Quantitative evaluation of the efficacy of non-replicating vaccines for controlling African swine fever in domestic pigs: a systematic review and meta-analysis

BackgroundThe African swine fever virus (ASFV), prevalent globally, causes high mortality and morbidity in domestic pigs. However, there is a lack of effective treatment or vaccines against ASFV infection despite the ongoing research in this field.MethodsIn this systematic review and meta-analysis, we conducted a quantitative evaluation of the efficacy of non-replicating vaccines against ASFV. The vaccine efficacy (VE) was analyzed based on three key disease outcomes: mortality, fever, and clinical symptoms after infection.ResultsThe search of relevant electronic databases yielded 23 studies for inclusion in the review. Vaccination with subunit vaccines significantly reduced mortality risk in vaccinated pigs compared to that in controls (p = 0.02), with a relative risk (RR) of 0.90 (95% CI: 0.83–0.98), indicating a VE of 10% (95% CI: 2–17). However, subunit vaccines did not substantially reduce the risk of fever and other clinical symptoms in vaccinated pigs, with a RR of 0.97 (95% CI: 0.93–1.01) for both outcomes. Moreover, inactivated vaccines did not provide any protection against mortality (RR = 1.01, 95% CI: 0.95–1.06) or other clinical signs (RR = 1.00, 95% CI: 1.00–1.00). No significant between-study heterogeneity was detected, indicating consistent findings across different vaccination trials. Thus, currently available non-replicating vaccines fail to deliver the protection required for field applications.ConclusionCurrently, subunit vaccines are more likely to serve as long-term options for vaccine development strategies. Further research is essential to deepen our understanding of the roles and significance of humoral and cellular immune responses against ASFV, and to identify critical viral antigens that can induce effective protective immunity

Effectiveness of F18+ fimbrial antigens released by a novel autolyzed Salmonella expression system as a vaccine candidate against lethal F18+ STEC infection

Porcine edema disease (ED) caused by Shiga toxin 2e producing Escherichia coli expressing F18ab+ fimbriae (F18ab+STEC) frequently occurs in post-weaned piglets, resulting in significant economic loss in swine industries worldwide. In the present study, we proposed an effective prevention scheme against ED in which the attenuated Salmonella Typhimurium inactivated by the E gene mediated cell lysis to deliver target antigens, FedF and FedA, which function in fimbrial-mediated adhesion and as a major subunit of F18ab+fimbriae, respectively. The co-expression of FedA and FedF protein with outermembrane protein A signal peptide was confirmed in the resultant strains JOL1460 and JOL1464 by immunoblot analysis. Immunization with the candidate strains in mice led to the significant generation of immunoglobulin (Ig) G, specific to both antigens and secretory IgA specific to FedF (P < 0.05). The titers of IgG isotypes, IgG1 and IgG2a, used as markers for T-helpers (Th)-2 and Th-1 lymphocytes, respectively, also significantly increased in the immunized group (P < 0.05). The increase in CD3+CD4+ T lymphocyte subpopulation and in vitro proliferative activity was observed in in vivo stimulated splenocytes, which indicated the immunostimulatory effect of the candidate strains. Moreover, the immunized mice were completely protected from a lethal challenge against wild-type F18+ETEC whereas 28% of mice died in the non-immunized group. This study demonstrated that the inactivated Salmonella system can efficiently express and release FedF and FedA and induce robust immune responses specific to the target antigens, which is sufficient to protect the mice from the lethal challenge

Potent immune responses induced by a Salmonella ghost delivery system that expresses the recombinant Stx2eB, FedF, and FedA proteins of the Escherichia coli-producing F18 and Shiga toxin in a murine model and evaluation of its protective effect as a porcine vaccine candidate

