A new candidate vaccine for human brucellosis based on influenza viral vectors: a preliminary investigation for the development of an immunization schedule in a guinea pig model

• 作者: Bugybayeva Dina Kydyrbayev Zhailaubay Zinina Nadezhda Assanzhanova Nurika Yespembetov Bolat Kozhamkulov Yerken Zakarya Kunsulu Ryskeldinova Sholpan Tabynov Kaissar
• 来源期刊: 贫困所致传染病（英文）
• 关键词: Human brucellosis Influenza viral vectors Vaccine candidate Protection Guinea pigs Immunization route Vaccination dose
• 年，卷（期）: 2021,（1）
• 所属期刊栏目: Research Article
• 页码范围: 56-65
• 页数: 10页
• 语种: 中文
• DOI: 10.1186/s40249-021-00801-y

摘要

Background::A new candidate vector vaccine against human brucellosis based on recombinant influenza viral vectors (rIVV) subtypes H5N1 expressing Brucella outer membrane protein (Omp) 16, L7/L12, Omp19 or Cu-Zn SOD proteins has been developed. This paper presents the results of the study of protection of the vaccine using on guinea pigs, including various options of administering, dose and frequency. Provided data of the novel vaccine candidate will contribute to its further movement into the preclinical stage study. Methods::General states of guinea pigs was assessed based on behavior and dynamics of a guinea pig weight-gain test. The effectiveness of the new anti-brucellosis vector vaccine was determined by studying its protective effect after conjunctival, intranasal and sublingual administration in doses 10 5 EID 50, 10 6 EID 50 and 10 7 EID 50 during prime and boost vaccinations of animals, followed by challenge with a virulent strain of B. melitensis 16 M infection. For sake of comparison, the commercial B. melitensis Rev.1 vaccine was used as a control. The protective properties of vaccines were assessed by quantitation of Brucella colonization in organs and tissues of infected animals and compared to the control groups. Results::It was observed a gradual increase in body weight of guinea pigs after prime and booster immunization with the vaccine using conjunctival, intranasal and sublingual routes of administration, as well as after using various doses of vaccine. The most optimal way of using the vaccine has been established: double intranasal immunization of guinea pigs at a dose of 10 6 EID 50, which provides 80% protection of guinea pigs from B. melitensis 16 M infection ( P < 0.05), which is comparable to the results of the effectiveness of the commercial B. melitensis Rev.1 vaccine. Conclusions::We developed effective human vaccine candidate against brucellosis and developed its immunization protocol in guinea pig model. We believe that because of these studies, the proposed vaccine has achieved the best level of protection, which in turn provides a basis for its further promotion.