基于流感病毒载体的人类布鲁氏菌病新型候选疫苗：豚鼠模型中免疫方案开发的初步研究。

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.

机构信息

Research Institute for Biological Safety Problems, 15 Momushuly, Gvardeyskiy, 080409, Kazakhstan.

Kazakh National Agrarian University, 8 Abay Avenue, Almaty, 050010, Kazakhstan.

出版信息

Infect Dis Poverty. 2021 Feb 16;10(1):13. doi: 10.1186/s40249-021-00801-y.

DOI:10.1186/s40249-021-00801-y

PMID:33593447

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7886305/

Abstract

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 EID, 10 EID and 10 EID 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 EID, 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.

摘要

背景

一种基于重组流感病毒载体（rIVV）亚型 H5N1 的新型人布鲁氏菌候选疫苗向量已被开发出来，该载体表达布鲁氏菌外膜蛋白（Omp）16、L7/L12、Omp19 或 Cu-Zn SOD 蛋白。本文介绍了该疫苗在豚鼠中的保护作用研究结果，包括不同的给药途径、剂量和频率选择。提供的新型候选疫苗数据将有助于其进一步进入临床前研究阶段。

方法

根据豚鼠的行为和体重增长试验的动态来评估其一般状态。通过研究结膜、鼻腔和舌下给药的免疫原性和加强免疫后，使用 10 EID、10 EID 和 10 EID 剂量对动物进行免疫，然后用强毒 16M 感染攻击，来确定新型抗布鲁氏菌载体疫苗的有效性。为了进行比较，使用商业的 Rev.1 布鲁氏菌疫苗作为对照。通过定量分析感染动物器官和组织中的布鲁氏菌定植来评估疫苗的保护特性，并与对照组进行比较。