Background: In the pathogenicity of porcine edema disease (ED), which is caused by the Escherichia coli-producing F18 and Shiga toxin, F18+ fimbrial adhesins and Shiga toxin 2e (Stx2e) play pivotal roles in the colonization and enterotoxicity of this pathogen. Objective: To develop a vaccine candidate against ED by combining three selected antigens of F18+ E. coli. Methods: Genetically engineered Salmonella Typhimurium (ST) ghosts that express Stx2eB, FedF, and FedA were individually inserted in a ghost plasmid cassette, and the resultant plasmids were transformed into an attenuated ST (JOL912). The individual expression of Stx2eB, FedF, and FedA in JOL912 was validated by using an immunoblotting assay. Results: Immunization of the ghosts in BALB/c mice led to a significant increase in antigen-specific secretory IgA and serum IgG. Significantly marked elevation of the CD3+CD4+ T cell subpopulation and lymphocyte proliferating activity in the primed splenocytes were also observed. Furthermore, mRNA of IL-4 and IFN-γ were highly upregulated in in vitro stimulated splenic T cells. Subsequently, the immunized mice showed significant protection efficacy against a lethal dose 50 of a virulent strain, resulting in approximately 85% and 92% survival rates in mice with a single- and double-dose immunization, respectively, compared to only 40% of the non-immunized controls. Conclusion: A mixture of the ghosts expressing these three antigens is a potential vaccine candidate for protection against the porcine edema disease

Antigenic and functional profiles of a Lawsonia intracellularis protein that shows a flagellin-like trait and its immuno-stimulatory assessment

Abstract The obligate intracellular Lawsonia intracellularis (LI), the etiological agent of proliferative enteropathy (PE), is an economically important disease in the swine industry. Due to extreme difficulty of in vitro culture of the pathogen, molecular characterization of protein components of LI that are targets of the immune system, is difficult; thus, the scientific evidence to drive the development of preventive measures is lacking. In this work, we investigated the antigenic and functional characteristics of a putative flagellar-associated protein, LI0570, using in silico computational approaches for epitope prediction and an in vitro protein-based molecular assay. The amino acid sequence of LI0570 exhibited similarities to flagellar-associated proteins in four different bacterial strains. The presence of B cell linear confirmative epitopes of the protein predicted by a bioinformatics tool was validated by western blot analysis using anti-LI mouse hyperimmune serum, which implied that LI0570 induced production of antigen-specific antibodies in vivo. Further, TLR5-stimulating activity and IL-8 cytokine expression produced via downstream signaling were observed in HEK-Blue™-hTLR5 cells stimulated with LI0570. This result indicates that the LI0570 protein can trigger an innate immune response followed by a T-cell-related adaptive immune response in an infected host. Collectively, the data presented here support that the LI0570 protein which shows the antigenic potential could be a useful component of a recombinant vaccine against PE, providing progress toward an effective prevention strategy

Salmonella Typhimurium, the major causative agent of foodborne illness inactivated by a phage lysis system provides effective protection against lethal challenge by induction of robust cell-mediated immune responses and activation of dendritic cells

International audienceAbstractSalmonella Typhimurium infection via foodborne transmission remains a major public health threat even in developed countries. Vaccines have been developed to reduce the disease burden at the pre-harvest stage, but the cell-mediated immune response against intracellular invasion of the pathogen is not sufficiently elicited by conventional killed Salmonella vaccines, which are safer than live vaccines. In this study, we developed a genetically inactivated vaccine candidate by introducing lysis plasmid pJHL454 harboring the λ phage holin–endolysin system into S. Typhimurium; we designated this vaccine JOL1950. In vitro expression of endolysin was validated by immunoblotting, and complete inactivation of JOL1950 cells was observed following 36 h of the lysis. Electron microscopic examinations by scanning electron microscopy and immunogold labeling transmission EM revealed conserved surface antigenic traits of the JOL1950 cells after lysis. An in vivo immunogenicity study in mice immunized with lysed cells showed significantly increased serum IgG, IgG1, and IgG2a levels. Further, we observed markedly increased in vitro cell proliferation and upregulation of Th1, Th2, and Th17 cytokines in the repulsed splenic T-cells of immunized mice. In dendritic cells (DCs) treated with lysed JOL1950, we observed a significant increase in dendritic cell activation, co-stimulatory molecule production, and levels of immunomodulatory cytokines. In addition, Th1 and Th17 cytokines were also released by naïve CD4+ T-cells pulsed with primed DCs. Lysed JOL1950 also protected against lethal challenge in immunized mice. Together, these results indicate that our vaccine candidate has great potential to induce cell-mediated immunity against S. Typhimurium by facilitating the activation of DCs

