Vaccines最新文献

Background: Non-typhoidal Salmonella (NTS) is a major foodborne pathogen, with poultry products, especially eggs, being the primary source of human infections. Current serovar-specific poultry vaccines effectively reduce targeted Salmonella serovars but may inadvertently promote the emergence of untargeted serovars within poultry flocks. Therefore, novel vaccine candidates providing broad cross-serovar protection are needed to improve overall effectiveness of Salmonella control programs. Objectives: This study evaluated the immunogenicity of the novel subunit vaccine candidate InvG and assessed its ability to reduce Salmonella colonization in vaccinated laying hens and their progeny through maternally derived antibodies transferred via egg yolk. Methodology: Three experiments were performed. Experiment I evaluated the immunogenicity of purified recombinant InvG by (a) measuring anti-InvG antibodies using an enzyme-linked immunosorbent assay (ELISA) and (b) completing transcriptomic profiling of immune responses in vaccinated chickens. Vaccinated chickens were subsequently challenged with Salmonella Enteritidis to assess the efficacy of anti InvG antibodies in reducing intestinal colonization of Salmonella. Experiment II involved immunizing hens with InvG, to evaluate passive transfer of antibodies via egg yolk and the protective efficacy of maternally derived antibodies against Salmonella challenge. Passive transfer was assessed by measuring IgY antibodies in hen serum, egg yolk, and progeny serum, as well as secretory IgA (sIgA) antibodies in progeny intestinal washings using ELISA. Protective efficacy was evaluated by orally challenging one-day-old chicks with three different Salmonella serovars. Experiment III assessed the persistence of anti-InvG antibodies in the serum of vaccinated hens and their transfer into eggs following two doses of InvG. Results: InvG vaccination induced robust IgY antibody responses in hens, with efficient maternal antibody transfer to progeny via egg yolk. A statistically significant reduction in Salmonella colonization was observed in both vaccinated hens and their progeny. Conclusions: These findings demonstrate that InvG represents a promising subunit vaccine candidate for Salmonella control in poultry and warrants further investigation towards development as a broadly protective commercial poultry vaccine against Salmonella.

Background: Herpes zoster (HZ), caused by the reactivation of varicella-zoster virus (VZV), primarily affects elderly populations worldwide. Although current recombinant HZ vaccines show strong immunogenicity, their high cost and potential side effects may limit their widespread use. Therefore, developing a cost-effective HZ vaccine with improved safety profiles would have significant clinical and public health implications. Methods: Building upon our previously optimized truncated gE (tgE350) from VZV, we developed the tgE350 + Fe nanoparticle vaccine using SpyTag/SpyCatcher covalent conjugation. The tgE350 protein (with a SpyTag tag) and the Fe protein (with a SpyCatcher tag) were expressed in HEK293F and E. coli BL21, respectively, enabling spontaneous nanoparticle assembly. Protein expression and nanoparticle formation were confirmed through SDS-PAGE and negative-stain electron microscopy. BALB/c mice were inoculated with either tgE350 + Fe or tgE350 combined with Al and CpG adjuvants. Immune responses were evaluated using ELISpot and flow cytometry for cellular immunity, along with ELISA, VZV microneutralization, and fluorescent antibody membrane antigen (FAMA) assays for antibody titers. Histopathological examination of major organs ensured vaccine safety. Results: Compared with the truncated vaccine tgE350, the nanoparticle vaccine tgE350 + Fe significantly enhanced VZV neutralizing antibodies and specific antibody responses in mice without causing significant changes in lymphocyte populations (no difference from the control group). Moreover, the tgE350 + Fe group had significantly more lymphocytes secreting IFN-γ, IL-2, and IL-4 than the tgE350 group. No apparent pathological damage was observed in the heart, liver, spleen, or lungs of mice in any experimental group. Conclusions: This experiment successfully developed the HZ nanoparticle vaccine tgE350 + Fe. It enhanced VZV-specific neutralizing antibodies, generated better cellular and humoral immune responses, and demonstrated good safety.

