vaccines for use in humans: present and future perspectives

Garmory, Helen S; Brown, Karen; Titball, Richard W.

doi:10.1016/s0168-6445(02)00113-4

Cited by 55 publications

(69 citation statements)

References 94 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…As Salmonella strains have been shown to be very effective in delivering heterologous antigens (22,38), cross-immunity may be further enhanced by the overexpression of protective antigens. Lack of cross-protective immunity between different serotypes is a major problem in enteric pathogens other than Salmonella; therefore, it is worth testing rfaH mutants as live vaccines against other pathogens belonging to the Enterobacteriaceae.…”

Section: Discussionmentioning

confidence: 99%

Down-Regulation of Key Virulence Factors Makes the Salmonella enterica Serovar Typhimurium rfaH Mutant a Promising Live-Attenuated Vaccine Candidate

et al. 2006

View full text Add to dashboard Cite

Mutants of Salmonella enterica serovar Typhimurium that lack the transcriptional regulator RfaH are efficient as live oral vaccines against salmonellosis in mice. We show that the attenuation of the vaccine candidate strain is associated with reduced net growth in epithelial and macrophage cells. In order to identify the relevant RfaH-dependent genes, the RfaH regulon was determined with S. enterica serovars Enteritidis and Typhimurium using whole-genome Salmonella microarrays. As well as impacting the expression of genes involved in lipopolysaccharide (LPS) core and O-antigen synthesis, the loss of RfaH results in a marked down-regulation of SPI-4 genes, the flagellum/chemotaxis system, and type III secretion system 1. However, a proportion of these effects could have been the indirect consequence of the altered expression of genes required for LPS biosynthesis. Direct and indirect effects of the rfaH mutation were dissociated by genome-wide transcriptional profiling of a structural deep-rough LPS mutant (waaG). We show that truncation of LPS itself is responsible for the decreased intracellular yield observed for ⌬rfaH strains. LPS mutants do not differ in replication ability; rather, they show increased susceptibility to antimicrobial peptides in the intracellular milieu. On the other hand, evidence that deletion of rfaH, as well as some other genes involved in LPS biosynthesis, results in enhanced invasion of various mammalian cells is shown. Exposure of common minor antigens in the absence of serovar-specific antigens might be responsible for the observed cross-reactive nature of the elicited immune response upon vaccination. Increased invasiveness of the Salmonella rfaH mutant into antigen-presenting cells, combined with increased intracellular killing and the potential for raising a crossprotective immune response, renders the rfaH mutant an ideal vaccine candidate.Salmonella enterica can cause various diseases in humans and a wide variety of farm animals. Currently available vaccines do not confer optimal protection against Salmonella infection, and so development of effective vaccines is still a high priority (for a recent review, see reference 22). Currently, over 2,500 serovariants of S. enterica have been distinguished, based on the high polymorphism of lipopolysaccharide (LPS) O antigens and flagellar antigens. Immune cross-protection between serovariants of S. enterica is limited, hindering development of an efficacious broad-spectrum Salmonella vaccine. Recently, we reported that an attenuated mutant of S. enterica serovar Typhimurium strain SL1344 that lacks the transcriptional regulator RfaH was capable of eliciting protection against subsequent challenge by wild-type Salmonella in the mouse model of typhoid fever (41). Furthermore, sera of vaccinated mice were shown to cross-react to not only the isogenic wild-type strain but also heterologous serovariants of S. enterica and even Salmonella bongori.Transcriptional antitermination is a conserved mechanism of gene regulation based on overcoming i...

