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Background. We examined the association between Helicobacter pylori infection and the immune response following oral immunization of US adults with attenuated Salmonella Typhi vaccine CVD 908-htrA. Methods. Baseline sera from 74 volunteers without a history of typhoid fever who were immunized orally with CVD 908-htrA were tested by enzyme-linked immunosorbent assay for immunoglobin G (IgG) antibodies to H. pylori, hepatitis A antibodies (a marker of low socioeconomic status and exposure to enteric infections), and pepsinogen (PG) I and II levels (measures of gastric inflammation). IgG against S. Typhi lipopolysaccharide (LPS) O and flagella was measured before and 28 days following immunization; a ≥4-fold increase in titer from baseline constituted seroconversion. Results. Seroconversion of S. Typhi IgG LPS antibodies was significantly higher among vaccinees infected with H. pylori versus uninfected subjects: adjusted odds ratio (OR) 3.8, 95% confidence interval (CI), 1.1-12.6 (P = .03). A low PG I: PG II ratio (<5), indicating more advanced corpus gastritis, increased the odds of seroconversion of IgG S. Typhi flagella antibody (adjusted OR 6.4, 95% CI, 1.3-31.4; P = .02). Hepatitis A infection did not influence the immune response to CVD 908-htrA. Conclusions. H. pylori infection and gastric inflammation may enhance humoral immunity to oral attenuated S. Typhi vaccine.

Orally administered recombinant Salmonella vaccines represent an attractive option for mass vaccination programmes against various infectious diseases. Therefore, it is crucial to gather knowledge about the possible impact of preexisiting immunity to carrier antigens on the immunogenicity of recombinant vaccines. Thirteen volunteers were preimmunized with Salmonella typhi Ty21a in order to evaluate the effects of prior immunization with the carrier strain. Then, they received three doses of 1–2×10 10 viable organisms of either the vaccine strain S. typhi Ty21a (pDB1) expressing subunits A and B of recombinant Helicobacter pylori urease ( n=9), or placebo strain S. typhi Ty21a ( n=4). Four volunteers were preimmunized and boosted with the vaccine strain S. typhi Ty21a (pDB1). No serious adverse effects were observed in any of the volunteers. Whereas none of the volunteers primed and boosted with the vaccine strain responded to the recombinant antigen, five of the nine volunteers preimmunized with the carrier strain showed cellular immune responses to H. pylori urease (56%). This supports the results of a previous study in non-preimmunized volunteers where 56% (five of nine) of the volunteers showed a cellular immune response to urease after immunisation with S. typhi Ty21a (pDB1).

Salmonella enterica serovar Typhi produces significant morbidity and mortality worldwide despite the fact that there are licensed Salmonella Typhi vaccines available. This is primarily due to the fact that these vaccines are not used in the countries that most need them. There is growing recognition that an effective invasive Salmonella vaccine formulation must also prevent infection due to other Salmonella serovars. We anticipate that a multivalent vaccine that targets the following serovars will be needed to control invasive Salmonella infections worldwide: Salmonella Typhi, Salmonella Paratyphi A, Salmonella Paratyphi B (currently uncommon but may become dominant again), Salmonella Typhimurium, Salmonella Enteritidis and Salmonella Choleraesuis (as well as other Group C Salmonella). Live attenuated vaccines are an attractive vaccine formulation for use in developing as well as developed countries. Here, we describe the methods of attenuation that have been used to date to create live attenuated Salmonella vaccines and provide an update on the progress that has been made on these vaccines.

Invasive non-typhoidal Salmonella (iNTS) disease is an under-recognized high-burden disease causing major health and socioeconomic issues in sub-Saharan Africa (sSA), predominantly among immune-naïve infants and young children, including those with recognized comorbidities such as HIV infection. iNTS disease is primarily caused by Salmonella enterica serovar Typhimurium sequence type (ST) 313 and ‘African-restricted clades’ of Salmonella Enteritidis ST11 that have emerged across the African continent as a series of epidemics associated with acquisition of new antimicrobial resistance. Due to genotypes with a high prevalence of antimicrobial resistance and scarcity of therapeutic options, these NTS serovars are designated by the World Health Organization as a priority pathogen for research and development of interventions, including vaccines, to address and reduce NTS associated bacteremia and meningitis in sSA. Novel and traditional vaccine technologies are being applied to develop vaccines against iNTS disease, and the results of the first clinical trials in the infant target population should become available in the near future. The “Vaccine Value Profile” (VVP) addresses information related predominantly to invasive disease caused by Salmonella Enteritidis and Salmonella Typhimurium prevalent in sSA. Information is included on stand-alone iNTS disease candidate vaccines and candidate vaccines targeting iNTS disease combined with another invasive serotype, Salmonella Typhi, that is also common across sSA. Out of scope for the first version of this VVP is a wider discussion on either diarrheagenic NTS disease (dNTS) also associated with Salmonella Enteritidis and Salmonella Typhimurium or the development of a multivalent Salmonella vaccines targeting key serovars for use globally. This VVP for vaccines to prevent iNTS disease is intended to provide a high-level, holistic assessment of the information and data that are currently available to inform the potential public health, economic, and societal value of pipeline vaccines and vaccine-like products. Future versions of this VVP will be updated to reflect ongoing activities such as vaccine development strategies and a “Full Vaccine Value Assessment” that will inform the value proposition of an iNTS disease vaccine. This VVP was developed by a working group of subject matter experts from academia, non-profit organizations, public private partnerships, and multi-lateral organizations, and in collaboration with stakeholders from the World Health Organization African Region. All contributors have extensive expertise on various elements of the iNTS disease VVP and collectively aimed to identify current research and knowledge gaps. The VVP was developed using only existing and publicly available information.