Background/Objectives: Vaccination programs are highly effective public health interventions, yet parental hesitancy toward combination vaccines has led to growing demand for alternative vaccination schedules, defined in this study as parental requests to split or replace recommended combination vaccines with single-antigen vaccines for non-clinical reasons. While parental attitudes have been widely studied, little empirical evidence exists on the real-world use of single-antigen vaccines and their public health implications in countries with otherwise high coverage. This study examined the prevalence patterns and parental motivations for requesting such alternative vaccination schedules in Israel, where national guidelines recommend specific combination vaccines, including measles-mumps-rubella-varicella (MMRV) and the pentavalent diphtheria-tetanus-pertussis-inactivated polio-Haemophilus influenzae type b (DTaP+IPV+Hib) vaccines, but informal accommodations exist. Methods: A mixed-methods design was employed: a retrospective cohort analysis of vaccination data from 2018 to 2021 (before and during the COVID-19 pandemic) focused on measles (first dose at 12 months) and pertussis (four-dose primary series), followed by semi-structured interviews with Maternal and Child Health clinic providers, policymakers, and parents. Results: Alternative vaccination schedules involving single-antigen measles or pertussis vaccines are occasionally used despite official policy, accounting for less than 1% of vaccinations overall. Outcomes include delayed administration, lower uptake of combination vaccines, and incomplete protection in certain groups. Parents cited safety concerns, fear of immune overload, and mistrust of authorities. These concerns were often amplified by misinformation, while providers described balancing parental preferences with the need for adequate coverage. Conclusions: This study provides new evidence on how vaccine hesitancy translates into service utilization, highlights the tension between individualized parental decision-making and contribution to collective health, and underscores the need for communication, policy strategies and service designs that sustain high coverage while addressing community-specific concerns.

Background: A quadrivalent HPV vaccine (BPV) has been developed to prevent diseases caused by HPV types 6, 11, 16, and 18 for the first time in Iran. The BPV is composed of the papillomavirus major capsid protein L1, which serves as the primary target in the design of the prophylactic HPV vaccines. To enhance immunogenicity, BPV was formulated with an amorphous aluminum hydroxy phosphate sulfate adjuvant. Methods: The immunogenicity and safety of BPV were assessed through analyses of both humoral and cell-mediated immunity, single and repeated doses, and reproductive effects using animal models. Results: Acute toxicity assessments showed no abnormalities in ophthalmic examinations, biochemical profiles, hematological parameters, and gross pathology findings. Additionally, no mortality or abnormal clinical signs were observed during a 90-day repeated-dose toxicity study. While some inflammatory reactions were noted at the injection sites and in the liver tissues of BPV-treated groups, these reactions were resolved by day 90 after the initial BPV administration. Furthermore, no signs of toxicity were detected in F1 offspring, and no adverse effects were identified in maternal reproductive performance, fertility, or hematological or biochemical parameters throughout the study duration. The BPV candidate successfully induced T-cell proliferation and increased the proportions of CD₃⁺ CD₄⁺ and CD₃⁺ CD₈⁺ T cells. It also stimulated the secretion of both interferon gamma (IFN-γ) and interleukin-4 (IL-4) cytokines in splenocytes isolated from animal models after the third dose. Moreover, anti-HPV L1 IgG antibody production was confirmed on day 14 after administration of each of the three BPV vaccine doses. Conclusions: The findings suggest that BPV is a vaccine candidate that stimulates both cellular and humoral immunity and demonstrate its safety profile in animal models.

