Epizootic pertussis focus of hamadryad baboons

The absence of an adequate experimental animal model makes difficult study of immunity against whooping cough and its pathogenesis. Experimental whooping cough reported by us earlier in pubescent non-human primates of the Old World was accompanied by specific clinical and laboratory marks in the absence of cough. The possibility of pertussis modelling while experimental whooping cough in impuberal hamadryad baboons was investigated. In the process of selection of monkeys for the further studies for perfecting of experimental model for pertussis research unexpectedly were detected specific pertussis antibodies in impuberal hamadryad baboons.The aim of the study: revealing of source of infection and transmission of pertussis to hamadryad baboons and investigation of response of antibody-positive impuberal hamadryad baboons to secondary contagion by B. pertussis bacteria while experimental infection.Results. 18 veterinary checked, somatically healthy hamadryad baboons of various gender managed in two neighboring cages. Specific pertussis IgM and IgG antibodies were found in blood serum of all the animals and one of the monkey keepers. By real-time PCR in nasopharyngeal swabs of the monkey keeper and three 7- and 9-month-old hamadryad baboons were registered single B. pertussis genom equivalents. Seropositive impuberal hamadryad baboons were experimentally challenged by virulent B. pertussis 475 strain. Quantity of B. pertussis genom equivalents and percentage of IgM and IgG antibodies in impuberal hamadryad baboons after experimental infection were detected. These results were comparable with such received after secondary experimental challenge of monkeys by B. pertussis. Humoral immuneresponse was characterized by booster effect and rapid B. pertussis elimination.Conclusion. The case of transmission of B.pertussis bacteria to hamadryad baboons by natural contagion and epizootic focus of pertussis in apery conditions were registered. In dynamics of immune response and level of bacterial load in experimentally infected impuberal and pubescent hamadryad baboons were not revealed significant differences. The possibility of asymptomatic B.pertussis transmission from man to monkey and from monkey to man without definitive spasmodic cough was reviewed. Pertussis research perspectives using experimental model of non-human primates of the Old World were marked

Эпизоотический очаг коклюша у обезьян вида Papio gamadryas

The absence of an adequate experimental animal model makes difficult study of immunity against whooping cough and its pathogenesis. Experimental whooping cough reported by us earlier in pubescent non-human primates of the Old World was accompanied by specific clinical and laboratory marks in the absence of cough. The possibility of pertussis modelling while experimental whooping cough in impuberal hamadryad baboons was investigated. In the process of selection of monkeys for the further studies for perfecting of experimental model for pertussis research unexpectedly were detected specific pertussis antibodies in impuberal hamadryad baboons.The aim of the study: revealing of source of infection and transmission of pertussis to hamadryad baboons and investigation of response of antibody-positive impuberal hamadryad baboons to secondary contagion by B. pertussis bacteria while experimental infection.Results. 18 veterinary checked, somatically healthy hamadryad baboons of various gender managed in two neighboring cages. Specific pertussis IgM and IgG antibodies were found in blood serum of all the animals and one of the monkey keepers. By real-time PCR in nasopharyngeal swabs of the monkey keeper and three 7- and 9-month-old hamadryad baboons were registered single B. pertussis genom equivalents. Seropositive impuberal hamadryad baboons were experimentally challenged by virulent B. pertussis 475 strain. Quantity of B. pertussis genom equivalents and percentage of IgM and IgG antibodies in impuberal hamadryad baboons after experimental infection were detected. These results were comparable with such received after secondary experimental challenge of monkeys by B. pertussis. Humoral immuneresponse was characterized by booster effect and rapid B. pertussis elimination.Conclusion. The case of transmission of B.pertussis bacteria to hamadryad baboons by natural contagion and epizootic focus of pertussis in apery conditions were registered. In dynamics of immune response and level of bacterial load in experimentally infected impuberal and pubescent hamadryad baboons were not revealed significant differences. The possibility of asymptomatic B.pertussis transmission from man to monkey and from monkey to man without definitive spasmodic cough was reviewed. Pertussis research perspectives using experimental model of non-human primates of the Old World were marked.Введение. Изучение патогенеза и иммунитета при коклюше затруднено в связи с отсутствием адекватной экспериментальной модели. Описанный нами ранее экспериментальный коклюш у половозрелых обезьян Старого Света сопровождался развитием характерных клинико-лабораторных признаков коклюша при отсутствии кашля. В процессе отбора обезьян для дальнейшей работы по совершенствованию экспериментальной модели для изучения коклюша у неполовозрелых павианов гамадрилов неожиданно были обнаруженыспецифические противококлюшные антитела.Цель. Выявление источника бактерий В. рertussis и пути их передачи павианам гамадрилам, а также изучение реакции организма серопозитивных неполовозрелых павианов на вторичный контакт с возбудителем коклюша при экспериментальном заражении. Результаты. 18 обследованных павианов гамадрилов разного пола, размещённые в двух соседних вольерных клетках, находились в состоянии соматического здоровья. В сыворотке крови всех животных и одного из сотрудников по уходу за животными были выявлены специфические антитела класса IgG и IgМ к возбудителю коклюша. Методом ПЦР в режиме реального времени из материала назофарингеальных мазков зарегистрированы единичные геном-эквиваленты B. pertussis у рабочего по уходу за животными и трёх павианов гамадрилов в возрасте 7–9 месяцев. Серопозитивные неполовозрелые павианы гамадрилы были экспериментально заражены вирулентными бактериями B. pertussis 475. Результаты определения количества геном-эквивалентов B. pertussis и относительного количества специфических IgG и IgМ у неполовозрелых павианов гамадрилов после экспериментального заражения были сопоставимы с таковыми у взрослых, дважды инфицированных обезьян. Гуморальный иммунный ответ характеризовался бустерным эффектом с быстрой элиминацией возбудителя. Заключение. Зарегистрирован случай передачи бактерий B. pertussis павианам гамадрилам естественным путем и эпизоотический очаг коклюша в условиях питомника. Не выявлено значимых различий в динамике развития иммунного ответа и бактериальной нагрузки у экспериментально инфицированных неполовозрелых и половозрелых павианов гамадрилов. Показана возможность передачи бактерий B. pertussis без характерного коклюшного кашля от человека к обезьяне и от обезьяны к обезьяне. Описаны перспективы изучения коклюша на экспериментальной модели обезьян Старого Света

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

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