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四价狂犬病病毒载体丝状病毒和拉萨热疫苗可诱导非人灵长类动物产生长期免疫。

Tetravalent Rabies-Vectored Filovirus and Lassa Fever Vaccine Induces Long-term Immunity in Nonhuman Primates.

机构信息

Department of Microbiology and Immunology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.

AlphaGenesis Inc, Yemassee, South Carolina, USA.

出版信息

J Infect Dis. 2021 Sep 17;224(6):995-1004. doi: 10.1093/infdis/jiab014.

Abstract

BACKGROUND

The objective of this study is to evaluate the immunogenicity of adjuvanted monovalent rabies virus (RABV)-based vaccine candidates against Ebola virus (FILORAB1), Sudan virus (FILORAB2), Marburg virus (FILORAB3), Lassa virus (LASSARAB1), and combined trivalent vaccine candidate (FILORAB1-3) and tetravalent vaccine candidate (FILORAB1-3 and LASSARAB) in nonhuman primates.

METHODS

Twenty-four Macaca fascicularis were randomly assigned into 6 groups of 4 animals. Each group was vaccinated with either a single adjuvanted vaccine, the trivalent vaccine, or the tetravalent vaccine at days 0 and 28. We followed the humoral immune responses for 1 year by antigen-specific enzyme-linked immunosorbent assays and RABV neutralization assays.

RESULTS

High titers of filovirus and/or Lassa virus glycoprotein-specific immunoglobulin G were induced in the vaccinated animals. There were no significant differences between immune responses in animals vaccinated with single vaccines vs trivalent or tetravalent vaccines. In addition, all vaccine groups elicited strong rabies neutralizing antibody titers. The antigen-specific immune responses were detectable for 1 year in all groups.

CONCLUSIONS

In summary, this study shows the longevity of the immune responses up to 365 days for a pentavalent vaccine-against Ebola virus, Sudan virus, Marburg virus, Lassa virus, and RABV-using a safe and effective vaccine platform.

摘要

背景

本研究旨在评估含佐剂的单价狂犬病病毒(RABV)疫苗候选物对埃博拉病毒(FILORAB1)、苏丹病毒(FILORAB2)、马尔堡病毒(FILORAB3)、拉萨热病毒(LASSARAB1)以及单价、三价和四价联合疫苗候选物(FILORAB1-3 和 FILORAB1-3 和 LASSARAB)在非人灵长类动物中的免疫原性。

方法

24 只食蟹猴随机分为 6 组,每组 4 只。每组动物分别在第 0 天和第 28 天接种单价疫苗、三价疫苗或四价疫苗。通过抗原特异性酶联免疫吸附试验和 RABV 中和试验,我们在 1 年内对体液免疫反应进行了跟踪。

结果

接种疫苗的动物中诱导出了高滴度的丝状病毒和/或拉萨热病毒糖蛋白特异性免疫球蛋白 G。与单价疫苗相比,接种单价疫苗与三价或四价疫苗的动物的免疫反应没有显著差异。此外,所有疫苗组均诱导出了强烈的狂犬病中和抗体滴度。所有组的抗原特异性免疫反应在 1 年内均可检测到。

结论

总之,本研究表明,在使用安全有效的疫苗平台的情况下,五价疫苗——针对埃博拉病毒、苏丹病毒、马尔堡病毒、拉萨热病毒和 RABV——可诱导长达 365 天的免疫反应。

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