Combination of Live and Inactivated Salmonella Vaccines to Protect Against Fowl Typhoid in Laying Hens.

Fowl typhoid (FT) caused by Salmonella Gallinarum (SG) is a poultry disease distributed worldwide that has been eradicated in commercial production of many developed countries but still persists in many developing countries. Vaccination is one of the main strategies to reduce mortality, clinical signs, and vertical or horizontal transmission. The aim of this work was to assess the protection against FT conferred by vaccines based on Salmonella Enteritidis (SE), SG, or a combination. Five experimental groups of birds, vaccinated with different live or inactivated SG and SE vaccines were included in the trial: 1) two doses of a SG-SE bivalent inactivated vaccine; 2) four doses of the live attenuated SE vaccine; 3) three doses of the live attenuated SE vaccine and two doses of the SG-SE bivalent inactivated vaccine; 4) two doses of the live attenuated SG9R vaccine; and 5) unvaccinated birds. At 28 wk of age, all hens were challenged with a virulent strain of SG, and mortality was recorded during the subsequent 15 days. The results showed that the plan that included only the inactivated vaccine did not show significant protection (P = 1), while the plan based on the administration of the attenuated strain of SE significantly reduced mortality in the group of birds (P = 0.0309). However, the highest levels of protection were obtained in the group of hens immunized with the combination of the inactivated vaccine and the live attenuated SE strain (P < 0.0001), which was statistically similar to the homologous protection conferred by the SG 9R strain, a vaccine used in many countries to control FT. These results demonstrate that the combination of existing vaccines together with strict biosecurity measures on farms may help improve the control of the pathogen in countries where FT in an emerging or reemerging disease.

Nota de investigación- Combinación de vacunas vivas e inactivadas contra Salmonella para proteger contra la tifoidea aviar en gallinas de postura. La tifoidea aviar (FT) causada por Salmonella enterica serotipo Gallinarum biovar Gallinarum (SG) es una enfermedad distribuida en todo el mundo que ha sido erradicada de la producción av'icola comercial de muchos pa'ises desarrollados pero que aún persiste en muchos pa'ises en desarrollo. La vacunación es una de las principales estrategias para reducir la mortalidad, los signos cl'inicos y la transmisión vertical u horizontal. El objetivo de este trabajo fue evaluar la protección contra la tifoidea aviar conferida por vacunas elaboradas con Salmonella enterica serotipo Enteritidis (SE), SG o una combinación de ellas. Se incluyeron en el ensayo cinco grupos experimentales de aves, vacunadas con diferentes vacunas de SG y SE vivas o inactivadas: 1) dos dosis de una vacuna bivalente inactivada de SG y SE; 2) cuatro dosis de la vacuna SE viva atenuada; 3) tres dosis de vacuna SE viva atenuada y dos dosis de vacuna bivalente inactivada SG y SE; 4) dos dosis de la vacuna SG 9R viva atenuada; y 5) aves no vacunadas. A las 28 semanas de edad, todas las gallinas fueron expuestas a una cepa virulenta de SG y se registró la mortalidad durante los 15 d'ias siguientes. Los resultados mostraron que el plan que inclu'ia solo la vacuna inactivada no mostró protección significativa (P=1), mientras que el plan basado en la administración de la cepa atenuada de S. Enteritidis redujo significativamente la mortalidad en el grupo de aves (P = 0,0309). Sin embargo, los mayores niveles de protección se obtuvieron en el grupo de gallinas inmunizadas con la combinación de la vacuna inactivada y la cepa viva atenuada de SE (P < 0,0001), la cual fue estad'isticamente similar a la protección homóloga conferida por la cepa de SG 9R, que es una vacuna utilizada en muchos pa'ises para controlar la tifoidea aviar. Estos resultados demuestran que la combinación de las vacunas existentes junto con estrictas medidas de bioseguridad en las granjas puede ayudar a mejorar el control del patógeno en pa'ises donde la tifoidea aviar es una enfermedad emergente o reemergente.

Protection of Broiler Chickens Against Necrotic Enteritis by Intrapulmonary Delivery of a Live Clostridium perfringens Vaccine Exploiting the Gut-Lung-Axis Concept.

Clostridium perfringens (CP)-induced necrotic enteritis (NE) is an economically important disease in the broiler chicken industry. The incidence of NE is common in 3-to-6-wk-old broiler chickens, once maternal antibodies start declining. Developing an effective vaccination strategy against NE, preferably delivering a single dose of vaccine at hatch to protect broiler chickens against NE without a booster vaccine, is an enormous challenge. The objective of this study was to induce mucosal immunity in the intestines against NE by intrapulmonary (IPL) delivery of a live CP vaccine at hatch, exploiting the gut-lung-axis (GLA) concept by vaccine delivery following in ovo administration of cytosine-phosphorothioate-guanine oligodeoxynucleotides (CpG-ODN) to induce immune cell maturation in the lungs. Experiments were conducted to explore the dose of CP and immune protection against heterologous CP challenge, and to study the efficacy of IPL delivery of a CP vaccine without a booster. Additional studies were conducted to measure serum immunoglobulin (Ig)Y, mucosal IgA, and histopathology of lungs following vaccination. Delivery of a live CP vaccine by the IPL route, with or without in ovo CpG-ODN, provided significant protection against NE (P < 0.0001). Systemic IgY and mucosal IgA against CP were correlated with protection against NE. There was no necrosis or inflammation in the pulmonary parenchyma. There was a low number of CP isolated from the lungs following live CP delivery by the IPL route. A significant influx of (P < 0.001) of CD8+ T cells and macrophages were noted in the lungs 2 days following live CP delivery by the IPL route. IPL delivery of a live CP vaccine, rather than inactivated CP, provided better protection. This study demonstrated the utility in exploiting the GLA concept in vaccine delivery in broiler chickens.

