LcrV Delivered via Type III Secretion System of Live Attenuated Yersinia pseudotuberculosis Enhances Immunogenicity against Pneumonic Plague

Sun, Wei; Sanapala, Shilpa; Henderson, Jeremy C.; Sam, Shandiin; Olinzock, Joseph; Trent, M. Stephen; Curtiss, Roy

doi:10.1128/iai.02173-14

Cited by 19 publications

(21 citation statements)

References 101 publications

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“…challenge with ~130 LD 50 (1.3 × 10 4 CFU) of Y. pestis KIM6+ (pCD1Ap) than induced by χ10057(pYA3332) (40% survival). Splenocytes from mice vaccinated with χ10057(pYA5199) produced significant levels of IFN-γ, TNF-α, and IL-17 after restimulation with LcrV and YpL antigens [149]. …”

Section: Live Attenuated Yersinia Vaccinesmentioning

confidence: 99%

Plague Vaccines: Status and Future

Sun

2016

Advances in Experimental Medicine and Biology

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Three major plague pandemics caused by the gram-negative bacterium Yersinia pestis have killed nearly 200 million people in human history. Due to its extreme virulence and the ease of its transmission, Y. pestis has been used purposefully for biowarfare in the past. Currently, plague epidemics are still breaking out sporadically in most of parts of the world, including the United States. Approximately 2000 cases of plague are reported each year to the World Health Organization. However, the potential use of the bacteria in modern times as an agent of bioterrorism and the emergence of a Y. pestis strain resistant to eight antibiotics bring out severe public health concerns. Therefore, prophylactic vaccination against this disease holds the brightest prospect for its long-term prevention. Here, we summarize the progress of the current vaccine development for counteracting plague.

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Section: Live Attenuated Yersinia Vaccinesmentioning

confidence: 99%

Plague Vaccines: Status and Future

Sun

2016

Advances in Experimental Medicine and Biology

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“…Compared to the wild-type Yptb PB1+ (LD 50 , 1.5×10 8 CFU) [32], 9 of 13 Swiss Webster mice survived oral administration of 1.2×10 9 CFU χ10061, which indicated that the caf1 operon chromosome insertion resulted in around 10-fold attenuation ( its LD 50 , more than 1.2× 10 9 CFU ). χ10062 with additional Δ yopK mutation, and χ10068 with additional Δ yopK Δ yopJ mutations were much attenuated.…”

Section: Resultsmentioning

confidence: 99%

“…Mice were acclimated for one week after arrival and deprived of food and water for 6 h before starting experiments. The procedures for animal inoculation and colonization were described in our previous report [32]. Briefly, Bacteria were harvested by centrifugation at 24°C and resuspended in 0.5 ml buffered saline with gelatin (BSG).…”

Section: Methodsmentioning

confidence: 99%

Oral administration of a recombinant attenuated Yersinia pseudotuberculosis strain elicits protective immunity against plague

Sun

Sanapala

Rahav

et al. 2015

Vaccine

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A Yersinia pseudotuberculosis PB1+ (Yptb PB1+) mutant strain combined with chromosome insertion of the caf1R-caf1A-caf1M-caf1 operon and deletions of yopJ and yopK, χ10068 [pYV-ω2 (ΔyopJ315 ΔyopK108) ΔlacZ044::caf1R-caf1M-caf1A-caf1] was constructed. Results indicated that gene insertion and deletion did not affect the growth rate of χ10068 compared to wild-type Yptb cultured at 26°C. In addition, the F1 antigen in χ10068 was synthesized and secreted on the surface of bacteria at 37°C (mammalian body temperature), not at ambient culture temperature (26°C). Immunization with χ10068 primed antibody responses and specific T-cell responses to F1 and YpL (Y. pestis whole cell lysate). Oral immunization with a single dose of χ10068 provided 70% protection against a subcutaneous (s.c.) challenge with ~2.6 × 105 LD50 of Y. pestis KIM6+ (pCD1Ap) (KIM6+Ap) and 90% protection against an intranasal (i.n.) challenge with ~500 LD50 of KIM6+Ap in mice. Our results suggest that χ10068 can be used as an effective precursor to make a safe vaccine to prevent plague in humans and to eliminate plague circulation among humans and animals.

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“…Typhimurium mutant strains were constructed using conjugation with suicide vectors [13]. Parental S .…”

Section: Methodsmentioning

confidence: 99%

“…challenge with Y. pestis CO92 [12]. Also, immunization with a RASV delivering YadC induced partial protection in mice against bubonic plague, but not pneumonic plague [13]. However, YadC synthesis is toxic to bacteria, and can seriously hinder bacterial growth.…”

Section: Introductionmentioning

confidence: 99%

Multiple antigens of Yersinia pestis delivered by live recombinant attenuated Salmonella vaccine strains elicit protective immunity against plague

Sanapala

Rahav

Patel

et al. 2016

Vaccine

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Based on our improved novel Salmonella vaccine delivery platform, we optimized the recombinant attenuated Salmonella Typhimurium vaccine (RASV) χ12094 to deliver multiple Y. pestis antigens. These included LcrV196 (amino acids, 131 to 326), Psn encoded on pYA5383 and F1 encoded in the chromosome, their synthesis did not cause adverse effects on bacterial growth. Oral immunization with χ12094(pYA5383) simultaneously stimulated high antibody titers to LcrV, Psn and F1 in mice and presented complete protection against both subcutaneous (s.c.) and intranasal (i.n.) challenges with high lethal doses of Y. pestis CO92. Moreover, no deaths or other disease symptoms were observed in SCID mice orally immunized with χ12094(pYA5383) over a 60 day period. Therefore, the trivalent S. Typhimurium-based live vaccine shows promise for a next-generation plague vaccine.

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LcrV Delivered via Type III Secretion System of Live Attenuated Yersinia pseudotuberculosis Enhances Immunogenicity against Pneumonic Plague

Cited by 19 publications

References 101 publications

Plague Vaccines: Status and Future

Plague Vaccines: Status and Future

Oral administration of a recombinant attenuated Yersinia pseudotuberculosis strain elicits protective immunity against plague

Multiple antigens of Yersinia pestis delivered by live recombinant attenuated Salmonella vaccine strains elicit protective immunity against plague

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