Oral delivery of foreign antigens by attenuated Salmonella: consequences of prior exposure to the vector strain

Attridge, Stephen R.; Davies, R.C.; LaBrooy, Justin T.

doi:10.1016/s0264-410x(96)00158-2

Cited by 47 publications

(31 citation statements)

References 17 publications

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“…This observation extends our previous findings in BALB/c mice (1,18) to hosts that might better reflect the responses of human vaccine recipients (5). This study therefore supports other recent data (18) indicating that vector priming could prejudice the use of recombinant Salmonella vaccines in regions where these bacteria may be endemic.…”

supporting

confidence: 91%

“…2A) and anti-LPS (Fig. 2B) responses comparable to those observed previously (1,18). Naïve animals displayed strong, consistent immunoglobulin G (IgG) responses to K88, with comparatively weak and delayed responses to vector LPS.…”

supporting

confidence: 77%

“…Two studies in which aroA Salmonella enterica serovar Dublin vectors were used failed to detect any reduction in responses to foreign antigen delivered orally or systemically to vector-primed hosts (2,19). Studies in three other laboratories employed aroA S. enterica serovar Typhimurium (11,14) or the naturally attenuated S. enterica serovar Stanley (1,18) as vectors and concluded that prior exposure to the vector significantly compromises both serum and intestinal antibody responses to a range of foreign antigens. The factors that determine the impact of vector priming remain unclear but include the nature of the foreign antigen and the Salmonella vector (18).…”

mentioning

confidence: 99%

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Vector Priming Reduces the Immunogenicity ofSalmonella-Based Vaccines inNramp1^+/+Mice

Vindurampulle

Attridge

2003

Infect Immun

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The present studies in Nramp1 ؊/؊ BALB/c and Nramp1 ؉/؉ CBA mice question the significance of this genotype as a determinant of the level of gut colonization following oral administration of naturally attenuated or highly virulent Salmonella strains. In line with previous results in BALB/c hosts, vector priming of CBA mice with Salmonella enterica serovar Stanley was found to significantly compromise the immunogenicity of a recombinant construct expressing a foreign pilus protein.

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supporting

confidence: 91%

supporting

confidence: 77%

mentioning

confidence: 99%

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Vector Priming Reduces the Immunogenicity ofSalmonella-Based Vaccines inNramp1^+/+Mice

Vindurampulle

Attridge

2003

Infect Immun

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“…However, only recently has consideration been given to the effects of prior exposure to the vector strain on the efficacy of such vaccines. Data from our laboratory were the first to indicate that prior exposure to Salmonella can dramatically reduce serum antibody responses to a foreign antigen subsequently delivered by the same strain (1). However, this finding contradicted the original study of Bao and Clements (2), who reported that prior exposure to Salmonella of a homologous or heterologous serotype enhanced antibody responses to a foreign antigen delivered orally by Salmonella.…”

mentioning

confidence: 63%

Impact of Vector Priming on the Immunogenicity of RecombinantSalmonellaVaccines

Vindurampulle

Attridge

2003

Infect Immun

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There are conflicting reports concerning the impact of prior vector priming on the immunogenicity of recombinant-Salmonella-based vaccines. A comparison of experimental protocols identified two variables which might account for this inconsistency: the potential of the vector strain to colonize the murine gut-associated lymphoid tissue (GALT) and the nature of the foreign antigen subsequently delivered by the recombinant Salmonella construct. The former was investigated by constructing an aroA mutant of the Salmonella enterica serovar Stanley vector previously used in our laboratory. Although the introduction of an aroA mutation had surprisingly little effect on GALT colonization, it did reduce the strength of antilipopolysaccharide (anti-LPS) antibody responses and the impact of vector priming. Studies were also performed to ascertain the extent to which any observed hyporesponsiveness consequent upon vector priming might be determined by the characteristics of the foreign antigen. S. enterica serovar Stanley was used to deliver either of two Escherichia coli antigens, K88 pilus protein or the LT-B toxin subunit, to vector-primed mice. Both serum immunoglobulin G (IgG) and intestinal IgA responses to K88 were completely abolished, and those to LT-B were significantly reduced, as a consequence of vector priming. When similar experiments were performed with an aroA S. enterica serovar Dublin vector, responses to K88 were significantly reduced but those to LT-B were unaffected by vector priming. Paradoxically, a priming infection with this vector induced stronger anti-LPS antibody responses but was less likely to elicit a state of hyporesponsiveness to subsequently presented foreign antigen. The impact of vector priming thus depends on both the Salmonella strain used and the nature of the foreign antigen, but our present data strengthen concerns that preexisting antivector immunity represents a serious threat to the Salmonella-based vaccine strategy.