Protección de pollos de engorde contra la enteritis necrótica mediante la administración intrapulmonar de una vacuna viva de Clostridium perfringens que aprovecha el concepto del eje intestino-pulmón. La enteritis necrótica (NE) inducida por Clostridium perfringens (CP) es una enfermedad económicamente importante en la industria de los pollos de engorde. La incidencia de enteritis necrótica es común en pollos de engorde de tres a seis semanas de edad, una vez que los anticuerpos maternos comienzan a disminuir. El desarrollo de una estrategia de vacunación eficaz contra la enteritis necrótica, preferiblemente administrando una dosis única de vacuna en la eclosión para proteger a los pollos de engorde contra dicha enfermedad sin la necesidad de aplicar una vacuna de refuerzo, es un desafío importante. El objetivo de este estudio fue inducir inmunidad de mucosas en los intestinos contra la enteritis necrótica mediante la administración intrapulmonar (IPL) de una vacuna de C. perfringens viva en la eclosión, explotando el concepto del eje intestino-pulmón (GLA) mediante la administración de la vacuna después de la administración in ovo de citosin oligodesoxinucleótidos de fosforotioato-guanina (CpG-ODN) para inducir la maduración de las células inmunitarias en los pulmones. Se realizaron experimentos para explorar la dosis de C. perfringens y la protección inmune contra la exposición heteróloga a C. perfringens, y para estudiar la eficacia de la administración intrapulmonar de una vacuna C. perfringens sin refuerzo. Se realizaron estudios adicionales para medir la inmunoglobulina (Ig)Y sérica, la IgA de mucosas y la histopatología de los pulmones después de la vacunación. La administración de una vacuna de C. perfringens viva por vía intrapulmonar, con o sin CpG-ODN in ovo, proporcionó una protección significativa contra la enteritis necrótica (P < 0.0001). La IgY sistémica y la IgA mucosa contra C. perfringens se correlacionaron con la protección contra la enteritis necrótica. No hubo necrosis ni inflamación en el parénquima pulmonar. Hubo un número bajo de C. perfringens aislado de los pulmones después de la administración de la vacuna viva contra C. perfringens por vía intrapulmonar. Se observó una afluencia significativa (P < 0.001) de células T CD8+ y macrófagos en los pulmones dos días después de la administración de C. perfringens viva por vía intrapulmonar. La administración mediante vía intrapulmonar de una vacuna viva contra C. perfringens, en lugar de la vacuna contra C. perfringens inactivada, proporcionó una mejor protección. Este estudio demostró la utilidad de explotar el concepto del eje intestino-pulmón en la administración de vacunas en pollos de engorde.

Long-term immunogenicity of the SA14-14-2 Japanese encephalitis (JE) vaccine (CD.JEVAX®) booster following chimeric JE (IMOJEV®) vaccine priming in Thai children.

Japanese encephalitis (JE) is a significant public health concern in Asia, particularly in children, where vaccination plays a crucial role in prevention. In this study, we investigated the immunogenicity and safety of two different live-attenuated JE vaccines used as primary and booster doses. Fifty healthy participants aged 1-3 years, who were primed with the chimeric JE vaccine IMOJEV® a year earlier, received a booster dose of the SA14-14-2 JE vaccine CD.JEVAX®. To evaluate the immune response, JE-neutralizing antibody titers were assessed on day 0 (pre-booster), day 30, and annually from 1 to 5 years post-booster using the 50% plaque reduction neutralization test (JEPRNT50). The assessment revealed strong immunogenicity 30 d post-booster, with a geometric mean titer of 2092.4 [95% confidence interval (CI): 1473.9-2970.5] and a seroprotection rate of 100%, which gradually decreased to 97.5% at 5 years post-booster. No severe adverse events were observed. The most common reaction within 7 d of vaccination was fever (20%; 95% CI: 10.7-32.3). These results indicate that a booster dose of CD.JEVAX® elicits a strong immune response in children previously vaccinated with IMOJEV® while maintaining a good safety profile, thus supporting the interchangeability of these two live-attenuated JE vaccines. Registered at www.thaiclinicaltrials.org (TCTR ID: TCTR20221102003), our study suggests that CD.JEVAX® can be a viable option for booster vaccination in JE prevention programs, potentially enhancing vaccine flexibility and accessibility.

