Kisakov D N, Borgoyakova M B, Kisakova L A, Starostina E V, Pyankov O V, Zaykovskaya A V, Taranov O S, Ivleva E K, Rudometova N B, Yakovlev V A, Tigeeva E V, Azaev M Sh, Belyakov I M, Rudometov A P, Ilyichev A A, Karpenko L I
Vector State Scientific Center of Virology and Biotechnology Vector, Rospotrebnadzor, Center for Genomic Research of the World Level of Biosafety and Technological Independence, Federal Scientific and Technical Program for Development of Genetic Technologies, Koltsovo, Novosibirsk oblast, 630559 Russia.
Moscow Synergy Financial-Industrial University, Moscow, 129090 Russia.
Mol Biol (Mosk). 2025 May-Jun;59(3):453-468.
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.
在新冠疫情期间，很明显，为确保全球卫生安全，拥有一个可用于快速研发安全、低成本、有效疫苗的成熟平台至关重要。与其他平台相比，DNA疫苗具有多个优势，包括研发迅速和易于生产。它们比mRNA疫苗更稳定。与基于病毒载体的疫苗不同，DNA疫苗不会诱导抗载体免疫。DNA疫苗的一个缺点是其免疫原性相对较低。这个问题可以通过喷射注射来解决。在此，我们评估并证实了一种使用弹簧式喷射注射器递送编码严重急性呼吸综合征冠状病毒2（SARS-CoV-2）刺突（S）蛋白受体结合域（RBD）的裸DNA疫苗pVAXrbd的廉价、简单且安全方法的有效性。基于组织学分析结果，确定了在给予pVAXrbd时确保实验动物低组织创伤的最佳条件。使用针对BALB/c小鼠的优化免疫方案，比较了pVAXrbd在两种不同给药方案下的免疫原性：通过喷射注射器皮下注射并注入相邻肌肉层，或使用带针头的注射器进行肌肉注射。结果显示，用“裸”pVAX-RBD免疫的小鼠产生了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。如对病毒RNA的定量PCR分析所示，接种了SARS-CoV-2伽马变异株的疫苗接种小鼠产生了保护性免疫反应；此外，与肌肉注射免疫的动物相比，使用喷射注射器给予DNA疫苗的动物的免疫反应更明显。因此，通过喷射注射引入DNA疫苗可有效激活两种免疫反应并导致病毒载量降低。喷射注射是一种很有前景的DNA疫苗递送方法，其特点是成本低、操作简单、技术给药且患者痛苦最小。
Int J Nanomedicine. 2025-8-6
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