Background: The emergence of coccidial drug resistance has intensified the search for sustainable, residue-free solutions to control poultry coccidiosis. This challenge has positioned plant essential oils as promising candidates among the priority research areas. The study aimed to investigate the efficacy of essential oils in improving immune function and intestinal health in white-feathered broilers challenged with a high-dose coccidial vaccine.
Methods: A total of 480 one-day-old broilers were randomly assigned to five treatments: uninfected (CON), infected (EC), infected + 500 g/t narasin (AT), and infected + 200 or 400 g/t essential oil blend (EOB200 or EOB400). There were 6 replicates per treatment and 16 broilers per replicate. All infected treatments received a 30-fold coccidial vaccine on d 14. The CON group was administered an equal volume of sterile normal saline on d 14 of the experiment. One bird per replicate was sampled on d 22, and the remainder were raised until d 42.
Results: Results showed that the challenge increased the fecal oocyst counts on d 21 and 28 and elevated intestinal lesion scores and serum interleukin-6 (IL-6) levels on d 21, while it decreased IL-10 levels on d 21 and reduced the villus height-to-crypt depth (V:C) ratio in the duodenum and jejunum (p < 0.05). Additionally, compared with the EC group, the AT, EOB200, and EOB400 groups reduced oocyst excretion and serum superoxide dismutase (SOD) (p < 0.05). The EOB200 group also showed the highest serum transforming growth factor-β (TGF-β) concentration, along with the lowest immunoglobulin G (IgG) level (p < 0.05). Moreover, within the infected groups, the EOB200 group exhibited the highest duodenal villus height and V:C ratio (p < 0.05).
Conclusions: These findings indicated that the EOB200 and EOB400 groups alleviated intestinal damage caused by the coccidial vaccine with an efficacy comparable to that of antibiotics, and the EOB200 group exhibited a superior effect. The results confirm that the essential oil blend holds great application potential as an alternative to antibiotics.
The development of a universal SARS-CoV-2 vaccine holds great promise for achieving broad and durable protection against existing and future coronavirus variants. The identification, selection, and rational redesign of conserved viral epitopes constitute the direct immunological foundation of universal SARS-CoV-2 vaccine development. The breadth and durability of protection are therefore primarily determined at the level of antigen and epitope design, whereas adjuvants, delivery platforms, and routes of administration serve as enabling and amplifying components rather than primary drivers of universality. Accordingly, this review discusses key determinants of universal vaccine design, including antigen selection, adjuvant utilization, and route of administration. The spike protein, particularly its receptor-binding domain, is a major antigenic target, but its high mutation rate challenges long-term vaccine efficacy. Strategies focusing on conserved epitopes in antigen designs show potential to elicit cross-neutralizing immune responses. Nanoparticle-based vaccines capable of presenting multiple homologous or heterologous antigens have demonstrated enhanced immunogenicity, broad protection in preclinical models and safety in clinical trials. The addition of next-generation adjuvants further amplifies humoral and cellular immunity beyond the capabilities of traditional aluminum-based adjuvants. Moreover, mucosal vaccine delivery may provide superior local protection at viral entry sites and limit transmission. Importantly, integrating these technological advances with epitope-centered antigen design and immunological data from vaccinated individuals will accelerate the identification of conserved epitopes and inform future vaccine design. A multidisciplinary approach combining optimized antigen engineering, novel adjuvant systems, and innovative delivery strategies is essential for the realization of a broadly protective universal SARS-CoV-2 vaccine.
Peptide-based vaccines offer a modular and readily manufacturable platform for both prophylactic and therapeutic immunization. However, their broader translation has been constrained by the limited capacity to predict protective immunity directly from sequence-level features. Recent advances in systems vaccinology and high-throughput immune profiling have substantially expanded the experimental evidence, while generative artificial intelligence now enables de novo design of peptide immunogens and multi-epitope antigens under precisely controlled constraints. This review approaches how these complementary developments are transforming peptide vaccine research, moving beyond classical reverse vaccinology and conventional epitope prediction toward integrated, data-driven design frameworks. We discuss key generative model architectures and conditioning strategies aligned with vaccine objectives, including approaches that account for structural presentation, antigen processing and population-level human leukocyte antigen (HLA) diversity. Central to this perspective is the requirement for rigorous experimental validation and for strengthening the computational-experimental feedback loop through iterative in vitro and in vivo testing informed by systems-level immune readouts. We highlight representative applications spanning infectious diseases, cancer immunotherapy and vector-borne vaccinology, and we outline major technical and translational challenges that must be addressed to enable robust real-world deployment. Finally, we propose future directions for precision peptide vaccinology, emphasizing standardized functional benchmarks, the development of richer curated datasets linking sequence space to immune outcomes, and the early incorporation of formulation and delivery constraints into generative design pipelines.
