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

查看全文 作  者:Dina [1]Bugybayeva;Zhailaubay [1]Kydyrbayev;Nadezhda [1]Zinina;Nurika [1]Assanzhanova;Bolat [1]Yespembetov;Yerken [1]Kozhamkulov;Kunsulu [1]Zakarya;Sholpan [1]Ryskeldinova;Kaissar [2,3]Tabynov 高影响力作者 机构地区:[1]Research Institute for Biological Safety Problems,15 Momushuly,Gvardeyskiy 080409,Kazakhstan;[2]Kazakh National Agrarian University,8 Abay Avenue,Almaty 050010,Kazakhstan;[3]Research Institute of Cardiology and Internal Medicine,120 Aiteke bi,Almaty 050000,Kazakhstan.高影响力机构 出  处:《Infectious Diseases of Poverty》索引2021年第10卷第1期,共10页高影响力期刊 基  金:supported by the Science Committee of the Ministry of Education and Science of the Republic of Kazakhstan under Grant No.AP05131463. 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,Omp19or 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) EID50,10^(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 ft 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 vacci ne using conjunctival,intra nasal and subli ngual 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) EID50, which provides 80%protection of guinea pigs from B.melitensis 16 M infection(P<0.05),which is comparable to the results of the effectiv en ess of the commercial B.melitensis Rev.1 vacci ne.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. 关 键 词:Human brucellosis Influenza viral vectors Vaccine candidate Protection Guinea pigs Immunization route Vaccination dose
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