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“…Heterologous Ag delivery by Salmonella used to be largely dependent upon antibiotic selectable genes (37,38) or by alternative methods, including nonantibiotic-based vectors (39), balanced lethal stabilization systems (20,40), or by chromosomal insertions (41,42). Owing to the apparent drawbacks of stability and antibiotic gene leakage, the antibiotic-based vector delivery systems cannot be further developed for human use.…”

Section: Discussionmentioning

confidence: 99%

Oral Vaccination withSalmonellaSimultaneously ExpressingYersinia pestisF1 and V Antigens Protects against Bubonic and Pneumonic Plague

Yang

Hinnebusch

Trunkle

et al. 2007

The Journal of Immunology

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The gut provides a large area for immunization enabling the development of mucosal and systemic Ab responses. To test whether the protective Ags to Yersinia pestis can be orally delivered, the Y. pestis caf1 operon, encoding the F1-Ag and virulence Ag (V-Ag) were cloned into attenuated Salmonella vaccine vectors. F1-Ag expression was controlled under a promoter from the caf1 operon; two different promoters (P), PtetA in pV3, PphoP in pV4, as well as a chimera of the two in pV55 were tested. F1-Ag was amply expressed; the chimera in the pV55 showed the best V-Ag expression. Oral immunization with Salmonella-F1 elicited elevated secretory (S)-IgA and serum IgG titers, and Salmonella-V-Ag(pV55) elicited much greater S-IgA and serum IgG Ab titers than Salmonella-V-Ag(pV3) or Salmonella-V-Ag(pV4). Hence, a new Salmonella vaccine, Salmonella-(F1+V)Ags, made with a single plasmid containing the caf1 operon and the chimeric promoter for V-Ag allowed the simultaneous expression of F1 capsule and V-Ag. Salmonella-(F1+V)Ags elicited elevated Ab titers similar to their monotypic derivatives. For bubonic plague, mice dosed with Salmonella-(F1+V)Ags and Salmonella-F1-Ag showed similar efficacy (>83% survival) against ∼1000 LD50 Y. pestis. For pneumonic plague, immunized mice required immunity to both F1- and V-Ags because the mice vaccinated with Salmonella-(F1+V)Ags protected against 100 LD50 Y. pestis. These results show that a single Salmonella vaccine can deliver both F1- and V-Ags to effect both systemic and mucosal immune protection against Y. pestis.

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Oral delivery of foreign antigens by attenuated Salmonella: consequences of prior exposure to the vector strain

Cited by 47 publications

References 17 publications

Vector Priming Reduces the Immunogenicity ofSalmonella-Based Vaccines inNramp1^+/+Mice

Vector Priming Reduces the Immunogenicity ofSalmonella-Based Vaccines inNramp1^+/+Mice

Impact of Vector Priming on the Immunogenicity of RecombinantSalmonellaVaccines

Oral Vaccination withSalmonellaSimultaneously ExpressingYersinia pestisF1 and V Antigens Protects against Bubonic and Pneumonic Plague

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Oral delivery of foreign antigens by attenuated Salmonella: consequences of prior exposure to the vector strain

Cited by 47 publications

References 17 publications

Vector Priming Reduces the Immunogenicity ofSalmonella-Based Vaccines inNramp1+/+Mice

Vector Priming Reduces the Immunogenicity ofSalmonella-Based Vaccines inNramp1+/+Mice

Impact of Vector Priming on the Immunogenicity of RecombinantSalmonellaVaccines

Oral Vaccination withSalmonellaSimultaneously ExpressingYersinia pestisF1 and V Antigens Protects against Bubonic and Pneumonic Plague

Contact Info

Product

Resources

About

Vector Priming Reduces the Immunogenicity ofSalmonella-Based Vaccines inNramp1^+/+Mice

Vector Priming Reduces the Immunogenicity ofSalmonella-Based Vaccines inNramp1^+/+Mice