Enhancing Immune Responses to a DNA Vaccine Encoding Toxoplasma gondii GRA7 Using Calcium Phosphate Nanoparticles as an Adjuvant.

Enhancing Immune Responses to a DNA Vaccine Encoding Toxoplasma gondii GRA7 Using Calcium Phosphate Nanoparticles as an Adjuvant.
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使用磷酸钙纳米粒子作为佐剂增强编码弓形虫 GRA7 的 DNA 疫苗的免疫反应

DOI:
10.3389/fcimb.2021.787635
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发表时间:
2021
影响因子:
5.7
通讯作者:
Shi TY
Shi TY
中科院分区:
医学2区
文献类型:
--
作者:
Sun HC;Huang J;Fu Y;Hao LL;Liu X;Shi TY

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弓形虫感染几乎所有温血动物,包括人类。 DNA疫苗是对抗弓形虫感染的有效策略,但由于质粒分布不良或被溶酶体降解,这些疫苗往往免疫原性较差。有必要评估抗原递送系统以获得最佳疫苗接种策略。纳米颗粒(NP)已被证明可以调节和增强细胞体液免疫反应。在这里,我们研究了磷酸钙纳米颗粒(CaPNs)作为纳米佐剂的免疫学特性,以增强弓形虫致密颗粒蛋白(GRA7)的保护作用。 BALB/c小鼠注射3次,然后用弓形虫RH株速殖子攻击。通过抗 T 细胞水平升高监测,接种 GRA7-pEGFP-C2+ 纳米佐剂 (CaPN) 的小鼠表现出强烈的细胞免疫反应。弓形虫特异性免疫球蛋白 G (IgG)、较高的 IgG2a 与 IgG1 比率、升高的白细胞介素 (IL)-12 和干扰素 (IFN)-γ 产生以及较低的 IL-4 水平。我们发现,GRA7-pEGFP-C2+纳米佐剂(CaPNs)免疫诱导了显着更高水平的脾细胞增殖,并且在疫苗免疫的小鼠中观察到显着延长的存活时间和减少的寄生虫负担。这些数据表明,基于 CaPN 的弓形虫 GRA7 免疫是改善疫苗接种的一种有前途的方法。
Toxoplasma gondii infects almost all warm-blooded animals, including humans. DNA vaccines are an effective strategy against T. gondii infection, but these vaccines have often been poorly immunogenic due to the poor distribution of plasmids or degradation by lysosomes. It is necessary to evaluate the antigen delivery system for optimal vaccination strategy. Nanoparticles (NPs) have been shown to modulate and enhance the cellular humoral immune response. Here, we studied the immunological properties of calcium phosphate nanoparticles (CaPNs) as nanoadjuvants to enhance the protective effect of T. gondii dense granule protein (GRA7). BALB/c mice were injected three times and then challenged with T. gondii RH strain tachyzoites. Mice vaccinated with GRA7-pEGFP-C2+nano-adjuvant (CaPNs) showed a strong cellular immune response, as monitored by elevated levels of anti-T. gondii-specific immunoglobulin G (IgG), a higher IgG2a-to-IgG1 ratio, elevated interleukin (IL)-12 and interferon (IFN)-γ production, and low IL-4 levels. We found that a significantly higher level of splenocyte proliferation was induced by GRA7-pEGFP-C2+nano-adjuvant (CaPNs) immunization, and a significantly prolonged survival time and decreased parasite burden were observed in vaccine-immunized mice. These data indicated that CaPN-based immunization with T. gondii GRA7 is a promising approach to improve vaccination.
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