Protection Evaluation of a New Attenuated ASFV by Deletion of the L60L and CD2v Genes against Homologous Challenge.

African swine fever (ASF) is an acute infectious disease with a high mortality rate in both domestic and wild boars. Commercial vaccines or antiviral drugs for ASF were not available due to the complex diversity of the structure and genome of its pathogen African swine fever virus (ASFV). In recent years, there have been many reports on candidate strains of attenuated vaccines for ASFV. In this study, we obtained a recombinant virus named SY18ΔL60LΔCD2v by simultaneously deleting the L60L gene and CD2v gene from highly virulent strain SY18. In vitro, SY18ΔL60LΔCD2v displayed a decreased growth kinetic compared to that of parental SY18. In vivo, high doses (105 TCID50) of SY18ΔL60LΔCD2v can protect pigs (5/5) from attacks by the parental SY18 strain (102 TCID50). Low doses (102 TCID50) of SY18ΔL60LΔCD2v only protected 20% of pigs (1/5) from attacks by the parental SY18 strain (102 TCID50). The results indicated that the absence of these two genes in SY18 could induce protection against the homologous parental strain, and there were no obvious clinical symptoms or viremia. These results indicate that the SY18ΔL60LΔCD2v strain can serve as a new live attenuated vaccine candidate for the prevention and control of ASFV infection.

The impact of the implementation of the two-dose varicella vaccine immunization strategy in Quzhou: A retrospective birth cohort study.

Varicella is a vaccine-preventable disease caused by the varicella zoster virus (VZV), but the varicella incidence among children has increased in recent years. This was a retrospective birth cohort study based on the Zhejiang Provincial Immune Information System (ZJIIS) and the China Information System for Disease Control and Prevention (CISDCP) in Quzhou. A total of 1,291 clinically diagnosed varicella cases born from 2009 to 2014 were collected during 2009-2023, which were analyzed the impact of changes in vaccination strategy on the incidence of varicella based on the Cox-proportional hazards model. It was observed that the onset age of varicella shifted to the older age group and later to 9-11 years. After the change to the two-dose varicella vaccination strategy, the population affected by varicella was concentrated among students and received more than one dose of live attenuated varicella vaccine (VarV). Based on the Coxproportional hazards model and adjusting for all covariates, the risk of varicella infection in children decreased after the introduction of the two-dose varicella vaccination strategy (HR = 0.04, 95% CI: 0.03-0.05). Meanwhile, the Kaplan-Meier curves also showed that the hazards were lower after the change in vaccination strategy. It is recommended that two doses of VarV should be included in the national immunization schedule and that full vaccination should be completed approximately four years after the first dose.

Rotavirus-Specific Maternal Serum Antibodies and Vaccine Responses to RV3-BB Rotavirus Vaccine Administered in a Neonatal or Infant Schedule in Malawi.

High titres of rotavirus-specific maternal antibodies may contribute to lower rotavirus vaccine efficacy in low- and middle-income countries (LMICs). RV3-BB vaccine (G3P[6]) is based on a neonatal rotavirus strain that replicates well in the newborn gut in the presence of breast milk. This study investigated the association between maternal serum antibodies and vaccine response in infants administered the RV3-BB vaccine. Serum was collected antenatally from mothers of 561 infants enrolled in the RV3-BB Phase II study conducted in Blantyre, Malawi, and analysed for rotavirus-specific serum IgA and IgG antibodies using enzyme-linked immunosorbent assay. Infant vaccine take was defined as cumulative IgA seroconversion (≥3 fold increase) and/or stool vaccine shedding. Maternal IgA or IgG antibody titres did not have a negative impact on vaccine-like stool shedding at any timepoint. Maternal IgG (but not IgA) titres were associated with reduced take post dose 1 (p < 0.005) and 3 (p < 0.05) in the neonatal vaccine schedule group but not at study completion (week 18). In LMICs where high maternal antibodies are associated with low rotavirus vaccine efficacy, RV3-BB in a neonatal or infant vaccine schedule has the potential to provide protection against severe rotavirus disease.

A Quadruple Gene-Deleted Live BoHV-1 Subunit RVFV Vaccine Vector Reactivates from Latency and Replicates in the TG Neurons of Calves but Is Not Transported to and Shed from Nasal Mucosa.