Background: People with HIV (PWH) face elevated risk of pneumococcal disease despite optimal antiretroviral therapy. In Italy, pneumococcal vaccination coverage in adults remains suboptimal. For PWH, access barriers may be amplified because adult vaccinations are primarily delivered in primary care, whereas HIV care is mostly hospital-based. Methods: We conducted a retrospective, observational study at an HIV clinic in Milan, Italy, evaluating the impact of an on-site vaccination service implemented in January 2019. At baseline, 1854 PWH were in active follow-up; 135 (7.3%) had previously received pneumococcal vaccination. We assessed vaccination uptake (PCV13-PPSV23 sequential schedule or PCV20) among the remaining 1719 unvaccinated individuals through December 2023. A logistic regression analysis was used to identify factors associated with vaccine acceptance. Results: Over five years, 745/1719 individuals (43.3%) either initiated PCV13 + PPSV23 or received PCV20, representing a six-fold increase from baseline. Of 639 individuals receiving PCV13, 80.1% completed the sequence with PPSV23. Most vaccinations (80.8%) were administered on-site. In multivariable analysis, men who have sex with men showed higher uptake (aOR 1.56, 95% CI 1.25-1.95), while regular and irregular immigrants had significantly lower uptake (aOR 0.70 and 0.24, respectively) compared to Italian nationals. Conclusions: Integration of vaccination services into routine HIV care substantially improved pneumococcal vaccination uptake. However, with nearly half of eligible patients remaining unvaccinated, additional strategies are required to address vaccine hesitancy and inequities, particularly among immigrants, to achieve optimal pneumococcal coverage in PWH.
Objectives: In response to the challenge that Staphylococcus aureus (S. aureus) vaccines fail to induce durable protective immunity, this study aims to develop a novel antigen-adjuvant co-design strategy. Specifically, we rationally combined the immunodominant toxin antigen LukS-PV with the immunologically subdominant adhesin antigen ClfA, co-delivered via the PLGA-PEG nanoadjuvant system, to elicit synergistic, durable, and balanced humoral and cellular immune responses.
Methods: Firstly, recombinant antigens LukS-PV and ClfA were individually covalently conjugated to PLGA-PEG 25% nanoparticles (25% NPs) using EDC/NHS chemical coupling to construct a combined nanovaccine, followed by systemic safety verification in a mouse model. Subsequently, specific antibody titers were detected by ELISA, and the secretion levels of IL-4, IFN-γ, and IL-17A were measured by ELISPOT assay to comprehensively evaluate the humoral and cellular immune responses induced by the vaccine. Finally, the protective efficacy of the vaccine was assessed through acute and long-term (up to 180 days) lethal challenge experiments, thereby verifying the effectiveness of this co-design strategy based on rational antigen selection.
Results: The combined vaccine group (25% NPs-rClfA + 25% NPs-rLukS-PV) not only elicited high levels of specific antibodies but, more importantly, induced robust cellular immune responses dominated by Th1 and Th17 cells. Challenge experiments confirmed that the protective efficacy of the combined vaccine was significantly superior to that of any single-antigen vaccine and provided complete protection for up to 180 days. Crucially, the same antigen combination formulated with a traditional aluminum adjuvant failed to confer this durable protection, underscoring the essential role of adjuvant synergy.
Conclusions: This study demonstrates that rational combination of immunodominant and subdominant antigens with a compatible nanoadjuvant induces synergistic and durable immunity against S. aureus. This co-design strategy addresses key limitations of previous vaccines and provides a promising foundation for future clinical development.
Background/objectives: Aged care residents are highly vulnerable to vaccine-preventable diseases. Despite recommendations and funding under Australian programs, vaccination rates among residents for COVID-19, influenza, pneumococcal and shingles remain sub-optimal. The aim of this work was to assess if tailored quality improvement interventions would improve vaccination coverage in aged care residents.
Methods: This was a quality improvement initiative evaluated using a quasi-experimental pre-post design. Building on previously identified barriers and enablers, a package of interventions and resources was developed to support consent processes, vaccination planning, and tracking. Pre- and post-intervention vaccination coverage was assessed using resident lists from participating aged care facilities and data extracted from the Australian Immunisation Register (AIR) at two time points, 14 months apart. A process evaluation survey was distributed to RACF staff.
Results: Of the 6964 residents listed, 5153 (74%) remained registered in AIR when data was extracted post-intervention. Shingles showed the greatest improvement in absolute difference (+23.4%), followed by pneumococcal (+14.2%) and influenza (+10.9%), despite a high baseline of 68.5%. COVID-19 coverage declined by 7.4% when applying a 6-month reporting interval. Twenty-five staff completed the process evaluation survey; 45% of respondents identified discrepancies between AIR data and internal records, indicating underreporting by external providers. Interventions including the consent template and vaccination tracker were reported as useful and were used to support local vaccination.
