[Immunization of Mice with the pVAXrbd DNA Vaccine by Jet Injection Induces a Stronger Immune Response and Protection against SARS-CoV-2 Compared to Intramuscular Injection by Syringe].

Q3 Medicine
D N Kisakov, M B Borgoyakova, L A Kisakova, E V Starostina, O V Pyankov, A V Zaykovskaya, O S Taranov, E K Ivleva, N B Rudometova, V A Yakovlev, E V Tigeeva, M Sh Azaev, I M Belyakov, A P Rudometov, A A Ilyichev, L I Karpenko
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引用次数: 0

Abstract

During the COVID-19 pandemic, it became clear that, to ensure global health security, it is essential to have a developed platform that can be used to develop a safe, low-cost, effective vaccine quickly. DNA vaccines have several advantages over other platforms, including rapid development and ease of production. They are more stable than mRNA vaccines. Unlike viral vector-based vaccines, DNA vaccines do not induce antivector immunity. One of the disadvantages of DNA vaccines is their relatively low immunogenicity. This problem can be solved using jet injection. Here, we evaluated and confirmed the efficiency of an inexpensive, simple, and safe method for delivering the naked DNA vaccine pVAXrbd encoding the receptor-binding domain (RBD) of the SARS-CoV-2 spike (S) protein using a spring-loaded jet injector. Based on the results of histological analysis, optimal conditions were determined that ensure low tissue trauma in laboratory animals upon administration of pVAXrbd. An optimized immunization protocol for BALB/c mice was used to compare the immunogenicity of pVAXrbd with two different administration schemes: using a jet injector under the skin and into the adjacent muscle layers or intramuscularly using a syringe with a needle. Mice immunized with "naked" pVAX-RBD were shown to produce high levels of specific virus-neutralizing antibodies. The vaccine also induced a strong RBD-specific T-cell response. As shown by quantitative PCR analysis of viral RNA, vaccinated mice infected with the Gamma variant of SARS-CoV-2 developed a protective immune response; moreover, it was more pronounced in animals to which the DNA-vaccine was administered using a jet injector compared to those immunized intramuscularly. Thus, the introduction of a DNA-vaccine using jet injection effectively activates both types of immune response and leads to a decrease in the viral load. Jet injection is a promising method for delivering DNA vaccines, characterized by low cost, simplicity, technological administration, and minimal pain for the patient.

[喷射注射pVAXrbd DNA疫苗免疫小鼠比肌肉注射更强的免疫反应和对SARS-CoV-2的保护作用]。
在2019冠状病毒病大流行期间,很明显,为了确保全球卫生安全,必须拥有一个发达的平台,可用于快速开发安全、低成本、有效的疫苗。与其他平台相比,DNA疫苗有几个优势,包括快速开发和易于生产。它们比mRNA疫苗更稳定。与基于病毒载体的疫苗不同,DNA疫苗不诱导抗载体免疫。DNA疫苗的缺点之一是免疫原性相对较低。这个问题可以用喷射法解决。在这里,我们评估并确认了一种廉价、简单、安全的方法,用于使用弹簧负载的喷射注射器递送编码SARS-CoV-2刺突蛋白受体结合域(RBD)的裸DNA疫苗pVAXrbd的效率。根据组织学分析结果,确定了pVAXrbd给药后实验动物低组织损伤的最佳条件。采用优化的BALB/c小鼠免疫方案,比较pVAXrbd在两种不同给药方案下的免疫原性:皮下注射和邻近肌肉层注射或用带针的注射器肌肉注射。用“裸”pVAX-RBD免疫的小鼠显示产生高水平的特异性病毒中和抗体。该疫苗还诱导了强烈的rbd特异性t细胞反应。病毒RNA的定量PCR分析表明,接种了SARS-CoV-2 γ变体疫苗的小鼠产生了保护性免疫反应;此外,在使用喷射注射器注射dna疫苗的动物中,与肌肉注射免疫的动物相比,这种情况更为明显。因此,使用喷射注射的dna疫苗的引入有效地激活了两种类型的免疫反应,并导致病毒载量的减少。喷射注射是一种很有前途的DNA疫苗注射方法,其特点是成本低,操作简单,技术管理,对患者的痛苦最小。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Molekulyarnaya Biologiya
Molekulyarnaya Biologiya Medicine-Medicine (all)
CiteScore
0.70
自引率
0.00%
发文量
131
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