Bovine herpesvirus type 1 (BoHV-1) establishes lifelong latency in trigeminal ganglionic (TG) neurons following intranasal and ocular infection in cattle. Periodically, the latent virus reactivates in the TG due to stress and is transported anterogradely to nerve endings in the nasal epithelium, where the virus replicates and sheds. Consequently, BoHV-1 is transmitted to susceptible animals and maintained in the cattle population. Modified live BoHV-1 vaccine strains (BoHV-1 MLV) also have a similar latency reactivation. Therefore, they circulate and are maintained in cattle herds. Additionally, they can regain virulence and cause vaccine outbreaks because they mutate and recombine with other circulating field wild-type (wt) strains. Recently, we constructed a BoHV-1 quadruple mutant virus (BoHV-1qmv) that lacks immune evasive properties due to UL49.5 and glycoprotein G (gG) deletions. In addition, it also lacks the gE cytoplasmic tail (gE CT) and Us9 gene sequences designed to make it safe, increase its vaccine efficacy against BoHV-1, and restrict its anterograde neuronal transport noted above. Further, we engineered the BoHV-1qmv-vector to serve as a subunit vaccine against the Rift Valley fever virus (BoHV-1qmv Sub-RVFV) (doi: 10.3390/v15112183). In this study, we determined the latency reactivation and nasal virus shedding properties of BoHV-1qmv (vector) and BoHV-1qmv-vectored subunit RVFV (BoHV-1qmv sub-RVFV) vaccine virus in calves in comparison to the BoHV-1 wild-type (wt) following intranasal inoculation. The real-time PCR results showed that BoHV-1 wt- but not the BoHV-1qmv vector- and BoHV-1qmv Sub-RVFV-inoculated calves shed virus in the nose following dexamethasone-induced latency reactivation; however, like the BoHV-1 wt, both the BoHV-1qmv vector and BoHV-1qmv Sub-RVFV viruses established latency, were reactivated, and replicated in the TG neurons. These results are consistent with the anterograde neurotransport function of the gE CT and Us9 sequences, which are deleted in the BoHV-1qmv and BoHV-1qmv Sub-RVFV.

Next generation yellow fever vaccine induces an equivalent immune and transcriptomic profile to the current vaccine: observations from a phase I randomised clinical trial.

BACKGROUND: Yellow fever (YF), a mosquito-borne acute viral haemorrhagic illness, is endemic to many tropical and subtropical areas of Africa and Central and South America. Vaccination remains the most effective prevention strategy; however, as repeated outbreaks have exhausted vaccine stockpiles, there is a need for improved YF vaccines to meet global demand. A live-attenuated YF vaccine candidate (referred to as vYF) cloned from a YF-17D vaccine (YF-VAX®) sub-strain, adapted for growth in Vero cells cultured in serum-free media, is in clinical development. We report the innate and adaptive immune responses and the transcriptome profile of selected genes induced by vYF. METHODS: Healthy adults aged 18-60 years were randomised at a 1:1:1:1 ratio to receive one dose of vYF at 4, 5 or 6 Log CCID50 or YF-VAX (reference vaccine), administered subcutaneously in the upper arm (ClinicalTrials.gov identifier: NCT04142086). Blood/serum samples were obtained at scheduled time points through 180 days (D180) post-vaccination. The surrogate endpoints assessed were: serum cytokine/chemokine concentrations, measured by bead-based Multiplex assay; peripheral blood vYF-specific IgG and IgM memory B cell frequencies, measured by FluoroSpot assay; and expression of genes involved in the immune response to YF-17D vaccination by RT-qPCR. FINDINGS: There was no increase in any of the cytokine/chemokine concentrations assessed through D14 following vaccination with vYF or YF-VAX, except for a slight increase in IP-10 (CXCL10) levels. The gene expression profiles and kinetics following vaccination with vYF and YF-VAX were similar, inclusive of innate (antiviral responses [type-1 interferon, IFN signal transduction; interferon-stimulated genes], activated dendritic cells, viral sensing pattern recognition receptors) and adaptive (cell division in stimulated CD4+ T cells, B cell and antibody) immune signatures, which peaked at D7 and D14, respectively. Increases in vYF-specific IgG and IgM memory B cell frequencies at D28 and D180 were similar across the study groups. INTERPRETATION: vYF-induced strong innate and adaptive immune responses comparable to those induced by YF-VAX, with similar transcriptomic and kinetic profiles observed. FUNDING: Sanofi.

Breaking Latent Infection: How ORF37/38-Deletion Mutants Offer New Hope against EHV-1 Neuropathogenicity.

Equid alphaherpesvirus 1 (EHV-1) has been linked to the emergence of neurological disorders, with the horse racing industry experiencing significant impacts from outbreaks of equine herpesvirus myeloencephalopathy (EHM). Building robust immune memory before pathogen exposure enables rapid recognition and elimination, preventing infection. This is crucial for effectively managing EHV-1. Removing neuropathogenic factors and immune evasion genes to develop live attenuated vaccines appears to be a successful strategy for EHV-1 vaccines. We created mutant viruses without ORF38 and ORF37/38 and validated their neuropathogenicity and immunogenicity in hamsters. The ∆ORF38 strain caused brain tissue damage at high doses, whereas the ∆ORF37/38 strain did not. Dexamethasone was used to confirm latent herpesvirus infection and reactivation. Dexamethasone injection increased viral DNA load in the brains of hamsters infected with the parental and ∆ORF38 strains, but not in those infected with the ∆ORF37/38 strain. Immunizing hamsters intranasally with the ∆ORF37/38 strain as a live vaccine produced a stronger immune response compared to the ∆ORF38 strain at the same dose. The hamsters demonstrated effective protection against a lethal challenge with the parental strain. This suggests that the deletion of ORF37/38 may effectively inhibit latent viral infection, reduce the neuropathogenicity of EHV-1, and induce a protective immune response.

Live-attenuated PruΔgra72 strain of Toxoplasma gondii induces strong protective immunity against acute and chronic toxoplasmosis in mice.

