Protection and Safety Evaluation of Live Constructions Derived from the Pgm− and pPCP1− Yersinia pestis Strain
Abstract
:1. Introduction
2. Materials and Methods
2.1. Bacterial Strains, Plasmids, and Culture Conditions
2.2. Mice
2.3. Construction of Y. pestis Mutant Strains
2.4. Virulence Analysis in Mice
2.5. Determination of Protective Efficacy
2.6. Immune Responses
2.7. Evaluation of Vaccine Safety
2.8. Statistical Analysis
3. Results
3.1. Construction of Y. pestis Mutants with Lipid A Modification
3.2. Virulence of Y. pestis Mutants in Mice and Protective Immunity
3.3. Protection Efficiency Against Pulmonary Y. pestis Infection and Serum Immune Responses
3.4. Safety Assessment of Y. pestis Mutant Strains
4. Discussion
5. Conclusions
Author Contributions
Funding
Acknowledgments
Financial Disclosure
Conflicts of Interest
References
- Girard, G. Immunity in plague. Acquisitions supplied by 30 years of work ont the “Pasteurella pestis EV” (Girard and Robic) strain. Biol. Med. (Paris) 1963, 52, 631–731. [Google Scholar] [PubMed]
- Titball, R.W.; Williamson, E.D. Yersinia pestis (plague) vaccines. Expert Opin. Biol. Ther. 2004, 4, 965–973. [Google Scholar] [CrossRef] [PubMed]
- Feodorova, V.A.; Corbel, M.J. Prospects for new plague vaccines. Expert Rev. Vaccines 2009, 8, 1721–1738. [Google Scholar] [CrossRef] [PubMed]
- Hallett, A.F.; Isaacson, M.; Meyer, K.F. Pathogenicity and immunogenic efficacy of a live attentuated plaque vaccine in vervet monkeys. Infect. Immun. 1973, 8, 876–881. [Google Scholar] [CrossRef] [Green Version]
- Meyer, K.F.; Cavanaugh, D.C.; Bartelloni, P.J.; Marshall, J.D., Jr. Plague immunization. I. Past and present trends. J. Infect. Dis. 1974, 129 (Suppl. 1), S13–S18. [Google Scholar] [CrossRef]
- Meyer, K.F.; Smith, G.; Foster, L.; Brookman, M.; Sung, M. Live, attenuated Yersinia pestis vaccine: Virulent in nonhuman primates, harmless to guinea pigs. J. Infect. Dis. 1974, 129 (Suppl. 1), S85–S120. [Google Scholar] [CrossRef]
- Russell, P.; Eley, S.M.; Hibbs, S.E.; Manchee, R.J.; Stagg, A.J.; Titball, R.W. A comparison of Plague vaccine, USP and EV76 vaccine induced protection against Yersinia pestis in a murine model. Vaccine 1995, 13, 1551–1556. [Google Scholar] [CrossRef]
- Une, T.; Brubaker, R.R. In vivo comparison of avirulent Vwa- and Pgm- or Pstr phenotypes of yersiniae. Infect. Immun. 1984, 43, 895–900. [Google Scholar] [CrossRef] [Green Version]
- CDC. Update: Human plague India 1994. CDC Morb. Mortal. Wkly. Rep. 1995, 43, 722–723. [Google Scholar]
- Batra HV, T.U. Agarwal GS Isolation and identification of Yersinia pestis responsible for the recent plague outbreaks in India. Curr. Sci. 1996, 71, 787–791. [Google Scholar]
- Frank, K.M.; Schneewind, O.; Shieh, W.J. Investigation of a Researcher’s Death Due to Septicemic Plague. N. Engl. J. Med. 2011, 364, 2563–2564. [Google Scholar] [CrossRef] [PubMed]
- Quenee, L.E.; Hermanas, T.M.; Ciletti, N.; Louvel, H.; Miller, N.C.; Elli, D.; Blaylock, B.; Mitchell, A.; Schroeder, J.; Krausz, T.; et al. Hereditary hemochromatosis restores the virulence of plague vaccine strains. J. Infect. Dis. 2012, 206, 1050–1058. [Google Scholar] [CrossRef] [PubMed]
- Meyer, K.F. Effectiveness of live or killed plague vaccines in man. Bull. World Health Organ. 1970, 42, 653–666. [Google Scholar] [PubMed]
- WHO Expert Committee on Plague. W.H.O. Technical Report Series 447:16; WHO: Geneva, Switzerland, 1970. [Google Scholar]
- Yazdanpanah, Y. Efficacy trials of Plague Vaccines: Endpoints, trial design, site selection. In Proceedings of the WHO Workshop 2018, Paris, France, 23 April 2018; INSERM: Paris, France, 2018. [Google Scholar]
