Khan Masood Alam, Khan Arif, Alzohairy Mohammad A, Alruwetei Abdulmohsen M, Alsahli Mohammed A, Allemailem Khaled S, Alrumaihi Faris, Almatroudi Ahmad, Alhatlani Bader Y, Rugaie Osamah Al, Malik Ajamaluddin
Department of Basic Health Sciences, College of Applied Medical Sciences, Qassim University, Buraydah, Saudi Arabia.
Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Buraydah, Saudi Arabia.
J King Saud Univ Sci. 2022 Jul;34(5):102124. doi: 10.1016/j.jksus.2022.102124. Epub 2022 May 27.
Here, we prepared a liposome-based vaccine formulation containing Middle East Respiratory Syndrome Coronavirus papain-like protease (MERS-CoV-PLpro).
A persistent leukopenic condition was induced in mice by injecting cyclophosphamide (CYP) three days before each dose of immunization. Mice were immunized on days 0, 14 and 21 with α-GalCer-bearing MERS-CoV PLpro-encapsulated DPPC-liposomes (α-GalCer-MERS-PLpro-liposomes or MERS-CoV PLpo-encapsulated DPPC-liposomes (MERS-PLpro-liposomes), whereas the antigen emulsified in Alum (MERS-PLpro-Alum) was taken as a control. On day 26, the blood was taken from the immunized mice to analyze IgG titer, whereas the splenocytes were used to analyze the lymphocyte proliferation and the level of cytokines. In order to assess the memory immune response, mice were given a booster dose after 150 days of the last immunization.
The higher levels of MERS-CoV-PLpro-specific antibody titer, IgG2a and lymphocyte proliferation were noticed in mice immunized with α-GalCer-MERS-PLpro-liposomes. Besides, the splenocytes from mice immunized with α-GalCer-MERS-PLpro-liposomes produced larger amounts of IFN-γ as compared to the splenocytes from MERS-PLpro-liposomes or MERS- PLpro-Alum immunized mice. Importantly, an efficient antigen-specific memory immune response was observed in α-GalCer-MERS-PLpro-liposomes immunized mice.
These findings suggest that α-GalCer-MERS-PLpro-liposomes may substantiate to be a successful vaccine formulation against MERS-CoV infection, particularly in immunocompromised individuals.
在此,我们制备了一种基于脂质体的疫苗制剂,其包含中东呼吸综合征冠状病毒木瓜样蛋白酶(MERS-CoV-PLpro)。
在每次免疫前三天,通过注射环磷酰胺(CYP)在小鼠中诱导持续性白细胞减少症。在第0、14和21天,用负载α-半乳糖神经酰胺的包裹MERS-CoV PLpro的二棕榈酰磷脂酰胆碱脂质体(α-GalCer-MERS-PLpro-脂质体)或包裹MERS-CoV PLpo的二棕榈酰磷脂酰胆碱脂质体(MERS-PLpro-脂质体)对小鼠进行免疫,而以明矾乳化的抗原(MERS-PLpro-明矾)作为对照。在第26天,从免疫的小鼠中采集血液以分析IgG滴度,而脾细胞用于分析淋巴细胞增殖和细胞因子水平。为了评估记忆免疫反应,在最后一次免疫150天后给小鼠加强剂量。
在用α-GalCer-MERS-PLpro-脂质体免疫的小鼠中,观察到更高水平的MERS-CoV-PLpro特异性抗体滴度、IgG2a和淋巴细胞增殖。此外,与用MERS-PLpro-脂质体或MERS-PLpro-明矾免疫的小鼠的脾细胞相比,用α-GalCer-MERS-PLpro-脂质体免疫的小鼠的脾细胞产生了更多的干扰素-γ。重要的是,在α-GalCer-MERS-PLpro-脂质体免疫的小鼠中观察到了有效的抗原特异性记忆免疫反应。
这些发现表明,α-GalCer-MERS-PLpro-脂质体可能被证实是一种针对MERS-CoV感染的成功疫苗制剂,特别是在免疫功能低下的个体中。