BACKGROUND: Toxoplasma gondii is an intracellular opportunistic pathogenic protozoan that poses serious threats, particularly in immunocompromised individuals. In the absence of a robust prophylactic measure, the mitigation and management of toxoplasmosis present formidable challenges to public health. We recently found that GRA72 plays an important role in parasitophorous vacuole (PV) morphology, growth and virulence of T. gondii. However, whether gra72-deficient strain can be used as a vaccine remains unknown. METHODS: We first examined the attenuated virulence of gra72 gene knockout strain (PruΔgra72) and the parasite load in organs of the infected mice. Subsequently, we evaluated the immune-protective effects of the PruΔgra72 vaccination against challenge with various types of T. gondii tachyzoites and Pru cysts. Furthermore, levels of antibodies and cytokines induced by PruΔgra72 vaccination were examined. Statistical analysis was conducted by Student's t-test or Mantel-Cox log-rank test based on data obtained from three independent experiments with GraphPad Prism 8.0. RESULTS: We found that PruΔgra72 strain exhibited a significantly attenuated virulence even at the highest dose of 5 × 107 tachyzoites in Kunming mice model. The significant decrease of brain cyst burden and parasite load in the organs of the PruΔgra72-infected mice suggested its potentiality as a live-attenuated vaccine. Hence, we explored the protective immunity of PruΔgra72 vaccination against toxoplasmosis. Results showed that vaccination with 5 × 106 PruΔgra72 tachyzoites triggered a strong and sustained Th1-biased immune response, marked by significantly increased levels of anti-T. gondii IgG antibodies, and significantly higher levels of Th1 type cytokines (IL-2, IL-12 and IFN-γ) compared to that of Th2 type (IL-4 and IL-10). Vaccination with 5 × 106 PruΔgra72 tachyzoites in mice conferred long-term protection against T. gondii infection by less virulent tachyzoites (ToxoDB#9 PYS and Pru strains) and Pru cysts, provided partial protection against acute infection by high virulent Type I RH tachyzoites and significantly decreased brain cyst burden of chronically infected mice. CONCLUSIONS: The avirulent PruΔgra72 induced strong protective immunity against acute and chronic T. gondii infection and is a promising candidate for developing a safe and effective live-attenuated vaccine against T. gondii infection.

The effect of early administration of antibiotics or feeding a diet containing coccidiostats on the level of their accumulation in liver and the redox status of turkeys.

Early administration of antibiotics may worsen the functioning of the turkeys' antioxidant system. It was also assumed that the longer the time of administration of an antibiotic, e.g. a coccidiostat, the greater the risk of its accumulation in the liver. The study aimed to determine whether early administration of antibiotics or feeding a diet containing coccidiostats causes accumulation in the liver and whether it affects the deterioration of the antioxidant system, and whether preventive vaccinations can intensify it. A total of 3 080 female turkeys were randomly allocated to eight groups. The experiment had a two-factorial design, with four treatments (C, M, E, D) and two groups of birds (vaccinated +, unvaccinated -). The C group did not receive the coccidiostat or antibiotics. Group M was administered monensin at 90 mg/kg feed for 56 days of life. Group E received enrofloxacin at 10 mg/kg BW, and group D received doxycycline at 50 mg/kg BW, added to drinking water, for the first 5 days of life. One-day-old turkeys from groups C+, M+, E+, and D+ were administered live-attenuated vaccines against turkey rhinotracheitis and Newcastle disease by coarse spray; 28-day-old birds were administered a subcutaneously injected inactivated vaccine against Ornithobacterium rhinotracheale. Turkeys from groups C-, M-, E-, and D- were not vaccinated. It was determined that as a result of administration of enrofloxacin or doxycycline until the 5th day of life, biotransformation of these antibiotics occurred in the liver until the 56th day of life of the turkeys, which was confirmed by their lower level than the Maximum Residue Level. Because the concentration of monensin in the liver of turkeys gradually increased with the extension of the time of its administration in the diet, it is probable that discontinuing its addition a day before the slaughter of birds will result in the presence of this coccidiostat in the liver of turkeys. Despite the accumulation of monensin in the liver of turkeys, this coccidiostat did not increase oxidative reactions in the organism of turkeys. Vaccination of turkeys can reduce oxidative reactions and apoptosis in the body. However, the effect of the redox system reaction is different immediately after vaccination, which is due to the mechanism of action of the immune system. If it is necessary to administer an antibiotic in the early rearing period, the effects of doxycycline on the organism's immunity including antioxidant defence will be less severe than those of enrofloxacin.

Novel recombinant vaccinia virus-vectored vaccine affords complete protection against homologous Borrelia burgdorferi infection in mice.

