бешенство является зоонозной природно-очаговой инфекционной болезнью, общей для челове-ка и животных. ее абсолютная фатальность и эволю-ция придают чрезвычайный характер каждому случаю и ставят ветеринарно-медицинскую проблему бешен-ства в разряд первостепенных. ежегодная инцидент-ность регистрируемого в мире бешенства животных составляет от 30 до 45 тыс. [6]. количество людей, по-гибающих от гидрофобии, достигает 55 тыс. человек, из них 45 % случаев относится к региону Южной и Юго-восточной азии [20,21]. в российской Федерации на протяжении по- в статье представлены результаты изучения биопроб специалистами центра специальной лабораторной диа-гностики особо опасных и экзотических инфекционных болезней за период с 2002 по 2015 год, поступивших от погибших людей, подозрительных на инфицирование вирусом бешенства. освещены основные трудности при работе с поступившими пробами биологического материала от погибших людей и пути их преодоления. обозначены острые проблемы по бешенству эпизоотологической и эпидемиологической направленности, требую-щие комплексного решения со стороны органов здравоохранения и ветеринарной службы российской Федерации. подведены итоги лабораторно-диагностической работы центра специальной лабораторной диагностики особо опасных и экзотических инфекционных заболеваний. показано, что применяемые методы выделения и иденти-фикации возбудителя бешенства позволяют качественно и своевременно диагностировать данное заболевание.Ключевые слова: бешенство, уличный вирус бешенства, лабораторная диагностика. Scientific Center on Expertise of Medical Application Products, Moscow, Russian FederationThe article presents the results of bioassays investigation by the specialists of the Center for Special Laboratory Diagnostics of Particularly Dangerous and Exotic Infectious Diseases, isolated during 2002-2015, obtained from deceased people suspected for rabies virus infection. Outlined are the main challenges of working with the received samples of biological material from dead people and ways of handling these issues. Put forward are the pressing problems of epizootic and epidemiological bias that require comprehensive solutions on the part of healthcare authorities and the veterinary service of the Russian Federation. Given are the results of the laboratory-diagnostic activities of the Center for Special Laboratory Diagnostics of Particularly Dangerous and Exotic Infectious Diseases, which indicate that the applied methods of isolation and identification of the rabies pathogen allow for efficient and in-time diagnosis of the disease.

The review considers the relevant aspects of laboratory diagnosis of rabies. The methods of laboratory diagnostics of rabies infection, standardized by WHO in 2018, and their use in the Russian Federation are presented. The scheme of laboratory diagnostics of rabies, applied by specialists of the “48th CRI” of the Ministry of Defense of Russia, for the study of biological samples from deceased people is outlined. Between 2002 and 2018, the study of biomaterial was carried out using molecular-biological, virological methods of diagnosis and in some cases electron microscopy, which allowed to detect and identify the pathogen in 257 samples from 71 people, to certify and deposit new isolates of the rabies virus. Accumulation and analysis of the lessons learned in the application of molecular-biological method of rabies diagnosis allows us to recommend the use of RT-PCR, real-time RT-PCR sets (having a certificate of state registration) in healthcare and veterinary medicine practice to identify the causative agent of rabies infection. The use of molecular-biological methods is promising in terms of the development of rabies diagnosis to improve epidemiological surveillance and raise the efficiency of the biological protection of the population of the Russian Federation.