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. •Three mutant Salmonella entericaserovar Choleraesuis (S. C) strains ∆rpoS, ∆slyA, and ∆rpoS ∆slyA were generated.•The mutant S.C. strains remained similar phenotypes with the parental strain but with much lower virulence.•The ∆rpoS ∆slyAS.C strain showed ideal immunity and protective efficacy.

Invasive nontyphoidal Salmonella (iNTS) infections, primarily caused by Salmonella enterica serovars Typhimurium (S. Typhimurium) and Enteritidis (S. Enteritidis), represent a significant public health concern, particularly in sub-Saharan Africa, where multidrug-resistant (MDR) strains are increasingly prevalent. Despite the substantial disease burden, no vaccines are currently licensed for iNTS. This study aimed to develop an iNTS conjugate vaccine by conjugating O-specific polysaccharide (OSP) antigens to carrier proteins using chemical conjugation, a proven method known for its efficiency and scalability in licensed glycoconjugate vaccines. Various carrier proteins and chemical conjugation processes were evaluated to optimize the iNTS OSP conjugate vaccine candidates. Through this optimization, diphtheria toxoid (DT) was identified as the carrier protein that significantly enhances the anti-OSP immunogenicity of the iNTS conjugates. Key properties, such as the molecular weight and OSP:DT ratio in the iNTS OSP conjugate were found to be controllable by adjusting the ratios of CDAP conjugate reagent and DT to iNTS OSP. Optimal conjugation process parameters were identified by evaluating the relationship between these property and immunogenicity through tests in mice. The optimized iNTS conjugates for S. Typhimurium and S. Enteritidis were further developed into a bivalent formulation. This formulation was selected based on a dose-dependent immunogenicity study and included alum as an adjuvant to enhance immune response. Ultimately, a trivalent drug product formulation was developed by combining the bivalent iNTS conjugate vaccine with a typhoid conjugate vaccine. Our findings demonstrated that the iNTS OSP-DT conjugates, at the optimal conjugation ratios, induced robust immune responses with high anti-OSP IgG titers for both iNTS serovars, comparable to or exceeding those of other formulations. The inclusion of alum further enhanced immunogenicity across all formulations. Notably, the trivalent vaccine formulation showed promising results, maintaining robust immunogenic responses against all iNTS OSP antigens and the Vi polysaccharide antigen of Salmonella Typhi, without compromising the immunogenicity of any individual antigens. This study suggests that a bivalent iNTS vaccine combined with a typhoid conjugate vaccine could provide broad protection against both iNTS infections and typhoid fever, addressing a critical unmet need in regions with limited resources.

Background Salmonella infections represent a major global public health concern due to their widespread zoonotic transmission, antimicrobial resistance, and associated morbidity and mortality. This review aimed to summarize the zoonotic nature of Salmonella , the challenges posed by antimicrobial resistance, the global burden of infections, and the need for effective vaccination strategies to mitigate the rising threat of Salmonella . Methods A systematic review of literature was conducted using databases such as PubMed, Scopus, Web of Science, and Google Scholar. Relevant studies published in English were identified using keywords including Salmonella , vaccination, antimicrobial resistance, and public health. Articles focusing on epidemiology, vaccine development, and strategies to control Salmonella infections were included, while conference abstracts and non-peer-reviewed studies were excluded. Results Salmonella infections result in approximately 95 million global cases annually, with an estimated 150,000 deaths. Regional variations were evident, with higher infection rates in low- and middle-income countries due to poor sanitation and food safety standards. Salmonella Enteritidis and S. Typhimurium were the most prevalent serovars associated with human infections. The review highlighted an alarming rise in multidrug-resistant (MDR) Salmonella strains, particularly due to the overuse of antibiotics in humans and livestock. Despite progress in vaccine development, challenges remain in achieving a universal vaccine that targets diverse Salmonella serovars. Live-attenuated, killed, recombinant, subunit, and conjugate vaccines are currently under development, but limitations such as efficacy, cost, and accessibility persist. Conclusions Salmonella infections continue to impose a significant burden on global health, exacerbated by rising antimicrobial resistance. There is an urgent need for a multifaceted approach, including improved sanitation, prudent antibiotic use, and the development of affordable, broad-spectrum vaccines. Strengthening surveillance systems and promoting collaborative global efforts are essential to effectively control and reduce the burden of Salmonella .

