Immunogenicity of HIV-1 Env mRNA and Env-Gag VLP mRNA Vaccines in Mice.

IF 5.2 3区医学 Q1 IMMUNOLOGY

Vaccines Pub Date : 2025-01-17 DOI:10.3390/vaccines13010084

Qi Ma, Jing Yang, Xiaoguang Zhang, Hongxia Li, Yanzhe Hao, Xia Feng

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Abstract

Background: The development of a protective vaccine is critical for conclusively ending the human immunodeficiency virus (HIV) epidemic.

Methods: We constructed nucleotide-modified mRNA vaccines expressing HIV-1 Env and Gag proteins. Env-gag virus-like particles (VLPs) were generated through co-transfection with env and gag mRNA vaccines. BALB/c mice were immunized with env mRNA, env-gag VLP mRNA, env plasmid DNA vaccine, or lipid nanoparticle (LNP) controls. HIV Env-specific binding and neutralizing antibodies in mouse sera were assessed via enzyme-linked immunosorbent assay (ELISA) and pseudovirus-based neutralization assays, respectively. Env-specific cellular immune responses in mouse splenocytes were evaluated using an Enzyme-linked immunosorbent assay (ELISpot) and in vivo cytotoxic T cell-killing assays.

Results: The Env-specific humoral and cellular immune responses elicited by HIV-1 env mRNA and env-gag VLP mRNA vaccine were stronger than those induced by the DNA vaccine. Specific immune responses induced by the env mRNA vaccine were significantly stronger in the high-dose group than in the low-dose group. Immunization with co-formulated env and gag mRNAs elicited superior cellular immune responses compared to env mRNA alone.

Conclusions: These findings suggest that the env-gag VLP mRNA platform holds significant promise for HIV-1 vaccine development.

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背景：开发保护性疫苗对于彻底终止人类免疫缺陷病毒（HIV）流行至关重要：方法：我们构建了表达 HIV-1 Env 和 Gag 蛋白的核苷酸修饰 mRNA 疫苗：我们构建了表达 HIV-1 Env 和 Gag 蛋白的核苷酸修饰 mRNA 疫苗。方法：我们构建了表达 HIV-1 Env 和 Gag 蛋白的核苷酸修饰 mRNA 疫苗，并通过与 env 和 gag mRNA 疫苗共转染生成 Env-gag 病毒样颗粒（VLPs）。用 env mRNA、env-gag VLP mRNA、env 质粒 DNA 疫苗或脂质纳米颗粒 (LNP) 对照组对 BALB/c 小鼠进行免疫。小鼠血清中的 HIV Env 特异性结合抗体和中和抗体分别通过酶联免疫吸附试验（ELISA）和基于假病毒的中和试验进行了评估。使用酶联免疫吸附试验（ELISpot）和体内细胞毒性T细胞杀伤试验评估了小鼠脾细胞中的Env特异性细胞免疫反应：结果：HIV-1 env mRNA和env-gag VLP mRNA疫苗诱导的Env特异性体液和细胞免疫反应强于DNA疫苗。env mRNA疫苗诱导的特异性免疫反应在高剂量组明显强于低剂量组。与单独接种 env mRNA 相比，共同配制的 env 和 gag mRNA 疫苗能诱导更强的细胞免疫反应：这些研究结果表明，env-gag VLP mRNA 平台在开发 HIV-1 疫苗方面大有可为。

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来源期刊

Vaccines Pharmacology, Toxicology and Pharmaceutics-Pharmacology

CiteScore

8.90

自引率

16.70%

发文量

1853

审稿时长

18.06 days

期刊介绍： Vaccines (ISSN 2076-393X) is an international, peer-reviewed open access journal focused on laboratory and clinical vaccine research, utilization and immunization. Vaccines publishes high quality reviews, regular research papers, communications and case reports.