Yellow fever, a mosquito-borne viral hemorrhagic disease, remains a significant public health concern in endemic regions of Africa and South America. The development of the yellow fever vaccine marked a milestone in virology and immunization. In the 1930s, Max Theiler created the 17D live-attenuated vaccine, a breakthrough that has achieved global recognition and continues to underpin prevention strategies. This review outlines the historical evolution of the yellow fever vaccine, highlighting pivotal scientific advances, technological innovations, and global eradication initiatives. It examines the current landscape of immunization, focusing on the World Health Organization's Eliminate Yellow Fever Epidemics (EYE) strategy, ongoing efforts to address vaccine supply constraints, and persistent surveillance gaps. Future directions in vaccine development, including next-generation platforms and improved delivery systems, are also discussed, alongside the need for sustained research investment and international collaboration. As yellow fever emerges in previously non-endemic areas due to climate change and globalization, strengthening vaccination programs remains critical to preventing outbreaks and ensuring effective disease control.

Background: Emerging immune-evasive viral variants threaten the efficacy of current vaccines, underscoring the need for strategies that elicit broad and durable protection. Heterologous prime-boost regimens combining distinct vaccine platforms can enhance humoral and cellular immunity through complementary mechanisms.

Methods: Using an intramuscular immunization scheme aligned with clinical vaccination practice, CD-1 mice received homologous or heterologous prime-boost regimens combining a replication-deficient Orf virus (Parapoxvirus orf, ORFV)-based spike vaccine (ORFV-S) with the licensed adjuvanted recombinant protein vaccine VidPrevtyn Beta. Spike-specific humoral and cellular immune responses were assessed.

Results: ORFV-S alone induced potent and broad spike-specific IgG responses and achieved the strongest ACE2-binding inhibition across variants of concern. ORFV-S priming followed by VidPrevtyn Beta boosting markedly enhanced the magnitude and cross-variant breadth of antibody responses compared with homologous protein vaccination. Both homologous ORFV-S and heterologous regimens incorporating ORFV-S elicited strong CD4⁺ and CD8⁺ T-cell responses, whereas VidPrevtyn Beta alone induced only modest T-cell activity, demonstrating that ORFV-S effectively complements protein-based vaccines.

Conclusions: The ORFV-S vector represents a potent vaccine platform capable of inducing broad humoral and cellular immunity. Its use in heterologous prime-boost combinations enhances both antibody magnitude and breadth beyond homologous protein vaccination, supporting its application in vaccination strategies against evolving viral pathogens.

Background: Canine leishmaniasis is notoriously difficult to manage by chemotherapy alone, necessitating the consideration of supplemental or alternative treatment. Evidence is presented to support the feasibility of immunotherapy of diseased dogs through vaccination. Methods: The vaccine format used consisted of cultured promastigotes of Leishmania infantum, which were rapidly and completely killed by intracellularly generated singlet oxygen. A total of 33 owned dogs of different breeds and ages diagnosed positive for leishmaniasis were enrolled and divided into three groups for treatments as follows: (1) immunotherapy alone (9 dogs); (2) immunotherapy after chemotherapy (14 dogs); and (3) chemotherapy alone (10 dogs). All dogs in Groups 1 and 2 received intradermally three identical dosages of the vaccine format mentioned at the same schedules. The outcomes were assessed for one year at a post-treatment interval of 2-4 months by determining lymph node parasite loads and clinical scores based on established methodologies. Results: Spaghetti plots of the values for parasite loads obtained revealed that they scattered widely over time with a significant decline by 8-12 months post-treatment in all three groups. Sankey plots of clinical scores in stacked bars also showed that they followed erratic patterns of flow over time, albeit toward lower levels in all cases. Ordinal logistic regression analysis of clinical scores indicated that, while the odds for the emergence of severe clinical symptoms declined in all three groups, the lowest risk was associated with Group 2 dogs treated with immunotherapy after chemotherapy. The evidence presented thus suggests that immunotherapy of the diseased dogs with the vaccine format diminished their parasite loads and improved their clinical scores, especially when applied after chemotherapy. Dogs in Groups 1 and 2 that received immunotherapy, on average, lived twice as long as those in Group 3 that received chemotherapy alone. The risk of death estimated by analysis of the clinical scores using the Cox proportional hazard model was also found to be lower for Groups 1-2 dogs receiving immunotherapy than those in Group 3 receiving chemotherapy alone. Conclusions: Post-therapeutic survival time thus may be an additional parameter suitable to assess treatment efficacy by vaccination. In vitro approaches to mitigate some limitations of this study were proposed for future investigation.

