Lipid Nanoparticle Acts as a Potential Adjuvant for Influenza Split Vaccine without Inducing Inflammatory Responses.

Lipid Nanoparticle Acts as a Potential Adjuvant for Influenza Split Vaccine without Inducing Inflammatory Responses.
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DOI:
10.3390/vaccines8030433
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发表时间:
2020-08-03
期刊:
影响因子:
7.8
通讯作者:
Yoshioka Y
Yoshioka Y
中科院分区:
医学3区
文献类型:
--
作者:
Shirai S;Kawai A;Shibuya M;Munakata L;Omata D;Suzuki R;Yoshioka Y

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接种疫苗是控制流感病毒在人群中传播的关键和可靠的战略。与灭活全病毒疫苗等其他类型的疫苗相比,传统的流感季节性裂解疫苗(SVS)引起的免疫反应较弱,尽管与其他类型的疫苗相比,SVS具有很高的安全性。在这里,我们评估了我们开发的脂质纳米颗粒(LNP)作为传统流感病毒佐剂作为抗原在小鼠身上的潜力。LNP体外不能诱导树突状细胞产生IL-6、IL-12p40等细胞因子,也不能诱导树突状细胞表面共刺激分子的表达。相反,与单独使用SV相比,添加LNP的SV可改善SV特异性的IgG1和IgG2应答以及Th1应答。此外,佐剂LNP的SV对流感病毒的攻击具有比单独的SV更好的保护作用,并且与佐剂铝盐的SV在小鼠中的效果相同。LNP不能引起小鼠炎症反应,如炎性细胞因子的产生和炎性免疫细胞的浸润,而铝盐则能诱导炎症反应。这些结果表明,LNP作为一种没有炎症反应的佐剂对流感SVS具有潜在的作用。我们的策略应该有助于开发更有效和更安全的流感疫苗。
Vaccination is a critical and reliable strategy for controlling the spread of influenza viruses in populations. Conventional seasonal split vaccines (SVs) for influenza evoke weaker immune responses than other types of vaccines, such as inactivated whole-virion vaccines, although SVs are highly safe compared to other types. Here, we assessed the potential of the lipid nanoparticle (LNP) we developed as an adjuvant for conventional influenza SV as an antigen in mice. The LNP did not induce the production of cytokines such as interleukin-6 (IL-6) and IL-12 p40 by dendritic cells or the expression of co-stimulatory molecules on these cells in vitro. In contrast, an SV adjuvanted with LNP improved SV-specific IgG1 and IgG2 responses and the Th1 response compared to the SV alone in mice. In addition, SV adjuvanted with an LNP gave superior protection against the influenza virus challenge over the SV alone and was as effective as SV adjuvanted with aluminum salts in mice. The LNP did not provoke inflammatory responses such as inflammatory cytokine production and inflammatory immune cell infiltration in mice, whereas aluminum salts induced inflammatory responses. These results suggest the potential of the LNP as an adjuvant without inflammatory responses for influenza SVs. Our strategy should be useful for developing influenza vaccines with enhanced efficacy and safety.
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