Constitutive Expression of the Vi Polysaccharide Capsular Antigen in Attenuated<i>Salmonella enterica</i>Serovar Typhi Oral Vaccine Strain CVD 909

Wang, Jin Yuan; Noriega, Fernando; Galen, James E.; Barry, Eileen M.; Levine, Myron M.

doi:10.1128/iai.68.8.4647-4652.2000

Cited by 59 publications

(35 citation statements)

References 57 publications

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“…P ompC is supposedly active early during infection but is rather ineffective for humoral immune responses (4). Finally, the artificial P tac was used as a non-IVI reference promoter, since it is a commonly used promoter for constitutive expression in recombinant Salmonella (14,22,43,48,51). Moreover, antigen expression from P tac has been successfully used to induce specific CD4 ϩ T-cell responses in a tgTCR mouse model (see below) following oral immunization with recombinant Salmonella cells (5).…”

Section: Resultsmentioning

confidence: 99%

Regulated Antigen Expression in Live RecombinantSalmonella entericaSerovar Typhimurium Strongly Affects Colonization Capabilities and Specific CD4⁺-T-Cell Responses

Bumann

2001

Infect Immun

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Regulated antigen expression can influence the immunogenicity of live recombinant Salmonella vaccines, but a rational optimization has remained difficult since important aspects of this effect are incompletely understood. Here, attenuated Salmonella enterica serovar Typhimurium SL3261 strains expressing the model antigen GFP_OVA were used to quantify in vivo antigen levels by flow cytometry and to simultaneously follow the crucial early steps of antigen-specific T-cell responses in mice that are transgenic for a T-cell receptor recognizing ovalbumin. Among seven tested promoters, P pagC has the highest activity in murine tissues combined with low in vitro expression, whereas P tac has a comparable in vivo and a very high in vitro activity. Both SL3261 (pP pagC GFP_OVA) and SL3261 (pP tac GFP_OVA) cells can induce potent ovalbumin-specific cellular immune responses following oral administration, but doses almost 1,000-fold lower are sufficient for the in vivo-inducible construct SL3261 (pP pagC GFP_OVA) compared to SL3261 (pP tac GFP_OVA). This efficacy difference is largely explained by impaired early colonization capabilities of SL3261 (pP tac GFP_OVA) cells. Based on the findings of this study, appropriate in vivo expression levels for any given antigen can be rationally selected from the increasing set of promoters with defined properties. This will allow the improvement of recombinant Salmonella vaccines against a wide range of pathogens.

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Section: Resultsmentioning

confidence: 99%

Regulated Antigen Expression in Live RecombinantSalmonella entericaSerovar Typhimurium Strongly Affects Colonization Capabilities and Specific CD4⁺-T-Cell Responses

Bumann

2001

Infect Immun

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“…These vaccines will not provide protection against other Salmonella serovars, such as Salmonella serovar Paratyphi and nontyphoidal group D salmonellae, which may thus emerge as important causes of systemic salmonellosis. Furthermore, live oral typhoid vaccines which constitutively express Vi are also being developed and may have similar effects (29). Vi-negative Salmonella serovar Typhi can become clinically important only if the capsule is not essential for pathogenesis or transmission.…”

Section: Discussionmentioning

confidence: 99%

Vi Antigen Expression in Salmonella enterica Serovar Typhi Clinical Isolates from Pakistan

et al. 2005

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The accurate identification of Salmonella enterica subsp. enterica serovar Typhi variants that fail to express the capsular polysaccharide, Vi, is an important and much discussed issue for medical microbiology. We have tested a multiplex PCR method which shows the presence or absence of the genetic locus required for Vi expression. Of 2,222 Salmonella serovar Typhi clinical isolates collected from patients' blood over a 4-year period in a region of Pakistan where typhoid is endemic, 12 tested negative for Vi expression by serological agglutination. However, only 1 of these 12 was Vi negative by the multiplex PCR method. This result was confirmed by immunofluorescence, the most sensitive method for Vi characterization in Salmonella serovar Typhi. The multiplex PCR described therefore represents a simple and accurate method for surveillance for Vi-negative variants of Salmonella serovar Typhi in Pakistan. Testing of clinical isolates of Salmonella serovar Typhi, before subculture, from other regions where Vi-negative Salmonella serovar Typhi has been described should be carried out so that the impact of vaccination with purified Vi antigen on the levels of Vi-negative Salmonella serovar Typhi in bacterial populations can be assessed.

