Search Results (2,376)

Mycobacterial diseases, including tuberculosis (TB), remain the major health and economic challenges in livestock, underscoring the need to characterise the innate immune mechanisms involved in early bacterial containment. Alveolar macrophages (AMs) are the first line of defence against inhaled mycobacteria, yet the functional links between activation, polarisation, and phagocytic capacity in caprine AMs remain poorly defined. In this study, we compared a pH-dependent live-cell fluorescence assay with a culture-based method to evaluate phagocytosis and clearance of Mycobacterium fortuitum under different immunostimulatory conditions. AMs were stimulated in vitro with LPS or Heat-inactivated Mycobacterium bovis (HIMB), and phagocytosis was assessed alongside activation and pro-inflammatory markers. Both approaches showed that LPS stimulation significantly enhanced mycobacterial clearance, despite reduced initial bacterial uptake. Moreover, this improved phagocytic capacity was associated with increased expression of the inducible Nitric Oxide Synthase (iNOS), MHCII, CD80, and CD86, as well as an elevated production of some pro-inflammatory cytokines. In contrast, HIMB induced cytokine secretion but failed to enhance activation markers or bacterial clearance. Collectively, these results establish the first association between pro-inflammatory activation and functional mycobacterial phagocytosis in caprine AMs and validate a robust methodological framework for studying innate immune responses relevant to TB and vaccine development in goats. Full article

Introduction: Cholera remains a major public health threat in endemic settings, and oral cholera vaccine (Shanchol™) campaigns are increasingly used amid constrained global supply. However, practical decisions on revaccination require clearer, setting-specific estimates of how rapidly vaccine-induced vibriocidal antibodies peak and wane. Methods: We conducted a prospective cohort kinetics analysis in Lukanga Swamps (Central Province, Zambia), enrolling adults (18–65 years) stratified by prior Shanchol™ exposure (0, 1, or 2 previous doses). All participants received two Shanchol™ doses 14 days apart, with serum collected at baseline and days 14, 28, 60, and 90 (end of follow-up). Ogawa and Inaba vibriocidal titres were measured using a complement-based assay and analysed on the log10 scale. Serotype-specific mixed-effects models with natural cubic splines for time (knots: 14, 28, 60 days) assessed trajectories by prior-dose strata, adjusting for age, sex, and HIV status. Peak timing and post-peak half-life were derived from model-based predictions with participant-level bootstrap CIs (1000 replications). Results: The analysis included 225 participants: 68 (30.2%) with zero prior doses, 89 (39.6%) with one, and 68 (30.2%) with two; median age was 33 years (IQR 25–49), 56.4% were female, and 19.2% were HIV-positive. Modelled titres for both serotypes rose steeply after vaccination, peaking around day 36–37 across prior-dose strata. Ogawa titres reached half of peak by about day 73–78, corresponding to post-peak half-lives of 37–41 days; Inaba declined more slowly with half-lives of 42–46 days. Confidence intervals overlapped across prior-dose strata, indicating minimal differences by vaccination history. Conclusions: In this cholera-endemic adult population, Shanchol™ induced vibriocidal responses that peaked at ~5 weeks and waned over the following 5–7 weeks, with broadly similar kinetics regardless of prior vaccination and slightly slower decay for Inaba than Ogawa. These parameters can inform booster timing in hotspot settings. Full article

Objectives: To analyze the changes in the proportion of the rotavirus vaccine among children born in the 2017–2023 cohort and to assess the current status of rotavirus vaccination coverage in Suzhou, China. To monitor adverse events following immunization (AEFIs) so as to provide data for scientific guidance regarding the rotavirus vaccine. Methods: The basic information of children born between 1 January 2017 and 31 December 2023 in Suzhou and information regarding rotavirus vaccination were collected through the child module of Jiangsu Province Vaccination Integrated Service Management Information System. Information on AEFI case reports was collected from the AEFI monitoring system of the China Information System for Disease Control and Prevention. Descriptive epidemiological methods were used to analyze the rotavirus vaccine characteristics and AEFI classification, and the Mann–Whitney U test was used for comparative analysis. Results: The proportion of children born in the 2017–2023 cohort who received the first dose of the rotavirus vaccine was 14.65%. The reassortant rotavirus vaccine, live, oral, pentavalent (RV5) proportion gradually increased, and the vaccine proportion of children in the 2023 birth cohort reached the highest. The peak age for rotavirus vaccination was between 2 and 8 months. A total of 49,507 children (99.88%) received the first dose of RV5 at the age of 6–12 weeks in this birth cohort, and there was a statistically significant difference in the median duration of the first dose of RV5 among children of different age groups (p < 0.001). A total of 89 cases of AEFIs were reported, and the reported incidence of AEFIs was 3.47/10,000 doses. Among them, 86 cases of general reactions were reported, with a reported incidence of 3.35/10,000 doses, and three cases of abnormal reactions were reported, with a reported incidence of 0.12/10,000 doses. Conclusions: The rotavirus vaccine proportion of children born in Suzhou from 2017 to 2023 was not high. The incidence of AEFI reports from the rotavirus vaccine is relatively low, indicating a favorable safety profile. Efforts should prioritize strengthening health education on rotavirus gastroenteritis to enhance public confidence in vaccination, thereby ensuring the effective prevention and control of rotavirus gastroenteritis. Full article