Evidence-Based Approaches for Determining Effective Target Antigens to Develop Vaccines against Post-Weaning Diarrhea Caused by Enterotoxigenic Escherichia coli in Pigs: A Systematic Review and Network Meta-Analysis

In this study, we conducted a meta-analysis (MA) and systematic review to evaluate the effectiveness of vaccines against post-weaning diarrhea (PWD), caused by enterotoxigenic Escherichia coli (ETEC), in piglets. A Bayesian network meta-analysis (NMA) was also performed to compare the effects of combining different target antigens on vaccine efficacy. Relevant electronic databases were searched using pre-specified search terms, and 17 studies were selected based on three outcomes: diarrhea, mortality, and average daily weight gain (ADWG). In pairwise MA, the vaccinated group showed a significant decrease in diarrhea (OR = 0.124 [0.056, 0.275]) and mortality (OR = 0.273 [0.165, 0.451]), and a significant increase in ADWG (SMD = 0.699 [0.107, 1.290]) compared with those in controls. Furthermore, NMA results showed that all vaccine groups, except for group D (LT enterotoxin), were effective against PWD. Rank probabilities indicated that the F4 + F18 + LT combination was the best regimen for preventing diarrhea (SUCRA score = 0.92) and mortality (SUCRA score = 0.89). NMA also demonstrated that, among the vaccine groups, those inducing simultaneous anti-adhesion and antitoxin immunity had the highest efficacy. Our results provide evidence-based information on the efficacy of vaccines in reducing PWD incidence in pigs and may serve as guidelines for antigen selection for commercial vaccine development in the future

Revealing antimicrobial resistance profile and associated factors of Vibrio vulnificus isolated from clinical, environmental, and seafood samples across Asia: a systematic review and meta-analysis

The escalating antimicrobial resistance (AMR) in highly virulent Vibrio vulnificus poses a significant public health concern in Asia. Profiling the antibiogram of this pathogen is crucial for revealing its complex AMR patterns and guiding the selection of appropriate medications. Although previous studies have provided valuable insights regarding V. vulnificus AMR, they are constrained by limited sample diversity, inconsistent methodologies, and insufficient regional data. Moreover, no systematic attempt has been made to synthesize V. vulnificus AMR data across various sources and regions in Asia. A systematic review and meta-analysis are thus conducted in this study to assess the current AMR status of V. vulnificus isolated from clinical, environmental, and seafood samples. By synthesizing data from 32 articles across 13 Asian countries, a broader antibiogram has been provided, covering 13 major antimicrobial groups against V. vulnificus. Subgroup and regression analyses were also performed using study-level and country-specific covariates to explore the associated risk factors. The findings revealed low AMR rates for tetracyclines (4.89 %), quinolones (1.85 %), nitrofurans (0.86 %), and phenicols (0.61 %), highlighting their potential as primary treatment options. Conversely, high AMR rates were detected for lincosamides (80.32 %), polypeptides (64.42 %), and glycopeptides (56.14 %), necessitating careful consideration for their clinical use. For study-level covariates, subgroup and meta-regression analyses revealed that variations in the type of antimicrobial (R2 = 26.5 %, p < 0.0001), country (R2 = 18.33 %, p < 0.0001), and pathogen source (R2 = 10.46 %, p = 0.0007) significantly contributed to between-study heterogeneity in the detected AMR rates across studies. Moreover, the analyses of country-specific covariates indicated that antimicrobial consumption (AMC) in healthcare systems (R2 = 29.3, p = 0.06) and the country's gross domestic product (GDP) (R2 = 28.59, p = 0.06) affected the variations in AMR rates across countries to some extent. Consideration of study-level and country-specific covariates is thus recommended for future research to effectively mitigate the threat of V. vulnificus AMR across Asia and reduce its pervasive impact on public health