Identification of Protective Antigens for Vaccination against Systemic Salmonellosis

Bumann, Dirk

doi:10.3389/fimmu.2014.00381

Cited by 19 publications

(11 citation statements)

References 51 publications

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“…The microorganism should be recognized by antibodies, e.g., in the gut lumen, to prevent pathogen entry and should be presented by infected cells to promote T cell-mediated elimination. Although precise criteria for the selection of candidate Ags to be included in anti-Salmonella vaccines have to be carefully defined, some key parameters have emerged experimentally (185). Among the many Ags expressed in infected host tissues, surface-associated or secreted ones displaying high levels of expression should be favored.…”

Section: Salmonella Antigens and Their Use In Vaccine Formulationsmentioning

confidence: 99%

Vaccination against Salmonella Infection: the Mucosal Way

Gayet¹,

Bioley²,

Rochereau³

et al. 2017

Microbiol Mol Biol Rev

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subspecies includes several serovars infecting both humans and other animals and leading to typhoid fever or gastroenteritis. The high prevalence of associated morbidity and mortality, together with an increased emergence of multidrug-resistant strains, is a current global health issue that has prompted the development of vaccination strategies that confer protection against most serovars. Currently available systemic vaccine approaches have major limitations, including a reduced effectiveness in young children and a lack of cross-protection among different strains. Having studied host-pathogen interactions, microbiologists and immunologists argue in favor of topical gastrointestinal administration for improvement in vaccine efficacy. Here, recent advances in this field are summarized, including mechanisms of bacterial uptake at the intestinal epithelium, the assessment of protective host immunity, and improved animal models that closely mimic infection in humans. The pros and cons of existing vaccines are presented, along with recent progress made with novel formulations. Finally, new candidate antigens and their relevance in the refined design of anti- vaccines are discussed, along with antigen vectorization strategies such as nanoparticles or secretory immunoglobulins, with a focus on potentiating mucosal vaccine efficacy.

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Section: Salmonella Antigens and Their Use In Vaccine Formulationsmentioning

confidence: 99%

Vaccination against Salmonella Infection: the Mucosal Way

Gayet¹,

Bioley²,

Rochereau³

et al. 2017

Microbiol Mol Biol Rev

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“…Rational vaccine development can be informed by detailed knowledge of antigen targeting in immune individuals (22). Indeed, understanding of antigen targeting in human and murine Salmonella infection has recently improved and sub-unit vaccine development for Salmonella has received greater attention (23–28).…”

Section: Introductionmentioning

confidence: 99%

Dual Immunization with SseB/Flagellin Provides Enhanced Protection against Salmonella Infection Mediated by Circulating Memory Cells

Lee

Benoun

Sheridan

et al. 2017

The Journal of Immunology

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The development of a sub-unit Salmonella vaccine has been hindered by the absence of detailed information about antigenic targets of protective Salmonella-specific T and B cells. Recent studies have identified SseB as a modestly protective antigen in susceptible C57BL/6 mice, but the mechanism of protective immunity remains undefined. Here, we report that simply combining Salmonella SseB with flagellin substantially enhances protective immunity, allowing immunized C57BL/6 mice to survive for up to 30 days following challenge with virulent bacteria. Surprisingly, the enhancing effect of flagellin did not require flagellin antigen targeting during secondary responses or recognition of flagellin by TLR5. While co-immunization with flagellin did not affect SseB-specific antibody responses, it modestly boosted CD4 responses. In addition, protective immunity was effectively transferred in circulation to parabionts of immunized mice, demonstrating that tissue resident memory is not required for vaccine-induced protection. Finally, protective immunity required host expression of IFN-γR but was independent of iNOS expression. Taken together, these data indicate that Salmonella flagellin has unique adjuvant properties that improve SseB-mediated protective immunity provided by circulating memory.

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“…There are 50-200 promising protective antigens amongst the .4000 proteins encoded in Salmonella genomes; suitable protective antigens need to be surface-exposed to enable antibody binding, which substantially narrows down the number of potential candidates (Bumann, 2014). In recent years, an increasing number of studies have demonstrated the effectiveness of membrane-anchored flagellin as a mucosal adjuvant, as well as its ability to promote cytokine expression by innate immune cells and trigger the generalized recruitment of T-and B-lymphocytes to secondary lymphoid organs (Mizel & Bates, 2010).…”

Section: Discussionmentioning

confidence: 99%

“…In sub-Saharan Africa, high-risk hosts of NTS include young children and human immunodeficiency virus-infected individuals, and case fatality rates in both groups are~20-25 % (MacLennan & Levine, 2013). As systemic salmonellosis has become increasingly difficult to treat with antibiotics due to rising resistance to fluoroquinolones and cephalosporins, prevention with vaccines is hampered by only moderate levels and limited duration of protection (Bumann, 2014). However, no licensed vaccines against human NTS infections have yet been developed.…”

Section: Introductionmentioning

confidence: 99%

Mouse models for assessing the cross-protective efficacy of oral non-typhoidal Salmonella vaccine candidates harbouring in-frame deletions of the ATP-dependent protease lon and other genes

Matsui

Fukiya

Kodama-Akaboshi

et al. 2015

Journal of Medical Microbiology

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In BALB/c mouse models of Salmonella enterica serovar Typhimurium infection, a single oral immunization with a mutant strain with an insertion of the chloramphenicol resistance gene into the ATP-dependent protease clpP or lon gene decreased the number of salmonellae in each tissue sample 5 days after oral challenge with virulent S. Typhimurium at weeks 26 and 54 postimmunization. These data suggested that an oral immunization with the ClpP-or Lon-disrupted S. Typhimurium strain could provide long-term protection against oral challenge with virulent S. Typhimurium. Accordingly, recombinant oral non-typhoidal Salmonella (NTS) vaccines were constructed by incorporating mutants of both S. Typhimurium and S. enterica serovar Enteritidis harbouring stable in-frame markerless deletions of the clpP-lon-sulA (suppressor of lon), lonsulA or lon-msbB (acyltransferase) genes. Amongst these orally administered vaccine candidates, those with the lon-sulA gene deletion mutants of S. Typhimurium and S. Enteritidis protected BALB/c and C57BL/6J mice against oral challenge with both virulent S. Typhimurium and virulent S. Enteritidis. Therefore, the in-frame markerless lon-sulA gene deletion mutant of S. Typhimurium or S. Enteritidis could be a promising cross-protective NTS live vaccine candidate for practical use in humans.

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Identification of Protective Antigens for Vaccination against Systemic Salmonellosis

Cited by 19 publications

References 51 publications

Vaccination against Salmonella Infection: the Mucosal Way

Vaccination against Salmonella Infection: the Mucosal Way

Dual Immunization with SseB/Flagellin Provides Enhanced Protection against Salmonella Infection Mediated by Circulating Memory Cells

Mouse models for assessing the cross-protective efficacy of oral non-typhoidal Salmonella vaccine candidates harbouring in-frame deletions of the ATP-dependent protease lon and other genes

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