Comprehensive Immunological Study of Persons Vaccinated with Live Plague Vaccine Living on the Territory of the Pre-Caspian Sand Foci of the Plague in the Republic of Kalmykia
ЭКСПЕРИМЕНТАЛЬНЫЙ ПРЕПАРАТ дЛя СПЕцИфИчЕСКоЙ ПРофИЛАКТИКИ ТУЛяРЕМИИ
ФКУЗ «Российский научно-исследовательский противочумный институт «Микроб», Саратов, Российская ФедерацияСконструирован экспериментальный препарат прототипной химической туляремийной вакцины (ПХТВ). В состав ПХТВ входит протективный антигенный комплекс (ПАК) туляремийного микроба и белок S-слоя (Slp) чумного микроба. Определено оптимальное соотношение компонентов и схема введения препарата. Представлены результаты испытаний его физико-химических свойств, реактогенности, специфической активности и влияния на иммунную систему лабораторных животных. Установлено, что препарат прототипа химической туляремийной вакцины не токсичен для белых мышей и морских свинок и не оказывает повреждающего действия на их иммунную систему. Однократная подкожная иммунизация лабораторных животных препаратом ПХТВ вызывает формирование напряженного адаптивного иммунитета к 14-21-м суткам: выработку специфических антител и стимуляцию клеточного звена иммунитета. Индекс защиты препарата ПХТВ для белых мышей при экспериментальной туляремии, вызванной Francisella tularensis subsp. holarctica, составил в среднем 87,5 %, при инфицировании F. tularensis subsp. nearctica -50 %, с высокой напряженностью иммунитета в обоих случаях. На модели морских свинок была подтверждена высокая эффективность экспериментального препарата против туляремии голарктического подвида (индекс защиты 75 %) и длительность напряженного иммунитета.
Ключевые слова: Francisella tularensis, антиген, химические вакцины.Designed is an experimental preparation of a prototype chemical tularemia vaccine (PCTV). It is composed of protective antigenic complex (PAC) of tularemia microbe and S-layer protein (Slp) of plague microbe. Determined is optimum ratio of these components in the preparation and schedule of its administration. Displayed are the results of its testing as regards physical-chemical properties, reactogenicity, specific activity and impact on the immune system of laboratory animals. It is found out that preparation of the prototype is non-toxic for white mice and Guinea pigs and has no damaging effect on their immune systems. Single-stage subcutaneous immunization with PCTV induces elaboration of high-level adaptive immunity in laboratory animals within 14-21 days: specific antibody generation and stimulation of immune system cell component. PCTV protective index for white mice in case of experimental tularemia, caused by Francisella tularensis subsp. holarctica, is 87,5 % on average; in case of infecting with F. tularensis subsp. nearctica -50 %; and high-level immunity in both cases. High potency of the experimental preparation against tularemia caused by subsp. holarctica (protective index is 75 %) and high-grade immunity persistence is verified on the model of Guinea pigs too.
To provide better opportunities for managing both risks caused by vaccination and risks of epidemiological complications, immunologic monitoring over people vaccinated with live dried plague vaccine (LPV) due to epidemiologic indications was performed. Our research goal was to assess whether immunologic monitoring over people vaccinated against plague yielded informative results; it was done to substantiate activities aimed at improving procedures for LPV application. Immunologic monitoring was performed from 2016 to 2019 in the Caspian sand natural plague focus according to conventional procedures for assessing humoral and cellular components in immunity. We determined immunologic parameters in 217 volunteers vaccinated with LPV and 130 healthy donors (the reference group) prior to and 1 and 12 months after vaccination. We suggested a methodical approach based on aggregated analysis of the summated immune response predictors chosen for estimation in volunteers vaccinated with LPV and giving score values to them; it allows revealing people who react to plague microbe antigens predominantly as per cellular, humoral, or mixed type. Immunologic monitoring results proved that it was safe to apply LPV; they allowed characterizing trends occurring in immunological restructuring in vaccinated volunteers, determining limits of fluctuation in individual parameters of an immune response to the vaccine, and revealing people with both normal and changed (reduced or increased) immunologic reactivity to LPV. If monitoring data are taken into account, it provides an opportunity to predict vaccination results as per epidemiological parameters, to reveal groups with normal, high, or low immune reactivity to plague microbe antigens in order to determine people in them who need an individual approach when it comes down to anti-plague vaccination.
Carried out was immunobiological evaluation of cholera toxin B subunit preparations obtained using different experimental and production methods. It was demonstrated that B subunit preparations were non-toxic for biomodels and did not cause significant pathological alterations in their organs and tissues. They also did not alter the condition of immunocompetent cells at different stages of their cycle, and promote anti-toxic antibodies production. Thus, B subunit preparations under study can be considered as promising components of cholera vaccine.
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