The rising prevalence of Lyme disease (LD) in North America and Europe has emerged as a pressing public health concern. Despite the availability of veterinary LD vaccines, no vaccine is currently available for human use. Outer surface protein C (OspC) found on the outer membrane of the causative agent, Borrelia burgdorferi, has been identified as a promising target for LD vaccine development due to its sustained expression during mammalian infection. However, the efficacy and immunological mechanisms of LD vaccines solely targeting OspC are not well characterized. In this study, we developed an attenuated Vaccinia virus (VV) vectored vaccine encoding type A OspC (VV-OspC-A). Two doses of the VV-OspC-A vaccine conferred complete protection against homologous B. burgdorferi challenge in mice. Furthermore, the candidate vaccine also prevented the development of carditis and lymph node hyperplasia associated with LD. When investigating the humoral immune response to vaccination, VV-OspC-A was found to induce a robust antibody response predominated by the IgG2a subtype, indicating a Th1-bias. Using a novel quantitative flow cytometry assay, we also determined that elicited antibodies were capable of inducing antibody-dependent cellular phagocytosis in vitro. Finally, we demonstrated that VV-OspC-A vaccination generated a strong antigen-specific CD4+ T-cell response characterized by the secretion of numerous cytokines upon stimulation of splenocytes with OspC peptides. This study suggests a promising avenue for LD vaccine development utilizing viral vectors targeting OspC and provides insights into the immunological mechanisms that confer protection against B. burgdorferi infection.

A naturaly attenuated largemouth bass ranavirus strain provided protection for Micropterus salmoides by immersion immunization.

Largemouth bass ranavirus (LMBV) causes disease outbreaks and high mortality at all stages of largemouth bass farming. Therefore, live vaccine development is critical for largemouth bass prevention against LMBV by immersion immunization. Herein, an attenuated LMBV strain with good immunogenicity, designated as LMBV-2007136, was screened from the natural LMBV strains bank through challenge assay and immersion immunization experiment. After determing the safe concentration range of LMBV-2007136, the minimum immunizing dose of immersion immunization was verified. When largemouth bass were vaccinated by immersion at the lowest concentration of 102.0 TCID50/mL, all of fish were survival post virulent LMBV challenge, and the relative percent survival (RPS) was 100 %. And the immune gene expression levels of IL-10, IL-12, IFN-γ, and IgM in the spleen and kidney post-vaccination were significantly up-regulated compared to the control group, but TNF-α expression showed no significant changes. The safety and efficacy of LMBV-2007136 at passages P8, P13, and P18 were futher assessed, and no death of largemouth bass was observed within 21 days post-immunization and RPS of three vaccination groups was 100 %, suggesting that the safety and efficacy of the attenuated strain at different passages was stable. Furthermore, in the virulence reversion test, the attenuated strain was propagated through 5 times in largemouth bass by intraperitoneal injection and no abnormality and mortality were observed, further proving the attenuated vaccine candidate LMBV-2007136 was safe. These results proved that LMBV-2007136 could be a promising candidate for a live vaccine to protect largemouth bass from LMBV disease.

Syncope after live attenuated influenza vaccine: Reports to the Vaccine Adverse Event Reporting System (2003-2024).

Vasovagal syncope, or fainting, can be triggered by various stimuli, including medical procedures. Syncope after vaccination has been reported, most commonly among adolescents, and can result in injuries. Using the Vaccine Adverse Event Reporting System (VAERS), we reviewed and summarized reports of syncope after live attenuated influenza vaccine, intranasal (LAIV) administered as the sole vaccine (i.e., no concomitant injections). From June 17, 2003 (date of LAIV licensure in the US) through May 31, 2024, VAERS received 50 reports of syncope after LAIV. Nearly half (23; 46 %) pertained to individuals 10-19 years of age. While the vast majority of reports (35; 70 %) did not describe any injuries, 15 people (30 %) were injured, most commonly by falling and hitting their head or face. Twenty-two people (44 %) required evaluation in the emergency department or doctor's office, including an individual who lost consciousness while he was driving home from the vaccination appointment. He did not report any injuries, but the car was severely damaged. Nearly three-quarters of people (37; 74 %) developed syncope within 15 min after vaccination, but fewer than half of reports (24; 48 %) stated that the patient had waited in the observation area for at 15 min. Based on approximately 111.9 million doses of LAIV distributed in the US during the same time period, the reporting rate is approximately 0.4 per million doses, suggesting that syncope following LAIV is rare. The information summarized here may enable clinicians, patients, and caregivers to make a more informed decision regarding preventing injuries that may occur following LAIV-related syncope.

Health impact of rotavirus vaccination in China.

Rotavirus (RV) vaccines have demonstrated substantial effectiveness in reducing the healthcare burden caused by gastroenteritis (RVGE) worldwide. This study aims to understand the differential impact of RV vaccination in reducing RVGE burden in children under 7 years old in China. A Markov Model was used to investigate the health impact of introducing two different RV vaccines into the Chinese population. The analysis was conducted for RV5, a live pentavalent human-bovine reassortant vaccine, and Lanzhou Lamb RV (LLR), a live-attenuated monovalent RV vaccine, separately, by comparing the strategy of each vaccine to no vaccination within a Chinese birth cohort, including 100,000 children modeled until 7 years of age. The vaccination scenario assumed a vaccination coverage of 2.5%, 2.5%, 90% and 5% for doses one, two, three and no vaccine, respectively, for both vaccines. Strategies with RV5, LLR, and no vaccination were associated with 9,895, 49,069, and 64,746 symptomatic RV infections, respectively. RV5 and LLR were associated with an 85% and 24% reduction in the total symptomatic RV infections, respectively, suggesting that the health benefits of RV5 are at least three-fold greater than those associated with the LLR. Further, strategies with RV5 and LLR resulted in an estimated 206 and 59-year increase in quality-adjusted life years (QALYs), respectively. Sensitivity and scenario analyses supported the robustness of the base-case findings. Use of RV vaccine is expected to improve RV-associated health outcomes and its adoption will help alleviate the burden of RVGE in China. RV5 use will result in significantly better health outcomes.