- Telepnev, M.V.; Klimpel, G.R.; Haithcoat, J.; Knirel, Y.A.; Anisimov, A.P.; Motin, V.L. Tetraacylated lipopolysaccharide of Yersinia pestis can inhibit multiple Toll-like receptor-mediated signaling pathways in human dendritic cells. J. Infect. Dis. 2009, 200, 1694–1702. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Montminy, S.W.; Khan, N.; McGrath, S.; Walkowicz, M.J.; Sharp, F.; Conlon, J.E.; Fukase, K.; Kusumoto, S.; Sweet, C.; Miyake, K.; et al. Virulence factors of Yersinia pestis are overcome by a strong lipopolysaccharide response. Nat. Immunol. 2006, 7, 1066–1073. [Google Scholar] [CrossRef]
- Matsuura, M.; Takahashi, H.; Watanabe, H.; Saito, S.; Kawahara, K. Immunomodulatory effects of Yersinia pestis lipopolysaccharides on human macrophages. Clin. Vaccine Immunol. 2010, 17, 49–55. [Google Scholar] [CrossRef] [Green Version]
- Raetz, C.R.; Whitfield, C. Lipopolysaccharide endotoxins. Annu. Rev. Biochem. 2002, 71, 635–700. [Google Scholar] [CrossRef] [Green Version]
- Sun, W.; Six, D.; Kuang, X.Y.; Roland, K.L.; Raetz, C.R.H.; Curtiss, R. A live attenuated strain of Yersinia pestis KIM as a vaccine against plague. Vaccine 2011, 29, 2986–2998. [Google Scholar] [CrossRef] [Green Version]
- Sun, W.; Six, D.A.; Reynolds, C.M.; Chung, H.S.; Raetz, C.R.; Curtiss, R., 3rd. Pathogenicity of Yersinia pestis synthesis of 1-dephosphorylated lipid A. Infect. Immun. 2013, 81, 1172–1185. [Google Scholar] [CrossRef] [Green Version]
- Thoelen, S.; Van Damme, P.; Mathei, C.; Leroux-Roels, G.; Desombere, I.; Safary, A.; Vandepapeliere, P.; Slaoui, M.; Meheus, A. Safety and immunogenicity of a hepatitis B vaccine formulated with a novel adjuvant system. Vaccine 1998, 16, 708–714. [Google Scholar] [CrossRef]
- Takayama, K.; Ribi, E.; Cantrell, J.L. Isolation of a nontoxic lipid A fraction containing tumor regression activity. Cancer Res. 1981, 41, 2654–2657. [Google Scholar] [PubMed]
- Vuopiovarkila, J.; Nurminen, M.; Pyhala, L.; Makela, P.H. Lipopolysaccharide-Induced Non-Specific Resistance to Systemic Escherichia-Coli Infection in Mice. J. Med. Microbiol. 1988, 25, 197–203. [Google Scholar] [CrossRef] [PubMed]
- Lathem, W.W.; Price, P.A.; Miller, V.L.; Goldman, W.E. A plasminogen-activating protease specifically controls the development of primary pneumonic plague. Science 2007, 315, 509–513. [Google Scholar] [CrossRef]
- Welkos, S.L.; Friedlander, A.M.; Davis, K.J. Studies on the role of plasminogen activator in systemic infection by virulent Yersinia pestis strain CO92. Microb. Pathog. 1997, 23, 211–223. [Google Scholar] [CrossRef] [PubMed]
- Sodeinde, O.A.; Subrahmanyam, Y.V.; Stark, K.; Quan, T.; Bao, Y.; Goguen, J.D. A surface protease and the invasive character of plague. Science 1992, 258, 1004–1007. [Google Scholar] [CrossRef] [PubMed]
- Caulfield, A.J.; Walker, M.E.; Gielda, L.M.; Lathem, W.W. The Pla protease of Yersinia pestis degrades fas ligand to manipulate host cell death and inflammation. Cell Host Microbe 2014, 15, 424–434. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Smiley, S.T.; Szaba, F.M.; Kummer, L.W.; Duso, D.K.; Lin, J.S. Yersinia pestis Pla protein thwarts T cell defense against plague. Infect. Immun. 2019. [Google Scholar] [CrossRef] [Green Version]
- Sebbane, F.; Jarrett, C.O.; Gardner, D.; Long, D.; Hinnebusch, B.J. Role of the Yersinia pestis plasminogen activator in the incidence of distinct septicemic and bubonic forms of flea-borne plague. Proc. Natl. Acad. Sci. USA 2006, 103, 5526–5530. [Google Scholar] [CrossRef] [Green Version]