The review presents the results of preclinical use of vector vaccines against human immunodeficiency virus (HIV) disease and simian immunodeficiency virus (SIV) disease. Application of antiretroviral therapy exclusively is insufficient for elimination of HIV from patient’s body. This dictates the need for an effective vaccine which will reduce the number of new cases of the disease and reduce the risk of virus transmission. Current practice of medicinal product development showed the effectiveness of heterologous prime-boost regimens for the induction of expressed immune response in laboratory animals. Various vector constructs were used as priming vaccines: DNA vaccines, Bacille Calmette-Guerin vaccine, chimpanzee adenovirus, vesicular stomatitis virus, alphavirus repli-clone. Booster vaccine was represented by recombinant MVA strain. In all vector vaccines, different genes of immunodominant antigens of HIV and SIV agents were inserted. On rhesus macaques, murine, rabbit models, it was demonstrated that deployed vaccination schemes were safe and induced immune response. Because membrane HIV protein is highly variable, strongly glycoziled and subjected to structural changes during receptor binding, it cannot be viewed as a target for induction of virus neutralized antibodies. Therefore, we mainly studied the cell immune response that was presented by poly-functional CD8+ T-cells. However, some recent researches are aimed at such modification of envelope HIV immunogene that would provide for virus neutralizing antibody induction. The study of protective efficiency of the induced immunity in rhesus macaques, immunized with recombinant vectors expressing SIV’ s immunodominant antigens, in case of subsequent inoculation with virulent SIV strain has revealed that all monkeys developed illness. Assuming that the constructions with SIV’ s immunodominant antigens under protective efficiency testing on rhesus macaques imitate AIDS in humans, it seems that vaccines, developed up-to-date, will not be effective for collective immunity formation against AIDS. Therefore, the search for novel combinations of expressed immunodominant antigens for the inclusion into the composition of priming and booster vaccines remains a priority area at present time.

Although successes in antiretroviral therapy (ART) turned AIDS from lethal illness into sluggishly progressing disease, its prevention and treatment remain one of the most socially significant concerns. The increase in the number of patients infected with human immunodeficiency virus (HIV), especially in the USA, South America and Europe, determines the need in creating a vaccine against this disease. Existing vaccination practice has demonstrated efficiency of priming/boosting scheme for the development of immune responses. As anti-vector immunity of priming vector can constrain the response to boosting immunization with the same vaccine, heterologous priming/boosting vector constructs are used. An ideal AIDS vaccine would prevent virus dissemination and control viral replication, but it also must be safe for HIV-infected contingent. The vaccination of HIV-infected individuals is used for enhancing immune-mediated elimination of persistently HIV-infected CD4+ Т-cells during long-term ART in order to purge the latently infected viral reservoirs. The paper considers the results of clinical trials of DNA-anti-HIV/AIDS vaccines and recombinant MVA strain of vaccinia virus, expressing different combination of HIV genes, which demonstrated the safety and tolerability both, in HIV-infected and non-HIV-infected volunteers. All implemented schedules of vaccination induced cell-mediated and humoral immune responses in all volunteers. And though there are no data on acquiring AIDS by HIV-uninfected volunteers from groups at low risk of HIV-infection, there are no grounds to conclude the sufficiency of induced protection for the prevention of possible HIV infection.

Epidemic vector-borne viral infections pose a serious threat to public health worldwide. There is currently no specific preventive treatment for most of them. One of the promising solutions for combating viral fevers is development of vector vaccines, including MVA-based vaccines, which have virtually no adverse side effects. The safety of the MVA strain and absent reactogenicity of recombinant MVA vaccines have been supported by many clinical trials.The article focuses on test results for similar preventive products against viral fevers: Crimean-Congo hemorrhagic fever, Rift Valley fever, yellow fever, Chikungunya and Zika fevers.Their immunogenicity was evaluated on immunocompetent and immunocompromised white mice; their protective efficacy was assessed on immunocompromised white mice deficient in IFN-α/β receptors, that are used for experimental modeling of the infection. Nearly all the new recombinant vaccines expressing immunodominant antigens demonstrated 100% protective efficacy. It has been found that although the vaccine expressing Zika virus structural proteins induced antibodies against specific viral glycoproteins, it can be associated with high risks when used for prevention of Zika fever in individuals who had dengue fever in the past, due to the phenomenon known as antibody-dependent enhancement of infection, which can occur in diseases caused by antigenically related flaviruses. For this reason, the vaccine expressing non-structural protein 1 (NS1) was developed for vaccination against Zika fever.The yellow fever vaccine developed on the MVA platform had immunogenicity similar to that of the commercial 17D vaccine, outperforming the latter in safety.