Protective Activity and Safety of Acellular Pertussis Vaccine from Vaccine and Freshly Isolated Strain Bordetella pertussis

Goal. Study of the protective activity and safety of acellular pertussis vaccine (APV) using freshly isolated strain of B. pertussis. Materials and methods. Mice-hybrids F1 (CBAxC57Bl6). The B. pertussis strains: vaccine strains No. 305, No. 203, freshly isolated strain No. 287, the test neurotropic strain culture of B. pertussis No. 18323. Protective properties of the APV evaluated in accordance with the guidelines. Toxicity APV was studied by changes of body weight of mice, histamine-sensitizing properties, according to the instructions. The results and discussion. The paper presents the study of the safety and protective activity of three options acellular pertussis vaccine (APV) containing a complex of protective antigens of pertussis microbe: APV1 of vaccine strains of B. pertussis No. 305, serovariant 1.2.0, the gene for the pertussis toxin ptxA2, pertactin prnl gene, genes fimbria 2 and 3 - fim2-1 and fim3A and strain No. 203, serovariant 1.2.3, the gene for the pertussis toxin ptxA4, pertactin prnl gene, genes fimbria - fim2-1 and fim3A; APV2 of freshly isolated strain of B. pertussis No. 287, serovariant 1.0.3, the gene for the pertussis toxin ptxAl, gene pertactin prn2 genes fimbria -fim2-1 and fim3В; APV3 of strains No. 305, No. 203 and No. 287. Shows the relationship between the protective activity of the APV and genetic types, pertussis toxin, pertactin and fimrie in their composition. Protective activity APV1, APV2 and APV3 when infecting dose of 345 LD50 was 9.0 IPU/ml (international protective units per ml) of 10.3 IPU/ml and 19.9 IPU/ml, respectively. At extremely high dose of infection (3846 LD50) protective properties possessed only APV3, protective activity it was 9.2IPU/ml, in line with who requirements - at least 8 IPU/ml. Conclusion. Enhancing the protective effects of the vaccine APV3 and freshly isolated strain can be explained by the stimulation of cellular and humoral immunity to a broader spectrum of antigenic alternative structures in pertussis toxin, pertactin and fimrie.

штаммы B. pertussis, коклюшный токсин, пертактин, фимбрии, бесклеточная коклюшная вакцина, протектив-ная активность, strains of B. pertussis, pertussis toxin, pertactin, fimbriae, acellular pertussis vaccine, protective activity

1. Shinkarev A.S., Mertsalova N.U., Mazurova I. K. , Borisova O.Y., Zakharova N.S. Ozeretskovskaya M.N. et al. Modern strains of B. рertussis: immunobiological properties and improvement of vaccines. Zhurnal mikrobiologii, epidemiologii i immunobiologii. [Journal of Microbiology, Epidemiology and Immunobiology]. 2007; 4: 20 – 25 (in Russian)

2. Bouchez V., Hegerle N., Strati F., Njamkepo E., Guiso N. New Data on Vaccine Antigen Deficient Bordetella pertussis Isolates. Vaccines (Basel). 2015; Sept 14; 3 (3): 751 – 770.

3. Sealey K.L., Harris S.R., Fry N.K., Hurst L.D., Gorringe A.R., Parkhill J. et al. Genomic analysis of isolates from the United Kingdom 2012 pertussisoutbreak reveals thet vaccine antigen genes are unusually fast evolving. J. Infect. Dis. 2015 Jul 15; 212 (2): 294 – 301.

4. Rumbo M., Hozdor D. Development of improved pertussis vaccine. Hum Vaccin. Immunother. 2014; 10 (8): 2450 – 2453.

5. Bowden K.E., Weigand M.R., Peng Y., Cassiday P.K., Sammons S., Knipe K., et al. Genome structural diversity among 31 Bordetella pertussis isolates from two recent U.S. whooping cough statewide epidemics. mSphere. 2016; May 11;1(3) pii:e00036-16.

6. Mooi F.R. Bordetella pertussis and vaccination: the persistence of a genetically monomorphic pathogen. Infect. Genet. Evol. 2010; 10 (1): 36 – 49.

7. Borisova O. Yu., Petrova M. S., Mazurova I. K., Lytkina I. N., Popova O. K., Gadua N. T. et al. Features of pertussis infection in various periods of the epidemic process in Moscow. Zhurnal mikrobiologii, epidemiologii i immunobiologii.. [Journal Microbiology, Еpidemiology and Immunobiology]. 2010; 4: 33 – 39 (in Russian).

8. Mertsalova N.U., Borisova O. Yu., Shinkarev A. S., Britsina M. V., Ozeretskovskaya M. N., Mazurova I. K., et al. The Dynamics of changes in patho-genetic properties of strains of B. pertussis. Zhurnal mikrobiologii, epidemiologii i immunobiologii. [Journal of Microbiology, Epidemiology and Immunobiology]. 2009; 6: 7 – 11 (in Russian).

9. Karataev G. I., Sinyashin L. N., Medkova, A. Yu., Semin E. P. Percy-stancia bacteria Bordetella pertussis and possible mechanism of its formation. Journal of Microbiology, epidemiology and immunobiology. 2015; 6: 114 – 121 (in Russian).

10. Lowry O.H., Rosebrough N.J., Farr A.L., Randall R.J. Protein measurement with the Folin rea-gent. J. Biol. Chem. 1951; 193: 265 – 275.

11. The who expert Committee on biological standardization. Technical report series 800. The world Health organization, Geneva.1992: 80 – 170. (in Russian)

12. The guidelines for preclinical studies of pharmaceuticals (immunobiological preparations) part 2, Moscow/ 2012 (in Russian)/

13. Zakharova N.S. Britsina M.V., Mertsalova N.U., Bazhanova, I. G., Ozeretskovskaya M. N., Zaitsev, E. M. et al. Domestic acellular pertussis vaccine. Zhurnal mikrobiologii, epidemiologii i immunobiologii. [ Journal of Microbiology, Еpidemiology and Imunobiology]. 2008; 1: 35 – 41 (in Russian).