- Agar, S.L.; Sha, J.; Baze, W.B.; Erova, T.E.; Foltz, S.M.; Suarez, G.; Wang, S.; Chopra, A.K. Deletion of Braun lipoprotein gene (lpp) and curing of plasmid pPCP1 dramatically alter the virulence of Yersinia pestis CO92 in a mouse model of pneumonic plague. Microbiology 2009, 155, 3247–3259. [Google Scholar] [CrossRef] [Green Version]
- Straley, S.C.; Bowmer, W.S. Virulence genes regulated at the transcriptional level by Ca2+ in Yersinia pestis include structural genes for outer membrane proteins. Infect. Immun. 1986, 51, 445–454. [Google Scholar] [CrossRef] [Green Version]
- Pujol, C.; Grabenstein, J.P.; Perry, R.D.; Bliska, J.B. Replication of Yersinia pestis in interferon gamma-activated macrophages requires ripA, a gene encoded in the pigmentation locus. Proc. Natl. Acad. Sci. USA 2005, 102, 12909–12914. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Datsenko, K.A.; Wanner, B.L. One-step inactivation of chromosomal genes in Escherichia coli K-12 using PCR products. Proc. Natl. Acad. Sci. USA 2000, 97, 6640–6645. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Sun, W.; Wang, S.; Curtiss, R., 3rd. Highly efficient method for introducing successive multiple scarless gene deletions and markerless gene insertions into the Yersinia pestis chromosome. Appl. Environ. Microbiol. 2008, 74, 4241–4245. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ajioka, R.S.; Levy, J.E.; Andrews, N.C.; Kushner, J.P. Regulation of iron absorption in Hfe mutant mice. Blood 2002, 100, 1465–1469. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Sun, W.; Roland, K.L.; Branger, C.G.; Kuang, X.; Curtiss, R., 3rd. The role of relA and spoT in Yersinia pestis KIM5 pathogenicity. PLoS ONE 2009, 4, e6720. [Google Scholar] [CrossRef] [Green Version]
- Quenee, L.E.; Cornelius, C.A.; Ciletti, N.A.; Elli, D.; Schneewind, O. Yersinia pestis caf1 variants and the limits of plague vaccine protection. Infect. Immun. 2008, 76, 2025–2036. [Google Scholar] [CrossRef] [Green Version]
- Sukumaran, A.; Chang, J.; Han, M.; Mintri, S.; Khaw, B.A.; Kim, J. Iron overload exacerbates age-associated cardiac hypertrophy in a mouse model of hemochromatosis. Sci. Rep. 2017, 7, 5756. [Google Scholar] [CrossRef] [Green Version]
- Fellows, P.; Lin, W.; Detrisac, C.; Hu, S.C.; Rajendran, N.; Gingras, B.; Holland, L.; Price, J.; Bolanowski, M.; House, R.V. Establishment of a Swiss Webster mouse model of pneumonic plague to meet essential data elements under the animal rule. Clin. Vaccine Immunol. 2012, 19, 468–476. [Google Scholar] [CrossRef]
- Anderson, G.W., Jr.; Heath, D.G.; Bolt, C.R.; Welkos, S.L.; Friedlander, A.M. Short- and long-term efficacy of single-dose subunit vaccines against Yersinia pestis in mice. Am. J. Trop. Med. Hyg. 1998, 58, 793–799. [Google Scholar] [CrossRef] [Green Version]
- Heath, D.G.; Anderson, G.W., Jr.; Mauro, J.M.; Welkos, S.L.; Andrews, G.P.; Adamovicz, J.; Friedlander, A.M. Protection against experimental bubonic and pneumonic plague by a recombinant capsular F1-V antigen fusion protein vaccine. Vaccine 1998, 16, 1131–1137. [Google Scholar] [CrossRef]
- Hinnebusch, B.J.; Perry, R.D.; Schwan, T.G. Role of the Yersinia pestis hemin storage (hms) locus in the transmission of plague by fleas. Science 1996, 273, 367–370. [Google Scholar] [CrossRef] [PubMed]
- Bobrov, A.G.; Kirillina, O.; Forman, S.; Mack, D.; Perry, R.D. Insights into Yersinia pestis biofilm development: Topology and co-interaction of Hms inner membrane proteins involved in exopolysaccharide production. Environ. Microbiol. 2008, 10, 1419–1432. [Google Scholar] [CrossRef] [PubMed]