Conclusions: This quality improvement initiative improved coverage for three of the four recommended and funded vaccines for RACF residents and demonstrated the value of tailored interventions informed by consumer and provider feedback. The approach potentially offers a scalable model for improving vaccination rates in aged care across Australia.
Background: The prognosis of glioblastoma (GBM) patients remains poor. Dendritic cell (DC) vaccination has been investigated as an immunotherapy option, mainly in early-phase clinical studies. Herein, we report the feasibility, safety, and descriptive clinical and radiological outcomes of a retrospective series of newly diagnosed GBM patients treated with standard radio-chemotherapy and autologous DC vaccination as compassionate use.
Methods: We retrospectively reviewed the medical and radiological records of patients with newly diagnosed GBM who received autologous tumor lysate-pulsed DC vaccination in addition to standard-of-care treatment at a tertiary academic center between 2009 and 2017. Clinical data, treatment characteristics, adverse events, survival outcomes, and radiological responses were collected and analyzed descriptively.
Results: Twenty-four patients were included. All patients underwent surgical resection and were further treated with autologous tumor lysate-DC vaccination and standard radio-chemotherapy. Histology of GBM was confirmed in all patients. The first vaccine was administered in 75% of patients after a median of 21 days (range: 6-30 days) following surgery and prior to radiotherapy initiation. DC vaccination was continued following radiotherapy at specific time points, with no observed significant adverse events. Median OS was 21.1 months (95% CI, 27.9-75.0 months), and median PFS was 10.3 months (95% CI, 15.6-26.6 months). Presence of O6-methylguanine DNA methyltransferase (MGMT) promoter methylation was associated with longer survival and higher 12-month PFS rates, consistent with its established prognostic value. Radiological responses were retrospectively assessed according to RANO and RANO 2.0 criteria.
Conclusions: In this retrospective single-center series, autologous DC vaccination administered as compassionate use in combination with standard radio-chemotherapy was feasible and safe in routine clinical practice. Survival and radiological outcomes are reported descriptively and should be interpreted with caution given the absence of a control cohort. These findings support further prospective controlled studies to properly assess the clinical role of DC vaccination in newly diagnosed GBM.
Background: Highly potent vaccines are essential for the effective control of classical swine fever (CSF). Since CSF re-emerged in 2018 in Japan, the live CSF virus (CSFV) vaccine-a guinea pig exaltation of Newcastle disease virus-negative strain vaccine (GPE-, genotype 1.1)-has been applied to domestic pigs, contributing to a reduction in outbreaks. Meanwhile, the persistence and continued expansion of CSFV in wild boar populations have raised concerns regarding potential antigenic divergence. Methods: We systematically evaluated the neutralizing reactivity of sera from GPE--vaccinated pigs against CSFV strains (genotype 2.1) recently circulating in Japan against identified a representative strain that showed markedly reduced neutralization. We directly assessed the protective efficacy of the GPE- vaccine against this strain in a controlled challenge experiment. At 4 weeks post-vaccination, both vaccinated and unvaccinated pigs were orally challenged with the representative Japanese strain and monitored for 3 weeks thereafter. Results: Among the Japanese CSFV strains, the JPN/SM/WB/2022 isolate exhibited markedly reduced neutralizing reactivity-over 32-fold lower than that against the vaccine strain-when tested with GPE- vaccine-induced antisera. In the experimental infection in pigs, unvaccinated pigs exhibited typical clinical signs of CSF and viremia, and two pigs reached the humane endpoint. In contrast, none of the vaccinated pigs showed any clinical signs of infection. Robust humoral and cellular immune responses were induced in vaccinated pigs, which may correlate with the observed complete protection. Conclusions: The GPE- live vaccine provides protective immunity against an antigenically distinct strain, prevents disease, and limits viral spread in domestic pigs.
The prompt and extensive use of COVID-19 vaccines has dramatically reduced both cases and casualties, but it has also underscored a number of critical issues that need to be addressed for their full exploitation at global level. This Special Issue was launched to gather fresh data to improve the way we use vaccines that are currently available to contribute to the design and the development of new ones and to elucidate social, ethical and psychological concerns that might hamper vaccine acceptance and use. It includes 15 articles six of which address, under various aspects, the level and durability of protective immunity; five deal with the highly debated field of vaccine use, efficacy and safety, in persons with an impaired/dysregulated immune system; one paper reports on adjuvants' role in immune stimulation; one on the interference of natural adenovirus immunity with DNA vaccine response; one is a review on the cellular mechanisms of vaccine-dependent myocarditis; and one explores social attitudes to vaccines in different ethnic groups during early phases of the pandemic. Far from being complete and exhaustive, this Special Issue provides the reader with fresh insights into several critical questions raised by or connected to the advent of COVID-19 vaccines. This introductory article provides an overview of their contribution, while offering a quick glance at the current state of the art.
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