Updating and Refining of Economic Evaluation of Rotavirus Vaccination in Spain: A Cost-Utility and Budget Impact Analysis.

Two vaccines against rotavirus diseases, Rotarix® and RotaTeq®, are being marketed in Spain; but rotavirus is not presently among the diseases covered by universal vaccination in Spain. The aim of this study was to assess the efficiency of extending Spain's current targeted rotavirus vaccination strategy including only preterm babies, to a policy of universal vaccination. A de novo cohort-based Markov model was built to evaluate the efficiency of three compared rotavirus vaccination strategies in Spain: targeted, universal, and no vaccination. Using Rotarix® or RotaTeq®, we compared the cost-utility of these strategies from both a societal perspective and Spanish National Health System (SNHS) perspective. The model represents the most important clinical events conceivably linked to rotavirus infection. Efficacy, effectiveness, safety, costs, and utilities were identified by systematic reviews. Incremental cost-utility ratio (ICUR) is EUR 23,638/QALY (Quality-Adjusted Life Year) for targeted vaccination with Rotarix® compared with no vaccination. The ICUR for the rest of the strategies evaluated are above EUR 30,000/QALY. The sensitivity analysis shows price as the only parameter that could make the universal vaccination strategy efficient. Considering a threshold of EUR 25,000/QALY, only targeted vaccination with Rotarix® would be efficient from societal perspective. Price drops of 36.9% for Rotarix® and 44.6% for RotaTeq® would make universal vaccination efficient.

A Non-Hemadsorbing Live-Attenuated Virus Vaccine Candidate Protects Pigs against the Contemporary Pandemic Genotype II African Swine Fever Virus.

African swine fever (ASF) is a highly contagious and severe hemorrhagic transboundary swine viral disease with up to a 100% mortality rate, which leads to a tremendous socio-economic loss worldwide. The lack of safe and efficacious ASF vaccines is the greatest challenge in the prevention and control of ASF. In this study, we generated a safe and effective live-attenuated virus (LAV) vaccine candidate VNUA-ASFV-LAVL3 by serially passaging a virulent genotype II strain (VNUA-ASFV-L2) in an immortalized porcine alveolar macrophage cell line (3D4/21, 50 passages). VNUA-ASFV-LAVL3 lost its hemadsorption ability but maintained comparable growth kinetics in 3D4/21 cells to that of the parental strain. Notably, it exhibited significant attenuation of virulence in pigs across different doses (103, 104, and 105 TCID50). All vaccinated pigs remained healthy with no clinical signs of African swine fever virus (ASFV) infection throughout the 28-day observation period of immunization. VNUA-ASFV-LAVL3 was efficiently cleared from the blood at 14-17 days post-infection, even at the highest dose (105 TCID50). Importantly, the attenuation observed in vivo did not compromise the ability of VNUA-ASFV-LAVL3 to induce protective immunity. Vaccination with VNUA-ASFV-LAVL3 elicited robust humoral and cellular immune responses in pigs, achieving 100% protection against a lethal wild-type ASFV (genotype II) challenge at all tested doses (103, 104, and 105 TCID50). Furthermore, a single vaccination (104 TCID50) provided protection for up to 2 months. These findings suggest that VNUA-ASFV-LAVL3 can be utilized as a promising safe and efficacious LAV candidate against the contemporary pandemic genotype II ASFV.

Long-term impact of rotavirus vaccination on all-cause and rotavirus-specific gastroenteritis and strain distribution in Central Kenya: An 11-year interrupted time-series analysis.

