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Preclinical studies of safety, immunogenicity and protective activity of attenuated Bordetella pertussis bacteria on the Macaca mulatta model

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1. Title Title of document Preclinical studies of safety, immunogenicity and protective activity of attenuated Bordetella pertussis bacteria on the Macaca mulatta model
2. Creator Author's name, affiliation, country Alisa Yu. Medkova; Federal Research Centre for Epidemiology and Microbiology named after the honorary academician N.F. Gamaleya;
Central Сlinical Hospital with a Polyclinic, Office of the President of the Russian Federation; Россия
2. Creator Author's name, affiliation, country Lyudmila N. Sinyashina; Federal Research Centre for Epidemiology and Microbiology named after the honorary academician N.F. Gamaleya; Россия
2. Creator Author's name, affiliation, country Astanda A. Amichba; Research Institute of Experimental Pathology and Therapy of the Academy of Sciences of Abkhazia;
2. Creator Author's name, affiliation, country Evgeniy G. Semin; Federal Research Centre for Epidemiology and Microbiology named after the honorary academician N.F. Gamaleya; Россия
2. Creator Author's name, affiliation, country Zinaida V. Shevtsova; Research Institute of Experimental Pathology and Therapy of the Academy of Sciences of Abkhazia;
Abkhazian State University;
2. Creator Author's name, affiliation, country Alisa Z. Matua; Research Institute of Experimental Pathology and Therapy of the Academy of Sciences of Abkhazia;
Abkhazian State University;
2. Creator Author's name, affiliation, country Anush A. Djidaryan; Research Institute of Experimental Pathology and Therapy of the Academy of Sciences of Abkhazia;
2. Creator Author's name, affiliation, country Dzhenni T. Kubrava; Research Institute of Experimental Pathology and Therapy of the Academy of Sciences of Abkhazia;
2. Creator Author's name, affiliation, country Irina G. Kondzhariya; Research Institute of Experimental Pathology and Therapy of the Academy of Sciences of Abkhazia;
Abkhazian State University;
2. Creator Author's name, affiliation, country Vladimir S. Barkaya; Research Institute of Experimental Pathology and Therapy of the Academy of Sciences of Abkhazia;
2. Creator Author's name, affiliation, country Zurab Ya. Mikvabiya; Research Institute of Experimental Pathology and Therapy of the Academy of Sciences of Abkhazia;
2. Creator Author's name, affiliation, country Gennadiy I. Karataev; Federal Research Centre for Epidemiology and Microbiology named after the honorary academician N.F. Gamaleya; Россия
3. Subject Discipline(s)
3. Subject Keyword(s) pertussis; live intranasal vaccine; protective activity; attenuated Bordetella pertussis bacteria; nonhuman primates
4. Description Abstract

Introduction. An increasing incidence of pertussis among different groups of population and shortcomings of the existing preventive solutions pinpoint urgency of development of new safe vaccines suitable for immunization of infants and for booster immunization of adolescents and adults.
The purpose of this study is evaluation of safety, immunogenicity and protective activity of the new constructed attenuated Bordetella pertussis bacteria 4MKS by infecting immunized Macaca mulatta monkeys intranasally with virulent bacteria of the pertussis pathogen.
Materials and methods. Five adult, clinically healthy Macaca mulatta monkeys aged 3–4 years were used for immunization and experimental infection. The re-immunization was performed in 6 months. Three non-immunized animals of the same age were used as controls.
Results. The intranasal single-dose inoculation and re-inoculation of attenuated B. pertussis bacteria did not cause any nasopharyngeal inflammation in the rhesus monkeys and any changes in the blood lab test values after the nonhuman primates had been infected with virulent bacteria. No elevation of total IgE was detected in blood serum of the Macaca mulatta monkeys after the single-dose and double-dose immunization. When the monkeys were intranasally immunized with attenuated and virulent B. pertussis bacteria, they developed a defensive reaction to re-infection, namely suppression of the bacterial growth, increased rates of elimination of bacteria from the animals’ nasopharynxes and development of a humoral immune response to the infection. The development of immunity against pertussis re-infection is accompanied by a pronounced booster effect.
Discussion. The obtained results suggest common mechanisms of development both of post-vaccination immunity after intranasal vaccination of animals and infection-acquired immunity against pertussis. Both of them provide protection against re-infection with B. pertussis bacteria and prevent development of clinical symptoms of pertussis.
5. Publisher Organizing agency, location Central Research Institute for Epidemiology
6. Contributor Sponsor(s)
7. Date (DD-MM-YYYY) 02.09.2020
8. Type Status & genre Peer-reviewed Article
8. Type Type Research Article
9. Format File format
10. Identifier Uniform Resource Identifier https://microbiol.crie.ru/jour/article/view/868
10. Identifier Digital Object Identifier (DOI) 10.36233/0372-9311-2020-97-4-3
11. Source Title; vol., no. (year) Journal of microbiology, epidemiology and immunobiology; Vol 97, No 4 (2020)
12. Language English=en ru
13. Relation Supp. Files Fig. 1. Changes in the number of BP genome-equivalents in the RMs' nasopharynx after the first and repeated intranasal vaccination with BP bacteria.N — the number of BP genome-equivalents in 1 ml of the nasopharyngeal aspirate. 1 — the first vaccination with virulent BP bacteria; 2 — the repeated vaccination with virulent BP bacteria; 3 — the first vaccination with attenuated BP bacteria; 4 — the repeated vaccination with attenuated BP bacteria; 5 — the infection with virulent BP bacteria 12 months after the vaccination with attenuated BP bacteria. (27KB)
Fig. 2. Changes in the number of BP 18323 genome-equivalents after the 1st and 2nd experimental intranasal infection of RMs.1 — the 1st experimental intranasal infection at a dose of 107 CFU; 2 — the 1st experimental intranasal infection at a dose of 109 CFU; 3 — repeated experimental infection with BP 18323 at a dose of 109-1010 CFU. (31KB)
Fig. 3. Changes in the IgG level in the RMs' blood serum after the 1st and repeated intranasal vaccination with BP bacteria.On the vertical axis — the relative value of IgG levels (%): ODC+/ODi, where ODC+ — optical density of the positive control, ODi — optical density in the well with the studied serum. 1 — the 1st vaccination with attenuated BP bacteria; 2 — the 1st vaccination with virulent BP bacteria; 3 — the infection with virulent BP bacteria 12 months after the vaccination with attenuated BP bacteria; 4 — the repeated vaccination with virulent BP bacteria; 5 — the repeated vaccination with attenuated BP bacteria. (16KB)
Fig. 4. Changes in the IgG relative levels in the RMs' blood serum after the 1st and repeated intranasal infection of the animals with Bp 18323 bacteria.1 — the 1st experimental intranasal infection at a dose of 107 CFU; 2 — the 1st experimental intranasal infection at a dose of 109 CFU; 3 — the repeated experimental infection with BP 18323 at a dose of 109 CFU. (14KB)
14. Coverage Geo-spatial location, chronological period, research sample (gender, age, etc.)
15. Rights Copyright and permissions Copyright (c) 2020 Medkova A.Y., Sinyashina L.N., Amichba A.A., Semin E.G., Shevtsova Z.V., Matua A.Z., Djidaryan A.A., Kubrava D.T., Kondzhariya I.G., Barkaya V.S., Mikvabiya Z.Y., Karataev G.I.
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