In 2022, Australia saw an unprecedented outbreak of Japanese encephalitis virus genotype IV (JEV GIV). The outbreak involved 42 human cases with 7 fatalities, as well as affecting >80 pig farms in New South Wales and Queensland. Herein, we designed, constructed, and tested two JEV GIV mRNA vaccines encoding prME, which provided protection against a lethal JEV GIV challenge in an Ifnar-/- mouse model. The vaccines were not codon optimized and included either the Native (full-length) or a Shorter signal peptide, with the latter missing the N-terminal n-region. Two vaccinations with 5 µg of the Shorter vaccine provided neutralizing antibody responses that were significantly lower but overlapped with those seen after vaccination with Imojev, a live attenuated vaccine approved for use in humans. Both mRNA vaccines provided approximately a five to six log reduction in viremia, ≥80% protection against overt disease and weight loss, and mortality. The paper illustrates in-country mRNA vaccine generation in response to a local outbreak, with JEV mRNA vaccines potentially emerging to be easier to manufacture, cheaper, and more suitable for immunocompromised individuals. Full article

Background/Objectives: Acne vulgaris is a chronic inflammatory skin disorder characterized by sebaceous gland hyperactivity, follicular hyperkeratinization, proliferation of Cutibacterium acnes (C. acnes), and subsequent inflammation. The development of effective therapeutics necessitates reliable preclinical models that accurately replicate key pathological aspects of the human disease. Methods: In this study, we established an inflammatory acne model in Wistar rats via the intradermal injection of live C. acnes into the ear pinnae and thoroughly characterized its temporal dynamics of the induced inflammation. Utilizing this model, we evaluated the protective efficacy of a whole-cell inactivated C. acnes vaccine (HI-C. acnes) formulated with adjuvants WS03 or MA107b. Results: Inflammation peaked between days 1 and 3 post-infection, manifesting as pronounced erythema, ear swelling, increased ear thickness, elevated bacterial load, and significant upregulation of pro-inflammatory cytokines (IL-6, IL-1β, and MCP-1). Histopathological examination revealed extensive neutrophil infiltration and microabscess formation, while immunohistochemistry confirmed localized overexpression of TNF-α, IL-1β, and CXCL1 within the lesional tissue. Inflammatory manifestations gradually subsided by day 5 and were fully resolved by day 7, which coincided with complete bacteria clearance and normalization of pro-inflammatory cytokine levels. Vaccinated rats developed significantly higher C. acnes-specific IgG titers and, upon challenge, exhibited markedly reduced ear swelling, diminished bacterial burden, and suppressed expression of key inflammatory mediators compared to control groups, indicating that vaccine-induced protection is associated with humoral immunity. Conclusions: Collectively, our standardized and quantifiable rat ear inflammation model provides a robust platform for mechanistic investigations and preclinical assessment of novel anti-acne vaccines and therapeutic agents. Full article

Background: A novel platform to produce whole-virion vaccines using riboflavin and ultraviolet (UV) light for photochemical inactivation has been developed. We previously reported on the potential for this platform to produce a safe and effective inactivated whole-virion SARS-CoV-2 vaccine. Feasibility studies used a hamster infection challenge model to explore the effects of route of administration and adjuvants on immune responses elicited by the vaccine candidate. Here, we utilized the same animal model to evaluate the dose response to the vaccine candidate in combination with the adjuvant CpG1018. Methods: A pilot batch of the vaccine candidate was produced at a contract development and manufacturing organization (CDMO) for use in this study. A two-dose intramuscular regimen at three antigen concentrations formulated with CpG1018 adjuvant was assessed against a live SARS-CoV-2 (USA-WA-1/2020) challenge. Results: The vaccine elicited dose-dependent neutralizing antibody responses, with peak PRNT₅₀ titers exceeding 1:5120. Vaccination significantly reduced lung viral burden and mitigated pulmonary pathology compared to controls. Antibodies persisted up to 154 days post-vaccination and neutralized Delta and Omicron (Jn.1) variants but showed limited activity against XBB.1.5. Flow cytometry revealed enhanced CD4⁺ Th1-biased responses in higher-dose groups. Conclusions: These findings demonstrate the protective efficacy of the SolaVAX SARS-CoV-2 vaccine candidate and support further evaluation of this vaccine production platform. Full article