Fowl typhoid is a significant avian disease worldwide affecting mainly chickens, turkeys and other bird species, such as partridges. In Morocco, the disease causes a high mortality rate in farmed partridges. Vaccination of partridges is a priority to preserve the breed however; the vaccine has never been evaluated in this species. The study was conducted to assess safety and efficacy of a locally produced Salmonella 9R live vaccine in partridges. Groups of vaccinated partridges received the vaccine at 6 weeks of age, followed by a second injection 6 weeks after. The challenge test was performed at 14 weeks with Salmonella gallinarum MSG1 virulent strain. The challenge demonstrated 65 % protection in vaccinated challenged partridges, with a reduction in organ invasion compared to unvaccinated control birds, which exhibited 70,6 % mortality. The live attenuated 9R vaccine, could be safely used to reduce flock losses and contribute to the reduction of infection.

Gamma-irradiated inactivated bacterial vaccines have emerged as a safer alternative, overcoming the safety and immunogenicity limitations of conventional live attenuated and inactivated vaccines. This study aimed to develop gamma-irradiated Salmonella Gallinarum (γ-SG) vaccine from a local field strain and evaluate its cell-mediated immune response in a chicken model, focusing on CD4+ and CD8+ T cell activation and IFN-γ production. Radiation doses ranging from 1.5 to 10 kGy were evaluated to determine the optimal level for inactivating bacterial replication while retaining metabolic activity. Dose of 7 kGy effectively inhibited replication while maintaining residual metabolic activity. In an immunization-challenge study, commercial broiler chickens (Ross 308) at 14 days of age were vaccinated twice at two-week intervals orally with γ-SG (γ-SG Oral), intramuscularly with oil-based γ-SG (γ-SG IM), oil-based formalin-inactivated SG (F-SG) and SG 9R vaccines with the concentration of each 2 × 108 CFU and SG 9R at the concentration of 2 × 107 CFU in 0.2 mL PBS. Our study showed that chickens vaccinated with γ-SG (Oral) exhibited significantly higher CD4+ T cell response (39.74 %) when compared with SG 9R (29.36 %), γ-SG (IM) (20.2 %) and F-SG (22.8 %) groups at three weeks post-vaccination (WPV). Similarly, CD8+ T cell response was highest in γ-SG (Oral) group (28.6 %) versus SG 9R (5.28 %), γ-SG (IM) (19.7 %), and F-SG (14.3 %) at 3WPV. IFN-γ concentrations were also significantly elevated in γ-SG (Oral) group (452.75 pg/mL) when compared with SG 9R (307.5 pg/mL), γ-SG (IM) (334 pg/mL), and F-SG (221.75 pg/mL) groups. In vivo efficacy study showed that γ-SG (Oral) provided 100 % protection with 0 % mortality, comparable to SG 9R while F-SG and γ-SG (IM) groups showed 40 % and 20 % mortality, respectively, compared to 70 % in unvaccinated chickens challenged with wild-type SG. These findings demonstrate that non-adjuvanted oral γ-SG vaccination is an effective strategy against fowl typhoid.

Invasive nontyphoidal Salmonella disease (iNTS) is a leading cause of death and morbidity in Africa. The most common pathogens are Salmonella enterica serovars Typhimurium and Enteritidis. The O-antigen portion of their lipopolysaccharide is a target of protective immunity and vaccines targeting O-antigen are currently in development. Here we investigate the use of Generalized Modules for Membrane Antigens (GMMA) as delivery system for S. Typhimurium and S. Enteritidis O-antigen. Gram-negative bacteria naturally shed outer membrane in a blebbing process. By deletion of the tolR gene, the level of shedding was greatly enhanced. Further genetic modifications were introduced into the GMMA-producing strains in order to reduce reactogenicity, by detoxifying the lipid A moiety of lipopolysaccharide. We found that genetic mutations can impact on expression of O-antigen chains. All S. Enteritidis GMMA characterized had an O-antigen to protein w/w ratio higher than 0.6, while the ratio was 0.7 for S. Typhimurium ΔtolR GMMA, but decreased to less than 0.1 when further mutations for lipid A detoxification were introduced. Changes were also observed in O-antigen chain length and level and/or position of O-acetylation. When tested in mice, the GMMA induced high levels of anti-O-antigen-specific IgG functional antibodies, despite variation in density and O-antigen structural modifications. In conclusion, simplicity of manufacturing process and low costs of production, coupled with encouraging immunogenicity data, make GMMA an attractive strategy to further investigate for the development of a vaccine against iNTS.