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“…This lack of Vi responsiveness could be the result of low expression of the Vi capsule, which is likely to be down regulated in vivo once the bacteria gain their intracellular niche in the gut associated lymphoid tissue [21]. To render the Vi expression constitutive, promoter P tviA in serovar Typhi vaccine CVD 908-htrA was replaced with the constitutive promoter P tac , resulting in CVD 909, which expresses Vi even under high-osmolarity conditions [22]. Our hypothesis was that this might result in serum IgG and mucosal IgA Vi antibody responses in orally vaccinated subjects, thereby enhancing the protection against typhoid fever.…”

Section: Introductionmentioning

confidence: 99%

Cell-mediated immune responses in humans after immunization with one or two doses of oral live attenuated typhoid vaccine CVD 909

Wahid

Salerno-Gonçalves

Tacket

et al. 2007

Vaccine

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CVD 909 is a novel live attenuated S. Typhi oral vaccine candidate derived from strain CVD 908-htrA which constitutively expresses Vi. Herein we investigated whether the genetic manipulations involved in modifying CVD 908-htrA altered its ability to induce potent T-cell immune responses (CMI) after a single dose (5 subjects) and, in a separate trial, whether a second dose (8 subjects) further enhanced its immunogenicity. In these clinical trials we observed that CVD 909 immunization elicits a wide array of CMI, including cytotoxic T cells (CTL), IFN-γ, TNF-α and IL-10 (but not IL-2, IL-4 or IL-5) production, and proliferation to S. Typhi antigens. However, the administration of a second dose did not result in increases in CMI. These results suggest that the genetic manipulations to constitutively express Vi did not adversely affect the ability of CVD 909 to elicit a wide array of CMI responses. These observations add impetus for the continuing evaluation of CVD 909 as a typhoid vaccine candidate.

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Constitutive Expression of the Vi Polysaccharide Capsular Antigen in AttenuatedSalmonella entericaSerovar Typhi Oral Vaccine Strain CVD 909

Cited by 59 publications

References 57 publications

Regulated Antigen Expression in Live RecombinantSalmonella entericaSerovar Typhimurium Strongly Affects Colonization Capabilities and Specific CD4⁺-T-Cell Responses

Regulated Antigen Expression in Live RecombinantSalmonella entericaSerovar Typhimurium Strongly Affects Colonization Capabilities and Specific CD4⁺-T-Cell Responses

Vi Antigen Expression in Salmonella enterica Serovar Typhi Clinical Isolates from Pakistan

Cell-mediated immune responses in humans after immunization with one or two doses of oral live attenuated typhoid vaccine CVD 909

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Constitutive Expression of the Vi Polysaccharide Capsular Antigen in AttenuatedSalmonella entericaSerovar Typhi Oral Vaccine Strain CVD 909

Cited by 59 publications

References 57 publications

Regulated Antigen Expression in Live RecombinantSalmonella entericaSerovar Typhimurium Strongly Affects Colonization Capabilities and Specific CD4+-T-Cell Responses

Regulated Antigen Expression in Live RecombinantSalmonella entericaSerovar Typhimurium Strongly Affects Colonization Capabilities and Specific CD4+-T-Cell Responses

Vi Antigen Expression in Salmonella enterica Serovar Typhi Clinical Isolates from Pakistan

Cell-mediated immune responses in humans after immunization with one or two doses of oral live attenuated typhoid vaccine CVD 909

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Regulated Antigen Expression in Live RecombinantSalmonella entericaSerovar Typhimurium Strongly Affects Colonization Capabilities and Specific CD4⁺-T-Cell Responses

Regulated Antigen Expression in Live RecombinantSalmonella entericaSerovar Typhimurium Strongly Affects Colonization Capabilities and Specific CD4⁺-T-Cell Responses