Background: Vaccines save lives, but only if they are available at health facilities for administration. Stockouts occur for various reasons, including inaccurate forecasting and resupply calculations. Population-based forecasts are typically used for immunization programs, yet they are often based on inaccurate population estimates. This retrospective study analyzed available routine facility-level data from two districts in Mozambique to provide insights for improved supply chain management, including resupply decisions, at the facility level. Methodology: Data from August to October 2023 were collected and analyzed for wastage rate, session cohort, and forecast accuracy. Results: The results show that district-level wastage rates are nominally different from globally acceptable standards, while being significantly different at the facility level. Analysis also showed divergence of vaccination doses provided to a session cohort during the month-long periods that appear to be correlated with periods of stockout. Using population-based forecasting for resupply methodology consistently undersupplied facilities by 20% (ranging from 5 to 41% across 16 facilities), while using the number of doses of administered BCG as a proxy for the population oversupplied by 12% (ranging from 1% underforecast and 28% overforecast), with tighter variance. Conclusions: Despite limitations due to the availability and quality of data, the results suggest an opportunity to shift from a traditional population-based approach to forecasting and resupply decisions, leveraging existing data systems, applying tailored wastage rates, and adjusting inventory management policies to ensure vaccine availability. Full article

Monkeypox virus (MPXV) is a zoonotic Orthopoxvirus responsible for Monkeypox (Mpox), historically associated with sporadic zoonotic transmission but increasingly characterised by sustained human-to-human spread. While vaccinia-based vaccination is known to confer cross-protection against MPXV, the durability of such immunity over a human lifetime remains incompletely characterised. Here, we assessed humoral and cellular immune responses to MPXV in octogenarians and nonagenarians vaccinated against smallpox during childhood. Twenty-three adults aged 79–94 years (median 83), who self-reported childhood vaccinia vaccination between 1925 and 1940, were recruited. MPXV-specific antibody responses were evaluated using ELISA, targeting homologous vaccinia and MPXV proteins, and live-virus neutralisation assays. Cellular immunity was assessed by IFN-γ ELISpot following stimulation with peptide pools derived from highly conserved vaccinia antigens. Responses were also obtained from younger, recently MVA–BN-vaccinated and unvaccinated control donors. All historically vaccinated participants exhibited MPXV-reactive IgG responses, with antibody binding and neutralisation levels comparable to recently vaccinated individuals. Functional neutralising activity against MPXV was detected in all donors, with ≥50% neutralisation observed in 78% of participants. Antibody concentrations correlated strongly with neutralisation capacity. T-cell responses were detectable in all historically vaccinated donors, most prominently against the major core protein A10L, although reduced magnitudes were observed in participants over 90 years of age. No MPXV-specific humoral or cellular responses were detected in unvaccinated controls. These findings demonstrate that childhood vaccinia vaccination induces durable humoral and cellular immunity against MPXV persisting for over seven decades. Historical smallpox vaccination status may therefore remain a relevant determinant of protection against Mpox. Full article

People living with HIV-1 (PLWH) are part of the so-called “fragile” populations to which COVID-19 vaccines were/are strongly recommended. The fact that most widely used COVID-19 vaccines rely on the production of a biologically active SARS-CoV-2 Spike protein expressed by synthetic mRNA poses the relevant question of whether and how this vaccination influences the fate of the HIV-1 reservoir. This report presents a detailed analysis of the literature data on the effects of SARS-CoV-2 Spike and COVID-19 vaccines on HIV-1 latently infected cells. Despite being limited in number, the experimental evidences consistently indicate that vaccine mRNA and/or SARS-CoV-2 Spike can effectively reactivate latent HIV-1. This conclusion has been drawn after “in vitro”, “ex vivo”, and “in vivo” assays, and with virus-associated Spike, soluble Spike, or its intracellular expression, as well as with COVID-19 mRNA vaccines. On the other hand, real-world observations on vaccinated PLWH under antiretroviral therapy (ART) provided evidence of HIV-1 reactivation almost exclusively in PLWH with unsuppressed viremia, as measured in terms of size of the HIV-1 reservoir. Although several issues still need to be clarified through urgent additional investigations, these data suggest the possibility that the Spike protein and/or the vaccine mRNA molecules affect the HIV-1 latency in PLWH. Full article