show abstract

Section: Discussionmentioning

confidence: 99%

Down-Regulation of Key Virulence Factors Makes the Salmonella enterica Serovar Typhimurium rfaH Mutant a Promising Live-Attenuated Vaccine Candidate

et al. 2006

View full text Add to dashboard Cite

show abstract

“…Attenuated Salmonella enterica strains have been studied intensively as live carriers of heterologous vaccine antigens delivered by mucosal or parenteral routes (Brey et al 1991, Garmory et al 2002. Orally delivered, attenuated Salmonella strains induce both systemic and secretory immune responses against the carrier strain as well as the heterologous passenger antigen (Garmory et al 2002).…”

mentioning

confidence: 99%

“…Orally delivered, attenuated Salmonella strains induce both systemic and secretory immune responses against the carrier strain as well as the heterologous passenger antigen (Garmory et al 2002). Additionally, peptides, particularly those encoding B-cell epitopes, may be expressed by attenuated Salmonella strains as hybrid proteins following genetic fusion to bacterial proteins.…”

mentioning

confidence: 99%

Anti-flagellin antibody responses elicited in mice orally immunized with attenuated Salmonella enterica serovar Typhimurium vaccine strains

Massis

Braga

Sbrogio-Almeida

et al. 2008

Mem. Inst. Oswaldo Cruz

View full text Add to dashboard Cite

show abstract

“…The parenteral whole cell vaccines have been associated with fever and systemic reactions. Although licensed, it is considered unsuitable for mass immunization and no longer in use (Garmony et al 2002). The other licensed vaccines against Salmonella in use globally are Vi polysaccharide vaccine and Ty21a live attenuated vaccine (Cheminay & Hensel 2008).…”

Section: Introductionmentioning

confidence: 99%

Protection against experimental salmonellosis by recombinant 49 kDa OMP of Salmonella enterica serovar Typhi: biochemical aspects

Kaur

Jain

2013

Biologia

View full text Add to dashboard Cite

Typhoid fever is systemic illness caused by Salmonella enterica serovar Typhi (S. Typhi) in humans. Increasing multidrug resistant strains of S. Typhi and limited effect of available vaccines has necessitated exploring of new immunogens for protection against it. Earlier studies have shown that a crude preparation of outer membrane proteins (OMPs) of S. Typhi evokes strong immune response and induces a protective immunity against infection caused by diverse Gram-negative bacteria. In the present study we have evaluated the protective effect of a purified recombinant 49 kDa (r49kDa) OMP of S. Typhi alone or along with alum or complete Freund's adjuvant, against a challenge by S. Typhi (0.4 × 50% lethal dose) by biochemical estimation of serum enzymes and oxidative stress enzymes in Swiss albino mice. There was a decrease in activity of alanine aminotransferase by 14.28%, 38.09%, 23.80%; aspartate aminotransferase by 6.25%, 25%, 16.25%; lipid peroxidation by 4.34%, 18.84%, 11.59%; and catalase by 8%, 14%, 10%, respectively, whereas increase in activity of reduced glutathione by 33.33%, 61.11%, 44.44%; glutathione peroxidase by 7%, 16%, 10%; and glutathione reductase by 8%, 20%, 12%, respectively, as compared to control animals challenged with bacteria without pre-immunization. The results indicated that immunization of mice with r49kDa OMP alone or in combination with adjuvants protected and normalized the liver. It reduces the development of oxidative stress in mice against Salmonella infection and the risk of getting typhoid. These results represent an additional supplement to our earlier reported data on protective immunity evoked by this protein.

show abstract

vaccines for use in humans: present and future perspectives

Cited by 55 publications

References 94 publications

Down-Regulation of Key Virulence Factors Makes the Salmonella enterica Serovar Typhimurium rfaH Mutant a Promising Live-Attenuated Vaccine Candidate

Down-Regulation of Key Virulence Factors Makes the Salmonella enterica Serovar Typhimurium rfaH Mutant a Promising Live-Attenuated Vaccine Candidate

Anti-flagellin antibody responses elicited in mice orally immunized with attenuated Salmonella enterica serovar Typhimurium vaccine strains

Protection against experimental salmonellosis by recombinant 49 kDa OMP of Salmonella enterica serovar Typhi: biochemical aspects

Contact Info

Product

Resources

About