Background: Patients with end-stage renal disease (ESRD) on hemodialysis are at increased risk for severe influenza, and underlying immune dysfunction may limit vaccine-induced protection. Methods: This observational open-label study evaluated immune responses in 93 hemodialysis patients vaccinated with seasonal inactivated influenza vaccine (IIV) during the 2019-2020 (n = 22) and 2023-2024 (n = 71) seasons. Immune responses were comprehensively assessed using hemagglutination inhibition and microneutralization assays to measure antibody levels, together with flow cytometry analysis of key immune cell populations, including plasmablasts, T-follicular helper cells (Tfh), and effector memory T cells (Tem). Results: During the 2019-2020 season, antibody responses in hemodialysis patients were comparable to those in healthy volunteers in both younger (18-60 years) and older (over 60) age groups. By day 7 post-vaccination, there was a pronounced increase in activated Tfh1 cells, coinciding with a surge in plasmablasts and a rise in antigen-specific B cells. This was accompanied by a T-cell response mediated by IFNγ-producing and polyfunctional CD4+ Tem cells. In the 2023-2024 season, revaccination was associated with higher baseline antibody levels but did not alter subsequent response kinetics to A/H1N1pdm, A/H3N2, and B/Yamagata antigens. In contrast, responses to B/Victoria were higher in revaccinated patients throughout the entire observation period. Conclusions: Our findings confirm that standard-dose IIV vaccination is beneficial for hemodialysis patients, inducing robust and adequate humoral and T-cell immune responses.

Background/objectives: Human papillomavirus (HPV) represents a major public health challenge due to its high prevalence and the complications arising from infection. The aim of the study was to investigate the reasons for adherence to the HPV vaccination campaign offered by the University of Milan to its students.

Methods: A questionnaire, distributed via QR code, was utilized to investigate the motivations behind participation in the vaccination campaign, as well as the characteristics of the population participating in the vaccination campaign carried out at the University of Milan. Concurrently, a comprehensive analysis of the characteristics of students was also carried out at the vaccination sites where it was conducted, categorizing them into university hospitals and university campuses.

Results: A comparison of vaccination sites revealed a significant disparity between hospitals and universities with regard to gender, age, and faculty. A higher average age (25 versus 24 years) and a higher prevalence of females (53.9% versus 51.1%) were observed in hospitals. The findings of the regression model demonstrate that demographic factors exert an influence on only two reasons for participation, with male gender proving a predictive factor for the response option entitled "It is a responsibility towards one's partner(s)". Furthermore, enrolment in a course of study has been found to correlate positively with the response option entitled "I have been convinced by advertising campaigns/friends/acquaintances".

Conclusions: A vaccination campaign implemented within educational institutions is a fundamental strategy for enhancing vaccination uptake rates among young population. Conversely, the utilization of health promotion interventions, such as pre-vaccination promotional campaigns, does not seem to be a pivotal factor in enhancing uptake.

Background/Objectives: Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract infection in young children, especially during infancy, resulting in substantial morbidity and mortality. Methods: Acknowledging the real-world evidence on RSV immunization, the College of Pediatrics, Academy of Medicine of Malaysia, has appointed an expert panel to develop a position paper on recommendations for infant and/or maternal vaccination against childhood RSV, specifically in the Malaysian context with year-round RSV activity. Results: Recognizing the potential constraints and limitations in the implementation process, the expert panel recommends targeted immunization with long-acting RSV monoclonal antibody (mAb) for high-risk infants as a pragmatic first step, with subsequent scale-up to universal immunization of infants when resources permit. Conclusions: Immunization is the most effective strategy to prevent RSV-related lower respiratory tract infection in childhood. Year-round maternal vaccination between 28 and 36 weeks' gestation, combined with immunization at six months for all infants, may potentially circumvent the unclear seasonality.