Porcine epidemic diarrhea virus (PEDV) has emerged as a major pathogen responsible for porcine diarrheal diseases, causing outbreaks of severe diarrhea and high mortality in neonatal piglets, thereby inflicting severe economic losses on the global swine industry. Current commercial PED vaccines, comprising conventional inactivated and live attenuated formulations, have exhibited progressively diminished efficacy in the face of emerging PEDV variants. The development of high-efficiency vaccine platforms is therefore critical for PED control. This study engineered a cellular membrane nanovesicle (CMN)-based vaccine, which differs from existing inactivated or subunit vaccines by presenting the PEDV spike (S) protein on the cell membranes to mimic the bilayer phospholipid structure of the viral envelope. The full-length S protein (FS, aa 19-1309) or a truncated S protein fragment (TS, aa 19-726) was expressed in Expi293F cells, followed by extraction of cell membranes to assemble antigen-displaying CMN vaccines. Compared with commercial live attenuated vaccine, administration of the CMN vaccine elicited high-titer neutralizing antibodies and elevated IFN-γ-producing CD8⁺ T cells in murine studies. Safety assessments revealed no adverse effects on body weight, hepatic/renal function indices, or histopathological parameters in vaccinated mice. Furthermore, immunization of piglets elicited notable humoral and CD8⁺ T cell immune responses. Collectively, the strategy of CMN-based vaccine described herein delivers a potential PEDV vaccine platform, thereby offering a novel avenue for next-generation veterinary vaccine development. Full article

Background/Objectives: An attenuated strain of Micropterus salmoides rhabdovirus (MSRV) 0509 with good immunogenicity has been isolated, showing potential as a candidate for live vaccine development. Methods: To improve the shelf life of attenuated strain of MSRV0509, the virus was formulated using three distinct single-protectant formulations and twelve thermostable protective agent formulations (designated T1–T12). Following lyophilization, the thermostability of each formulation was evaluated. Results: Results indicated that formulations T1, T9, and T10 maintained stable viral titers after storage at 25 °C and 37 °C. Moreover, these formulations retained high viral viability after 12 months at 4 °C, with a titer reduction of less than 0.5 log₁₀. Immunological analyses revealed that the freeze-dried MSRV vaccine elicited both humoral and immune factors responses in largemouth bass. Immersion immunization provided effective protection, yielding a survival rate exceeding 80%. Freeze-dried vaccines maintained their immunogenicity (i.e., the ability to induce antibodies) following 12 months of storage at 4 °C. Additionally, expression of IFN-γ and IL-12 was significantly upregulated in fish post-vaccination. Conclusions: In conclusion, the lyophilized MSRV vaccine developed in this study not only exhibits improved thermostability and extended shelf life, but also effectively preserves its immunogenic properties, supporting its potential for practical aquaculture applications. Full article

Global cancer incidence reached 20 million new cases across 185 countries in 2022, with approximately 10 million cancer-related deaths annually. Among adults with solid tumors and hematological malignancies, infections are a major contributor to morbidity and mortality, with respiratory infections playing a particularly significant role. These infections not only reduce life expectancy but can also delay cancer therapy, negatively affect treatment outcomes, and increase healthcare costs. In recent years, the burden of respiratory infections in this population has been driven by influenza virus, SARS-CoV-2, respiratory syncytial virus, Streptococcus pneumoniae, and Bordetella pertussis. Effective vaccines are available for all these pathogens and are recommended for adults with cancer, yet vaccination uptake remains suboptimal despite their heightened vulnerability. This review provides practical guidance for healthcare professionals on vaccinating adults with cancer against respiratory infections, summarizing key information to help clinicians address vaccination-related complacency, confidence, and convenience. Evidence from studies in both the general population and cancer patients consistently shows that vaccination benefits outweigh potential risks, with adverse event rates comparable to those seen in individuals without cancer. Early vaccination is encouraged, as there is limited justification for delaying immunization even when immune responses may be reduced. Vaccine dosing aligns with recommendations for the general population, with important exceptions. Live attenuated vaccines should be avoided because of the risk of replication and disease in immunocompromised patients, and selected groups may require booster doses to achieve adequate protection. Notably, cancer immunotherapy does not appear to impair vaccine-induced immune responses. Full article

