Recombinant Salmonella enterica serovar Typhi in a prime-boost strategy

Vindurampulle, Christofer J.; Cuberos, Lilian; Barry, Eileen M.; Pasetti, Marcela F.; Levine, Myron M.

doi:10.1016/j.vaccine.2004.03.025

Cited by 26 publications

(23 citation statements)

References 45 publications

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“…and i.m.). Heterologous prime/boost strategies recently have been shown to significantly improve the immunogenicity of both eukaryotic and prokaryotic foreign (7,24,49). The results of our study further support the efficacy of the heterologous prime/boost strategy, as we observed a drastic elevation of GFPuv-specific IgG responses after GFPuv protein boosting (Tables 2 and 3).…”

Section: Discussionsupporting

confidence: 85%

Use of mchI Encoding Immunity to the Antimicrobial Peptide Microcin H47 as a Plasmid Selection Marker in Attenuated Bacterial Live Vectors

et al. 2008

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Live attenuated bacterial strains expressing heterologous antigens represent an attractive vaccine development strategy. However, the use of drug resistance genes for the selection of expression plasmids introduced into live vectors poses theoretical health risks. Therefore, we developed a novel approach for plasmid selection based on immunity to the antimicrobial peptide microcin H47 (MccH47). Two expression plasmids encoding the reporter green fluorescent protein (GFPuv) were constructed; selection markers comprised either mchI, conferring immunity to MccH47 (pGEN222I), or bla (encoding ␤-lactamase), conferring conventional resistance to ampicillin (pGEN222). GFPuv-specific serum immunoglobulin G (IgG) antibody responses were analyzed in mice immunized intranasally either with Salmonella enterica serovar Typhi CVD 908-htrA or Shigella flexneri 2a CVD 1208S live vector and were boosted parenterally with purified GFPuv. Similar IgG antibody responses were observed for both pGEN222 and pGEN222I when either CVD 1208S or CVD 908-htrA(pGEN222I) was used as the carrier. Interestingly, CVD 908-htrA(pGEN222I) elicited a significantly higher IgG response than CVD 908-htrA(pGEN222). We also compared the priming potential of homologous priming either with CVD 908-htrA(pGEN222I) or CVD 1208S(pGEN222I) to heterologous priming first with CVD 908-htrA(pGEN222I) and then with CVD 1208S(pGEN222I) and vice versa. Immunization with two unrelated live vectors significantly enhanced the IgG responses compared to responses engendered by homologous CVD 908-htrA(pGEN222I) but not to those of CVD 1208S(pGEN222I). MccH47 offers an alternate system for plasmid selection in bacterial live vectors that greatly improves their clinical acceptability. Furthermore, the success of the heterologous priming strategy supports the feasibility of the future development of multivalent live vector-based immunization strategies against multiple human pathogens.

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Section: Discussionsupporting

confidence: 85%

Use of mchI Encoding Immunity to the Antimicrobial Peptide Microcin H47 as a Plasmid Selection Marker in Attenuated Bacterial Live Vectors

et al. 2008

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“…On the other hand, RASV immunization showed a stronger priming effect or memory response upon parenteral injection with protein than primary vaccination by s.c. injection with protein. Similar results for mice and humans also indicated that live attenuated S. enterica serovar Typhimurium-based vaccines trigger long-lasting humoral, mucosal, and cellular responses upon a boost vaccination with subunit protein without the need for repeated immunization (49). Such a RASV priming and parenteral boost strategy to induce robust antibody responses could be valuable in breeding flocks for which the target is to develop a higher maternally transferable antibody titer to protect young chicks.…”

Section: Discussionmentioning

confidence: 62%

Recombinant AttenuatedSalmonella entericaSerovar Typhimurium Expressing the Carboxy-Terminal Domain of Alpha Toxin fromClostridium perfringensInduces Protective Responses against Necrotic Enteritis in Chickens

Zekarias

Curtiss

2008

Clin Vaccine Immunol

104

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Clostridium perfringens-induced necrotic enteritis (NE) is a widespread disease in chickens that causes high mortality and reduced growth performance. Traditionally, NE was controlled by the routine application of antimicrobials in the feed, a practice that currently is unpopular. Consequently, there has been an increase in the occurrence of NE, and it has become a threat to the current objective of antimicrobial-free farming. The pathogenesis of NE is associated with the proliferation of C. perfringens in the small intestine and the secretion of large amounts of alpha toxin, the major virulence factor. Since there is no vaccine for NE, we have developed a candidate live oral recombinant attenuated Salmonella enterica serovar Typhimurium vaccine (RASV) that delivers a nontoxic fragment of alpha toxin. The 3 end of the plc gene, encoding the C-terminal domain of alpha toxin (PlcC), was cloned into plasmids that enable the expression and secretion of PlcC fused to a signal peptide. Plasmids were inserted into Salmonella enterica serovar Typhimurium host strain 8914, which has attenuating pabA and pabB deletion mutations. Three-day-old broiler chicks were orally immunized with 10 9 CFU of the vaccine strain and developed alpha toxin-neutralizing serum antibodies. When serum from these chickens was added into C. perfringens broth cultures, bacterial growth was suppressed. In addition, immunofluorescent microscopy showed that serum antibodies bind to the bacterial surface. The immunoglobulin G (IgG) and IgA titers in RASV-immunized chickens were low; however, when the chickens were given a parenteral boost injection with a purified recombinant PlcC protein (rPlcC), the RASV-immunized chickens mounted rapid high serum IgG and bile IgA titers exceeding those primed by rPlcC injection. RASV-immunized chickens had reduced intestinal mucosal pathology after challenge with virulent C. perfringens. These results indicate that oral RASV expressing an alpha toxin C-terminal peptide induces protective immunity against NE.

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“…These recombinant Salmonella vaccines can target mucosal inductive tissues (PP) and ultimately disseminate and stimulate both mucosal and systemic arms of the immune system (29,30). It has been shown that the attenuated strain S. Typhi can serve as a safe and effective oral vaccine to prevent typhoid fever and serve as a live vector to deliver heterologous Ags in humans (31)(32)(33)(34). To enhance the immunogenicity of passenger Ag expression by live Salmonella vaccines (35), various types of promoters have been tested to enhance passenger Ag expression.…”

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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Recombinant Salmonella enterica serovar Typhi in a prime-boost strategy

Cited by 26 publications

References 45 publications

Use of mchI Encoding Immunity to the Antimicrobial Peptide Microcin H47 as a Plasmid Selection Marker in Attenuated Bacterial Live Vectors

Use of mchI Encoding Immunity to the Antimicrobial Peptide Microcin H47 as a Plasmid Selection Marker in Attenuated Bacterial Live Vectors

Recombinant AttenuatedSalmonella entericaSerovar Typhimurium Expressing the Carboxy-Terminal Domain of Alpha Toxin fromClostridium perfringensInduces Protective Responses against Necrotic Enteritis in Chickens

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

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