- Fetherston, J.D.; Kirillina, O.; Bobrov, A.G.; Paulley, J.T.; Perry, R.D. The yersiniabactin transport system is critical for the pathogenesis of bubonic and pneumonic plague. Infect. Immun. 2010, 78, 2045–2052. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Feodorova, V.A.; Pan’kina, L.N.; Savostina, E.P.; Sayapina, L.V.; Motin, V.L.; Dentovskaya, S.V.; Shaikhutdinova, R.Z.; Ivanov, S.A.; Lindner, B.; Kondakova, A.N.; et al. A Yersinia pestis lpxM-mutant live vaccine induces enhanced immunity against bubonic plague in mice and guinea pigs. Vaccine 2007, 25, 7620–7628. [Google Scholar] [CrossRef] [PubMed]
- Philipovskiy, A.V.; Smiley, S.T. Vaccination with live Yersinia pestis primes CD4 and CD8 T cells that synergistically protect against lethal pulmonary Y. pestis infection. Infect. Immun. 2007, 75, 878–885. [Google Scholar] [CrossRef] [Green Version]
- Szaba, F.M.; Kummer, L.W.; Wilhelm, L.B.; Lin, J.S.; Parent, M.A.; Montminy-Paquette, S.W.; Lien, E.; Johnson, L.L.; Smiley, S.T. D27-pLpxL, an avirulent strain of Yersinia pestis, primes T cells that protect against pneumonic plague. Infect. Immun. 2009, 77, 4295–4304. [Google Scholar] [CrossRef] [PubMed] [Green Version]
Strain | Relevant Genotype or Annotation | Source |
---|---|---|
E. coli TOP10 | F− mcrA ∆(mrr-hsdRMS-mcrBC) φ80lacZ∆M15 ∆lacX74 recA1 araD139 ∆(ara-leu)7697 galU galK rpsL endA1 nupG | Invitrogen |
Y. pestis KIM6+(pCD1Ap) | Pgm+, pMT1, pPCP1, pCD1Ap | (1) |
Y. pestis KIM10 | Pgm−, pMT1, pPCP1− | [33] |
YPS19 | ∆lpxP32::PlpxL lpxL Pgm− pPCP1− | This study |
YPS20 | ∆lpxP32::PlpxL lpxL ∆lacI23::Plpp lpxE Pgm− pPCP1− | This study |
KIM10(pCD1Ap) | pCD1Ap, pPCP1−, Pgm− | This study |
YPS19(pCD1Ap) | pCD1Ap, pPCP1−, Pgm−, ∆lpxP32::PlpxL lpxL | This study |
YPS20(pCD1Ap) | pCD1Ap, pPCP1−, Pgm−, ∆lpxP32::PlpxL lpxL ∆lacI23::Plpp lpxE | This study |
Plasmid | Source | |
pKD46 | λ Red recombinase expression plasmid | [34] |
pYA4373 | The cat-sacB cassette in the PstI and SacI sites of pUC18. | [35] |
pYA4577 | The PlpxLlpxL gene fragment flanked by the lpxP upstream and downstream sequence | [20] |
pYA4578 | The cat-sacB-PlpxLlpxL gene fragment flanked by the lpxP upstream and downstream sequence | [20] |
pYA4735 | The Plpp lpxE gene fragment flanked by the lacI upstream and downstream sequence | [21] |
pYA4736 | The cat-sacB-Plpp lpxE gene fragment flanked by the lacI upstream and downstream sequence | [21] |
Name | Sequence |
---|---|
LpxL1 | 5′gggagctccgctgatttgcgcgttaatgccctca3′ |
LpxL2 | 5′cggctgcaggaacataagaagaaaagataag3′ |
LpxE1 | 5′cgggagctcggataaccagaagcaataaaaaatc3′ |
LpxE2 | 5′cgggagctcctaaataatctcacgattacgca3′ |
Cm-V | 5′gttgtccatattggccacgttta3′ |
SacB-V | 5′gcagaagagatatttttaattgtgga3′ |
pPCP1−V1 | 5′cgggaattcagcaaaacagacaaacgcctgctgg3′ |
pPCP1−V2 | 5′cggctgcagtagacacccttaatctctctgcatg3′ |
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Wang, X.; Singh, A.K.; Sun, W. Protection and Safety Evaluation of Live Constructions Derived from the Pgm− and pPCP1− Yersinia pestis Strain. Vaccines 2020, 8, 95. https://doi.org/10.3390/vaccines8010095
Wang X, Singh AK, Sun W. Protection and Safety Evaluation of Live Constructions Derived from the Pgm− and pPCP1− Yersinia pestis Strain. Vaccines. 2020; 8(1):95. https://doi.org/10.3390/vaccines8010095
Chicago/Turabian StyleWang, Xiuran, Amit K. Singh, and Wei Sun. 2020. "Protection and Safety Evaluation of Live Constructions Derived from the Pgm− and pPCP1− Yersinia pestis Strain" Vaccines 8, no. 1: 95. https://doi.org/10.3390/vaccines8010095
APA StyleWang, X., Singh, A. K., & Sun, W. (2020). Protection and Safety Evaluation of Live Constructions Derived from the Pgm− and pPCP1− Yersinia pestis Strain. Vaccines, 8(1), 95. https://doi.org/10.3390/vaccines8010095