One of the challenges post-COVID-19 is reducing the negative impacts on quality of life, performance, and independence in activities of daily living. Assessing functional dependence in adults one year after acute infection can help to understand the long-term consequences, evaluate the impact on quality of life, plan rehabilitation and healthcare, identify the most vulnerable groups, measure the socioeconomic impact, and support public policies and clinical decisions. Objectives: The objectives of this study are as follows: (a) to assess the prevalence of functional dependence in Brazilian adults with COVID-19; (b) to analyze the association between the study variables; and (c) to determine the factors associated with functional dependence. Methods: This was an observational, cross-sectional study with 987 adults (18 to 59 years old) living in the State of Paraná (Brazil) hospitalized for COVID-19 between March and December 2020. Data were collected by telephone 12 months after the acute infection using an instrument to retrieve sociodemographic and health information, and a functional dependence scale to assess dependence before COVID-19 retrospectively (using participant recall information) and at the time of the interview. Data were analyzed using penalized logistic regression after imputing missing data. Data were analyzed using penalized logistic regression after imputing missing data. Results: Functional dependence after COVID-19 was 5.0% and was associated with low levels of education, not having a partner, living with someone, not owning a home, experiencing job changes, requiring care, obesity, smoking, multimorbidity, ICU admission in the acute phase, use of invasive ventilation, or having Long COVID. Individuals who required care or used invasive ventilation support were, respectively, 9.3 and 6.5 times more likely to develop dependence after COVID-19. Despite adjustment for multiple factors, the magnitude of the observed effects warrants cautious interpretation, as unmeasured or residual confounding effects may still be present. Sample recall bias due to collection after 12 months and the presence of the alpha variant without COVID-19 vaccination coverage may limit data generalization. Conclusions: The results highlight the need to emphasize the public health implications of identifying functional dependence. In this vein, it is necessary to implement preventive measures, identify and monitor more vulnerable groups, plan rehabilitation programs, and develop public health policies. Full article

The reasons for disease outbreaks caused by Actinobacillus pleuropneumoniae (APP) in vaccinated pigs are often unknown and remain a challenge for farmers and veterinarians. One hypothesis for APP vaccine failure is the timing of APP vaccination during field or vaccine-induced viremia with Porcine Reproductive and Respiratory Syndrome Virus (PRRSV), which may negatively affect the immune response to APP vaccination. In this study, fattening pigs were vaccinated with a modified live vaccine (MLV) against PRRSV either at the beginning of the fattening period (group G1) or six weeks later (group G2). All pigs were vaccinated against APP five days after the start of fattening, which coincided with MLV-PRRSV viremia in G1. Within both G1 and G2, four subgroups of pigs (n = 10) were vaccinated with three different APP vaccines or remained unvaccinated to assess serological responses to various APP antigens. MLV-PRRSV viremia had no significant effect on APP-ApxII (p = 0.127), APP-LPS (p = 0.120), or opsonophagocytic antibody responses on day 40 of fattening. Lung lesion scores at slaughter were significantly higher (p = 0.004) in pigs from G2 (1.82 ± 2.38) compared with those from G1 (0.65 ± 0.88). All APP vaccines elicited presumably protective opsonophagocytic antibodies. In conclusion, no effects of MLV-PRRSV viremia on serological responses following APP vaccination were observed. Full article

Rabies is a neglected tropical zoonotic disease caused by rabies-virus (RV) infection and is responsible for almost 60,000 annual deaths globally, largely affecting the socio-economically disadvantaged population. Although fatality is preventable by immunization either before or after exposure with therapeutic antibodies, the high cost of prophylaxis or treatment limits their accessibility for the affected population. However, due to the almost 100% fatality rate in symptomatic individuals, almost 29 million annual vaccinations are performed, imposing high financial burden. Human transmission occurs principally through bites from infected dogs and although multiple mammalian species are permissive to RV, transmission from them or from symptomatic humans is rare. To overcome the limitations posed by the requirement of biosafety level-3 (BSL-3) containment for live virus culture, we established a replication-deficient vesicular stomatitis virus (VSV) pseudovirus expressing the Rabies-G (RV-G) protein and a multiplexed Luminex immunoassay for quantifying anti-rabies antibodies in equine sera. The purified pseudovirus exhibited robust luciferase activity and was able to infect multiple mammalian cell lines, although with variable efficiency. Using hyper-immunized equine serum, we observed a strong correlation (ρ > 0.9, p < 0.001) between binding antibody titers measured by the Luminex assay with neutralizing antibody titers determined using the pseudovirus-based neutralization assay. These assays provide a safe, quantitative, and BSL-2-compatible platform for rabies serological evaluation and vaccine testing. Full article