BACKGROUND: Kenya introduced a monovalent rotavirus vaccine administered orally at 6 and 10 weeks of age into her National Immunization Program in July 2014. The study evaluated the long-term impact of the vaccine on hospitalization for all-cause and rotavirus-specific acute gastroenteritis (AGE) and strain epidemiology in Kenya. METHODS: Data on all-cause and rotavirus-specific AGE and strain distribution were derived from an eleven-year hospital-based surveillance of AGE among children aged <5 years at Kiambu County Teaching and Referral Hospital (KCTRH) in Central Kenya between 2009 and 2020. Fecal samples were screened for group A rotavirus using ELISA and genotyped using multiplex semi-nested RT-PCR. Trends in all-cause and rotavirus-related AGE and strain distribution were compared between the pre-vaccine (July 2009-June 2014), early post-vaccine (July 2014-June 2016) and late post-vaccine (February 2019-October 2020) periods. RESULTS: Rotavirus-specific AGE was detected at 27.5% (429/1546, 95% CI: 25.5-30.1%) in the pre-vaccine period; 13.8% (91/658, 95% CI: 11.3-16.6%) in the early post-vaccine period (July 2014-June 2016); and 12.0% (229/1916, 95% CI: 10.6-13.5%) in the late post-vaccine period (February 2019-October 2020). This amounted to a decline of 49.8% (95% CI: 34.6%-63.7%) in rotavirus-specific AGE in the early post-vaccine period and 53.4% (95% CI: 41.5-70.3%) in the late post-vaccine period when compared to the pre-vaccine period. All-cause AGE hospitalizations declined by 40.2% (95% CI: 30.8%-50.2%) and 75.3% (95% CI: 65.9-83.1%) in the early post-vaccine and late post-vaccine periods, respectively, when compared to the pre-vaccine period. G3P [8] was the predominant strain in the late post-vaccine period, replacing G1P[8] which had predominated in the pre-vaccine and early post-vaccine periods. Additionally, we detected considerable proportions of uncommon strains G3P[6] (4.8%) and G12P[6] (3.5%) in the post-vaccine era. CONCLUSION: Rotavirus vaccination has resulted in a significant decline in all-cause and rotavirus-specific AGE, and thus, provides strong evidence for public health policy makers in Kenya to support the sustained use of the rotavirus vaccine in routine immunization. However, the shift in strain dominance and age distribution of rotavirus AGE in the post-vaccine era underscores the need for continued surveillance to assess any possible vaccine-induced selective pressure that could diminish the vaccine effectiveness over time.

Correlation between systemic allergen desensitisation and long-term asthma protection in mice following intravenous administration of the live tuberculosis vaccine MTBVAC.

BACKGROUND: MTBVAC is a live attenuated tuberculosis vaccine, currently undergoing phase III evaluation for tuberculosis prevention. In previous preclinical studies, we found that local pulmonary administration of MTBVAC via the intranasal route had a strong therapeutic effect against asthma. This effect correlated with the abrogation of allergen-specific Th2 response in the lungs. METHODS: Using different mouse models of asthma, we investigated the effect of MTBVAC administered by intravenous (IV) route and its potential as immunotherapeutic agent to induce desensitisation of allergen-specific responses at a systemic level. We explored the effects of this process in the efficacy against airway hyperresponsiveness (AHR) induced by exposure to different allergens. FINDINGS: IV MTBVAC was highly efficient at reducing AHR induced by different allergens. Additionally, IV MTBVAC was found to be well-tolerated, being progressively eliminated from the different organs analysed. From a mechanistic standpoint, we observed that MTBVAC intravenous, but not intranasal, impaired allergen-specific Th2 response in both lungs and spleen. This reduction at a systemic level correlated with long-term therapeutic protection against allergen exposure. Our results also revealed differential immunological mechanisms governing systemic and local pulmonary allergen desensitisation processes. Notably, in a cohort of patients with asthma sensitive to house dust mite (HDM), in vitro incubation of peripheral blood mononuclear cells (PBMCs) with MTBVAC prevented allergen-specific production of Th2 cytokines IL-4 and IL-5. INTERPRETATION: Altogether, our results suggest that intravenous MTBVAC could be a plausible allergen desensitising approach for treatment of asthma, and could provide long-term protection against allergen exposure. FUNDING: MCIN/AEI/10.13039/501100011033 [grants number RTI2018-097625-B-I00 and PID2022-138624OB-I00]; Consorcio Centro de Investigación Biomédica en Red- (Groups CB06/06/0020 and CB06/06/0013), Instituto de Salud Carlos III.

Generation and evaluation of Salmonella entericaserovar Choleraesuis mutant strains as a potential live-attenuated vaccine.

BACKGROUND: Salmonella entericaserovar Choleraesuis (S.C) is a swine enteric pathogen causing paratyphoid fever, enterocolitis, and septicemia in piglets. S. C is mainly transmitted through the fecal-oral route. Vaccination is an effective strategy for preventing and controlling Salmonella infection. RESULTS: Herein, we used CRISPR-Cas9 technology to knockout the virulence regulatory genes, rpoS, and slyA of S. C and constructed the ∆rpoS, ∆slyA, and ∆rpoS ∆slyA strains. The phenotypic characteristics of the mutant strains remained unchanged compared with the parental wild-type strain. In vivo study, unlike the wild-type strain, the ∆slyA and ∆rpoS ∆slyA strains alleviated splenomegaly, colon atrophy, and lower bacterial loads in the spleen, liver, ileum, and colon. These mutant strains survived in Peyer's patches (PPs) and mesenteric lymph nodes (MLN) for up to 15 days post-infection. Furthermore, the immunization of the ∆rpoS ∆slyA strain induced robust humoral and cellular immune responses. CONCLUSIONS: Consequently, vaccination with ∆rpoS ∆slyA conferred a high percentage of protection against lethal invasive Salmonella, specifically S. C, in mice. This study provided novel insights into the development of live-attenuated vaccines against the infection of S. C.