Discriminatory Analysis of Plague Antigens
Discriminatory Analysis of Plague Agent Antigens According to their Immunological Significance
Tech Area / Field
- BIO-CGM/Cytology, Genetics and Molecular Biology/Biotechnology
- BIO-SFS/Biosafety and BioSecurity/Biotechnology
3 Approved without Funding
Research Center of Toxicology and Hygienic Regulation of Biopreparations, Russia, Moscow reg., Serpukhov
- Kazakh Scientific Center for Quarantine and Zoonotic Diseases, Kazakstan, Almaty
- Ludwig-Maximilians-Universität / Max von Pettenkofer-Institut für Hygiene und Medizinische Mikrobiologie, Germany, Munich\nMichigan State University, USA, MI, East Lansing\nUniversity of Texas / Medical Branch, USA, TX, Galveston\nInstitut Pasteur, France, Paris\nUniversity of Kentucky, USA, KY, Lexington
Project summaryThe aim of the Project. To perform a selection of Yersinia pestis antigens promising for the construction of new effective molecular vaccines, to obtain their immunogenic forms and antibodies against them. To test the new anti-plague molecular vaccine under development by the Project participants based on LcrV, Pla and Psn antigens. To study a possibility of the vaccine perfection via an addition of other antigens as additional components.
Plague belongs to especially dangerous natural foci zoonosal transmissive diseases, the hosts of its infecting agent are wild rodents, and flea being its vectors. Natural plague foci occupy more than 7% of the global dry land. The existence of such a great number of plague active natural foci indicates the necessity of a permanent control over this especially dangerous disease. At present, bioterrorism as a proven fact adds another dimension to the importance of the construction of an effective and safe anti-plague vaccine. The construction of such a vaccine is directly connected with the achievements in the field of molecular biology and immunology of plague and demands join efforts of the scientists of many countries.
Now world practice includes two anti-plague vaccines: a live vaccine based on Y. pestis EV strain and a killed USP vaccine based on inactivated with formaldehyde and conserved with phenol cells of a virulent Y. Pestis strain.
In a number of countries, the live vaccine is not used for reasons of safety, as a reverse to virulence could not be excluded, especially at immunodeficiencies or unfavorable ecology. Inoculations with the live vaccine reduce both morbidity (on the average 10-fold) and mortality. However, live EV vaccine being active enough at the initial vaccination, is unfit for repeated re-vaccinations, as on the background of the initially formed immunity, the secondary taking of the live vaccine culture does not occur; besides, the available immunity level is not enough for the protection against virulent plague cells.
Inoculations with killed vaccine (multiple) reduce plague mortality, but do not down-regulate the morbidity. USP vaccine possesses a rather moderate protectivity for laboratory animals infected aerogenically with capsular FI+ cells of the plague agent and is practically unprotective regarding capsule-free FI variants of Y. pestis.
In the last two decades, the works on construction of anti-plague vaccines of a new generation lacking the drawbacks of the existing preparations became active. The main efforts in Russia were directed to a construction of a chemical anti-plague vaccine based on FI (Caf1) capsular antigen, obtained from the cells of the EV and ÎÑÀ vaccine strains, the antigen being a finally uncharacterized thermolabile polysaccharide-polypeptide complex.
In Great Britain and in the USA, the studies on the vaccine construction based on recombinant proteins of FI and V (LcrV) antigens of Y. pestis, including the ones based on a fusion protein from two molecules of the mentioned antigens gained the priority in the development of molecular anti-plague vaccines. These vaccine developments are on the clinical phase of their trails. Beside the above pathogenicity factors FI and V (LcrV), already used in molecular vaccines, a great attention is now paid to the study of antigens, such as Pla, Psn, Yops, LPS, and others. Selection of additional antigens to be included in the composition of the molecular anti-plague vaccine would be determined in the first place by their immunological significance in the formation of protective immunity.
The proposed Project includes the extended studies on evaluation of protective properties of Pla, Psn, YopD, LPS antigens in their various combinations as well as in combinations with well-known protective antigens FI, LcrV. Besides, monoclonal antibodies are planned to be obtained against the antigens under the Project in order to study them for their preventive properties. The obtained data on immunological significance of these antigens will enter a theoretical base for their inclusion into the composition of the vaccines of a new generation.
All the studies with virulent plague strains will be performed on the base of M.A. Aikimbaev’s Kazakh Scientific Center of Quarantine and Zoonosal Infections (KSCQZI) (Kazakhstan Republic).
Elaboration of protective antigens from recombinant E.coli strain-producers will be performed on the base of SFES RCT&HRB at FMBA of RF, Russia –and their immunogenic forms will be obtained for the testing on the base of KSCQZI, Kazakhstan.
The results of the study will be of a nation-wide importance to provide a Global Biodefence. Possible pathways of evolution of the endemic Central Asian Y.pestis strains will be determined thus providing a prognosis for further improvement of the means for specific defence.
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