Platform technology to deliver prophylactic molecules orally: An example using the Class A select agent Yersinia pestis

Río, Beatriz del; Fuente, Jesus Lajara; Neves, Vera; Dattwyler, Raymond J.; Seegers, Jos F. M. L.; Gomes-Solecki, Maria

doi:10.1016/j.vaccine.2010.07.084

Cited by 16 publications

(22 citation statements)

References 52 publications

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“…Analysis of localization and lipidation of the five vaccine constructs used in this study revealed that the OspA signal peptide tagged OspC K, OspB, BBK32, Salp15 and Salp25 for translocation across the cytoplasmic membrane, given that these proteins were primarily found in the envelope fraction (>60%) as opposed to the cytosolic fraction of the cell. Furthermore, OspC K, BBK32 and Salp15 constructs partitioned mostly into the detergent phase (Figure 3-1), the hydrophobic fraction of the E. coli cell envelope, consistent with protein lipidation and with our previous findings [110,114,115].…”

Section: Chapter 4 Discussion and Concluding Remarks Discussionsupporting

confidence: 89%

“…Our vaccine technology consisted of recombinant live E. coli expressing the leader sequence of B. burgdorferi OspA lipoprotein fused to the N-terminus of each candidate immunogen (OspC K, OspB, BBK32, Salp15 or Salp25), aiming to target them across the cytoplasmic membrane to the cell envelope as previously shown [110,114,115]. Analysis of localization and lipidation of the five vaccine constructs used in this study revealed that the OspA signal peptide tagged OspC K, OspB, BBK32, Salp15 and Salp25 for translocation across the cytoplasmic membrane, given that these proteins were primarily found in the envelope fraction (>60%) as opposed to the cytosolic fraction of the cell.…”

Section: Chapter 4 Discussion and Concluding Remarks Discussionmentioning

confidence: 99%

“…In contrast, mutation of the lipidation site generated a nonlipidated version of OspA that was localized mostly in the cell membrane [114]. We next applied this platform technology and developed Lactobacillus-based oral vaccines for plague [115] and E. colibased oral vaccines for Leptospirosis [110] where we were able to target the immunogens for translocation across the bacterial cytoplasmic membrane to the cell envelope as a consequence of lipid modification of the leader peptide OspA. The same rationale was applied to this work.…”

Section: Scope and Objectives Of Dissertationmentioning

confidence: 99%

“…By doing so, we generated the oral vaccine constructs, described in Table 2-1, expressing recombinant immunogens anchored to the cell envelope of the bacteria via a lipidated moiety [115]. Total extracts (TE) of our five oral vaccine constructs (E. coli expressing OspC K, OspB, BBK32, Salp15 and Salp25) along with the respective purified proteins (rOspC K, rOspB, rBBK32, rSalp15 and rSalp25) used as positive controls, were analyzed by denaturing polyacrylamide gels and protein expression was confirmed by Western blot.…”

Section: Construction Of Recombinant E Coli Expressing Ospc K Ospbmentioning

confidence: 99%

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Development of Oral Vaccines Against Lyme Disease

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Section: Chapter 4 Discussion and Concluding Remarks Discussionsupporting

confidence: 89%

Section: Chapter 4 Discussion and Concluding Remarks Discussionmentioning

confidence: 99%

Section: Scope and Objectives Of Dissertationmentioning

confidence: 99%

Section: Construction Of Recombinant E Coli Expressing Ospc K Ospbmentioning

confidence: 99%

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Development of Oral Vaccines Against Lyme Disease

Melo¹

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“…More recently, live bacterial vaccine vectors expressing Y. pestis virulence factors have been investigated for use as mucosal vaccines, which do not require injection and should produce higher levels of protection at mucosal surfaces than parenteral injection. Examples include the lactic acid commensal bacteria, Lactobacillus plantarum and an attenuated form of Salmonella enterica [18–20]. However, these live vector vaccines have yet to be fully evaluated.…”

Section: Introductionmentioning

confidence: 99%

Intranasal delivery of a protein subunit vaccine using a Tobacco Mosaic Virus platform protects against pneumonic plague

Arnaboldi

Sambir

D’Arco

et al. 2016

Vaccine

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Yersinia pestis, one of history’s deadliest pathogens, has killed millions over the course of human history. It has attributes that make it an ideal choice to produce mass casualties and is a prime candidate for use as a biological weapon. When aerosolized, Y. pestis causes pneumonic plague, a pneumonia that is 100% lethal if not promptly treated with effective antibiotics. Currently, there is no FDA approved plague vaccine. The current lead vaccine candidate, a parenterally administered protein subunit vaccine comprised of the Y. pestis virulence factors, F1 and LcrV, demonstrated variable levels of protection in primate pneumonic plague model. As the most likely mode of exposure in biological attack with Y. pestis is by aerosol, this raises a question of whether this parenteral vaccine will adequately protect humans against pneumonic plague. In the present study we evaluated two distinct mucosal delivery platforms for the intranasal (IN) administration of LcrV and F1 vaccine proteins, a live bacterial vector, Lactobacillus plantarum, and a tobacco mosaic virus (TMV) based delivery platform. IN administration of L. plantarum expressing LcrV, or TMV-conjugated to LcrV and F1 (TMV-LcrV+TMV-F1) resulted in the similar induction of high titers of IgG antibodies and evidence of proinflammatory cytokine secretion. However, only the TMV-conjugate delivery platform protected against subsequent lethal challenge with Y. pestis. TMV-LcrV+TMV-F1 co-vaccinated mice had no discernable morbidity and no mortality, while mice vaccinated with L. plantarum expressing LcrV or rLcrV+rF1 without TMV succumbed to infection or were only partially protected. Thus, TMV is a suitable mucosal delivery platform for an F1-LcrV subunit vaccine that induces complete protection against pneumonic infection with a lethal dose of Y. pestis in mice.

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Recombinant E. coli Dualistic Role as an Antigen-adjuvant Delivery Vehicle for Oral Immunization

Gomes-Solecki

Richer

2017

Methods in Molecular Biology

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Escherichia coli is the mainstay tool for fundamental microbiology research due to its ease of cultivation and safety. Auxotrophic strains of the K-12 and B lineages of E. coli are the organisms of choice to produce recombinant proteins. Components present in the cell envelope of bacteria are also potent immune modulators and have been used to develop adjuvants. We used live E. coli, after induction of recombinant protein expression, to develop a vehicle which has a dualistic function of producing vaccine while presenting itself as the adjuvant to deliver oral vaccines against a number of infectious diseases, including Lyme disease. Here, we give an example using E. coli expressing B. burgdorferi Outer Surface Protein A, which was proven effective in reducing B. burgdorferi burden in infected ticks after a 5-year field trial of a baited formulation containing this reservoir targeted vaccine.

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Platform technology to deliver prophylactic molecules orally: An example using the Class A select agent Yersinia pestis

Cited by 16 publications

References 52 publications

Development of Oral Vaccines Against Lyme Disease

Development of Oral Vaccines Against Lyme Disease

Intranasal delivery of a protein subunit vaccine using a Tobacco Mosaic Virus platform protects against pneumonic plague

Recombinant E. coli Dualistic Role as an Antigen-adjuvant Delivery Vehicle for Oral Immunization

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