strong binding affinity between CVE31-162 and B7 molecules. Immune simulation results suggested that the vaccine elicits robust humoral and cell-mediated immune responses. Both in vitro and in vivo experiments demonstrated that immunized mice exhibited significantly elevated levels of antigen-specific antibodies and enhanced lymphocyte proliferation compared to the control group. Conclusions: CVE31-162, which is based on the interaction between CTLA-4 and B7, represents a promising multi-epitope vaccine for Echinococcus granulosus. Full article

Background/Objectives: A “people-centered” approach is one of the core principles of the Immunization Agenda (IA) 2030 and emphasizes the need for services to be organized around the needs and expectations of individuals and the community. A better understanding of the immunization experience from the client’s perspective is key to guiding the design of policies and interventions aimed at improving immunization delivery and coverage. This study provides a synthesis of the immunization experiences of children’s caregivers in Cameroon, highlighting potential barriers for timely and complete immunization. Methods: A descriptive cross-sectional study was conducted, targeting caregivers of children brought to selected health facilities for immunization in all ten regions of Cameroon. Using structured questionnaires, data were collected from caregivers and analyzed using STATA version 13. Results: In total, 1230 caregivers were interviewed in 265 health facilities. The median age of participants was 27 years and the median number of children per caregiver was two children. Most (87%) of the study participants reported to be satisfied with immunization service delivery. The median waiting time for vaccination was 1 h 48 min, with regional median waiting times ranging from 18 min in the South region to 4 h 6 min in the North region. About a quarter (24%) of surveyed participants reported to have presented to a health facility for immunization services and were turned away without achieving the purpose for which they came at least once. About half (48%) of the caregivers had never heard about planned vaccination activities in their communities. Conclusion: While most caregivers appeared to be satisfied with immunization service delivery in Cameroon, our study highlights some notable caregiver concerns (long waiting times, unproductive immunization visits and inadequate information about outreach activities) which, if addressed, may go a long way to enhance the immunization experience of caregivers in Cameroon, build trust in immunization services and thus improve vaccination uptake. Full article

Background/Objectives: Poxviruses are large DNA viruses that replicate in the host cytoplasm without a nuclear phase. As vaccine vectors, they can package and express large recombinant cassettes from different positions of their genomic core region. We present a comparison between wildtype modified vaccinia Ankara (MVA) and isolate CR19, which has significantly expanded inverted terminal repeats (ITRs). With this expansion, a site in wildtype MVA, called deletion site (DS) IV, has been duplicated at both ends of the genome and now occupies an almost central position in the newly formed ITRs. Methods: We inserted various reporter genes into this site and found that the ITRs can be used for transgene expression. However, ITRs are genomic structures that can rapidly adapt to selective pressure through transient duplication and contraction. To test the potential utility of insertions into viral telomers, we inserted a factor from the cellular innate immune system that interferes with viral replication as an example of a difficult transgene. Results: A site almost in the centre of the ITRs can be used for transgene expression, and both sides are mirrored into identical copies. The example of a challenging transgene, tetherin, proved to be surprisingly efficient in selecting candidate vectors against the large background of parental viruses. Conclusions: Insertion of transgenes into ITRs automatically doubles the gene doses. The functionalisation of viruses with tetherin may accelerate the identification and generation of recombinant vectors for personalised medicine and pandemic preparedness. Full article

Background: Pediatric hepatitis B virus (HBV) serostatus remains variably characterized, hardly determined at times, or documented as part of national monitoring of the Extended Programs for Immunization (EPI). Methods: We cross-sectionally characterized the seroprevalence of HBV vaccine and/or infection status among 501 and 288 children <5 and 15–17 years old, respectively, in Kawempe Division, Kampala, Uganda, between May and August 2023. These children received HBV vaccination under the Uganda National Extended Program on Immunizations (UNEPI). Samples were qualitatively screened for hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (HBsAb or anti-HBs), hepatitis B e antigen (HBeAg), hepatitis B e antibody (HBeAb or anti-HBe), and for hepatitis B core antibody (HBcAb or anti-HBc) using three different HBV Combo test rapid immunochromatographic diagnostic tests: Nova, Fastep, and Beright. Results: The seroprevalence of HBsAg, anti-HBs, HBeAg, anti-HBe, and anti-HBc was 1.52%, 27.75%, 0.88%, 0.63%, and 0.76%, respectively, for the combined study age groups. The HBsAg seroprevalence of 2.78% was almost 3.5-fold higher among adolescents when compared to the 0.8% observed in the under-5-year-olds. The qualitative seroprevalence of anti-HBs was 33.1% and 18.4% in the under-5 and among the 15–17-year-old study groups, respectively. Conclusions: The proportion of qualitatively detectable anti-HBs in both groups of vaccinated children is low and probably indicates reduced seroprotection. Consequently, a large proportion of children who received the hepatitis B vaccine under UNEPI may be at risk of HBV infection, especially adolescents. A booster dose of the Hepatitis B Vaccine may be required for adolescents. Full article

The etiology of autism spectrum disorder (ASD) has not yet been completely elucidated. Through time, multiple attempts have been made to uncover the causes of ASD. Different theories have been proposed, such as being caused by alterations in the gut–brain axis with an emphasis on gut dysbiosis, post-vaccine complications, and genetic or even autoimmune causes. In this review, we present data covering the main streams that focus on ASD etiology. Data collection occurred in many countries covering ethnically diverse subjects. Moreover, we aimed to show how the progress in genetic techniques influences the explanation of medical White Papers in the ASD area. There is no single evidence-based pathway that results in symptoms of ASD. Patient management has constantly only been symptomatic, and there is no ASD screening apart from symptom-based diagnosis and parent-mediated interventions. Multigene sequencing or epigenetic alterations hold promise in solving the disjointed molecular puzzle. Further research is needed, especially in the field of biogenetics and metabolomic aspects, because young children constitute the patient group most affected by ASD. In summary, to date, molecular research has confirmed multigene dysfunction as the causative factor of ASD, the multigene model with metabolomic influence would explain the heterogeneity in ASD, and it is proposed that ion channel dysfunction could play a core role in ASD pathogenesis. Full article

Klebsiella pneumoniae is well recognized as a serious cause of infection in healthcare-associated settings and immunocompromised individuals; however, accumulating evidence from resource-limited nations documents an alarming rise in community-acquired K. pneumoniae infections, manifesting as bacteremia and pneumonia as well as neonatal sepsis. The emergence of hypervirulent and antibiotic-resistant K. pneumoniae strains threatens treatment options for clinicians. Effective vaccination strategies could represent a viable alternative that would both preempt the need for antibiotics to treat K. pneumoniae infections and reduce the burden of K. pneumoniae disease globally. There are currently no approved K. pneumoniae vaccines. We review the evidence for K. pneumoniae lipopolysaccharide (LPS) as a vaccine and immunotherapeutic target and discuss the role of antibodies specific for the core or O-antigen determinants within LPS in protection against Klebsiella spp. disease. We expand on the known role of the Klebsiella spp. capsule and O-antigen modifications in antibody surface accessibility to LPS as well as the in vitro and in vivo effector functions reported for LPS-specific antibodies. We summarize key hypotheses stemming from these studies, review the role of humoral immunity against K. pneumoniae O-antigen for protection, and identify areas requiring further research. Full article