Yersinia pestis Live Vaccine with Improved Characteristics

V. A. Feodorova, L. N. Pan'kina, E. P. Savostina, O. S. Kuznetsov, N. P. Konnov, L. V. Sayapina, S. V. Dentovskaya, R. Z. Shaikhutdinova, S. A. Ageev, B. Lindner, A. N. Kondakova, N. A. Kocharova, S. N. Senchenkova, O. Holst, G. B. Pier, Y. A. Knirel, A. P. Anisimov, Vladimir Motin

Research output: Contribution to journalArticle

Abstract

The live plague vaccine strain Y. pestis EV line NIIEG widely used for human and animal immunisation proves a high level of specific immunity against both bubonic and pneumonic plague. We constructed an EV NIIEG mutant in the acyltransferase gene lpxM that resulted in the production of a less toxic penta-acylated lipid A of lipopolysaccharide (LPS) of Y. pestis, tested the synthesis and immunoreactivity of the major known antigens involved in virulence and eliciting immunity against plague, and also evaluated the protective properties of the lpxM derivative. The expression of antigens was determined by dot-ELISA, immunoblotting, the indirect hemagglutination test, electron microscopy (capsule), and fibrinolytic and plasma-coagulase activities (plasminogen activator Pla). Stumulation of TNF-alpha production with different types of LPS was revealed by using the J774 macrophage-like cell line. The antibody immune response, followed by immunisation, was estimated by ELISA. Protective efficacy was evaluated in mice and guinea pigs by subcutaneous challenge with the wild-type Y. pestis 231. In comparison with the parental strain, the lpxM mutant was found to produce a reduced amount of capsular antigen F1, multifunctional virulence factor LcrV and murine toxin Ymt as well as had an altered activity of Pla. Moreover, this mutant possessed a modified cell surface as jusjed by the immunoreactivity with monoclonal antibodies to different carbohydrate epitopes and by the resistant phenotype to the plague diagnostic bacteriophage L-413C. The penta-acylated LPS of Y. pestis revealed a reduced capacity of stimulating TNF-alpha in vitro. Immunisation with the lpxM mutant provided an enhanced protection over the original Y. pestis EV NIIEG in both mice and guinea pigs. Thus, the pleiotropic effect of the lpxM mutation led to the construction of the live plague candidate vaccine strain with improved characteristics toward safety, reactogenicity and protective properties.

Original languageEnglish (US)
Pages (from-to)97-100
Number of pages4
JournalProcedia in Vaccinology
Volume1
Issue number1
DOIs
StatePublished - 2009

Fingerprint

Yersinia pestis
Plague
Vaccines
Plague Vaccine
Lipopolysaccharides
Immunization
Rubiaceae
Antigens
Immunity
Guinea Pigs
Tumor Necrosis Factor-alpha
Enzyme-Linked Immunosorbent Assay
Acyltransferases
Hemagglutination Tests
Lipid A
Plasminogen Activators
Poisons
Coagulase
Virulence Factors
Immunoblotting

Keywords

  • Live plague vaccine
  • lpxM (msbB) mutant
  • Plague immunity
  • Pleiotropic effect
  • Yersinia pestis EV NIIEG

ASJC Scopus subject areas

  • Immunology
  • Infectious Diseases
  • Drug Discovery
  • Pharmaceutical Science

Cite this

Feodorova, V. A., Pan'kina, L. N., Savostina, E. P., Kuznetsov, O. S., Konnov, N. P., Sayapina, L. V., ... Motin, V. (2009). Yersinia pestis Live Vaccine with Improved Characteristics. Procedia in Vaccinology, 1(1), 97-100. https://doi.org/10.1016/j.provac.2009.07.017

Yersinia pestis Live Vaccine with Improved Characteristics. / Feodorova, V. A.; Pan'kina, L. N.; Savostina, E. P.; Kuznetsov, O. S.; Konnov, N. P.; Sayapina, L. V.; Dentovskaya, S. V.; Shaikhutdinova, R. Z.; Ageev, S. A.; Lindner, B.; Kondakova, A. N.; Kocharova, N. A.; Senchenkova, S. N.; Holst, O.; Pier, G. B.; Knirel, Y. A.; Anisimov, A. P.; Motin, Vladimir.

In: Procedia in Vaccinology, Vol. 1, No. 1, 2009, p. 97-100.

Research output: Contribution to journalArticle

Feodorova, VA, Pan'kina, LN, Savostina, EP, Kuznetsov, OS, Konnov, NP, Sayapina, LV, Dentovskaya, SV, Shaikhutdinova, RZ, Ageev, SA, Lindner, B, Kondakova, AN, Kocharova, NA, Senchenkova, SN, Holst, O, Pier, GB, Knirel, YA, Anisimov, AP & Motin, V 2009, 'Yersinia pestis Live Vaccine with Improved Characteristics', Procedia in Vaccinology, vol. 1, no. 1, pp. 97-100. https://doi.org/10.1016/j.provac.2009.07.017
Feodorova VA, Pan'kina LN, Savostina EP, Kuznetsov OS, Konnov NP, Sayapina LV et al. Yersinia pestis Live Vaccine with Improved Characteristics. Procedia in Vaccinology. 2009;1(1):97-100. https://doi.org/10.1016/j.provac.2009.07.017
Feodorova, V. A. ; Pan'kina, L. N. ; Savostina, E. P. ; Kuznetsov, O. S. ; Konnov, N. P. ; Sayapina, L. V. ; Dentovskaya, S. V. ; Shaikhutdinova, R. Z. ; Ageev, S. A. ; Lindner, B. ; Kondakova, A. N. ; Kocharova, N. A. ; Senchenkova, S. N. ; Holst, O. ; Pier, G. B. ; Knirel, Y. A. ; Anisimov, A. P. ; Motin, Vladimir. / Yersinia pestis Live Vaccine with Improved Characteristics. In: Procedia in Vaccinology. 2009 ; Vol. 1, No. 1. pp. 97-100.
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AU - Sayapina, L. V.

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AU - Shaikhutdinova, R. Z.

AU - Ageev, S. A.

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AU - Kondakova, A. N.

AU - Kocharova, N. A.

AU - Senchenkova, S. N.

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