PDF(Pubmed)
Abstract：
Adjuvants are effective tools to enhance vaccine efficacy and control the type of immune responses such as antibody and T helper 1 (Th1)- or Th2-type responses. Several studies suggest that interferon (IFN)-γ-producing Th1 cells play a significant role against infections caused by intracellular bacteria and viruses; however, only a few adjuvants can induce a strong Th1-type immune response. Recently, several studies have shown that lipid nanoparticles (LNPs) can be used as vaccine adjuvants and that each LNP has a different adjuvant activity. In this study, we screened LNPs to develop an adjuvant that can induce Th1 cells and antibodies using a conventional influenza split vaccine (SV) as an antigen in mice. We observed that LNP with 1,2-di-O-octadecenyl-3-trimethylammonium-propane (DOTMA) as a component lipid (DOTMA-LNP) elicited robust SV-specific IgG1 and IgG2 responses compared with SV alone in mice and was as efficient as SV adjuvanted with other adjuvants in mice. Furthermore, DOTMA-LNPs induced robust IFN-γ-producing Th1 cells without inflammatory responses compared to those of other adjuvants, which conferred strong cross-protection in mice. We also demonstrated the high versatility of DOTMA-LNP as a Th1 cell-inducing vaccine adjuvant using vaccine antigens derived from severe acute respiratory syndrome coronavirus 2 and Streptococcus pneumoniae. Our findings suggest the potential of DOTMA-LNP as a safe and effective Th1 cell-inducing adjuvant and show that LNP formulations are potentially potent adjuvants to enhance the effectiveness of other subunit vaccines.
摘要：
佐剂是增强疫苗效力和控制免疫应答类型如抗体和T辅助1(Th1)-或Th2-型应答的有效工具。一些研究表明，产生干扰素（IFN）-γ的Th1细胞对由细胞内细菌和病毒引起的感染具有重要作用；然而，只有少数佐剂可以诱导强烈的Th1型免疫应答。最近,一些研究表明,脂质纳米颗粒(LNP)可以用作疫苗佐剂,并且每个LNP具有不同的佐剂活性。在这项研究中,我们筛选了LNP以开发一种佐剂，该佐剂可以使用常规的流感裂解疫苗（SV）作为小鼠的抗原诱导Th1细胞和抗体。我们观察到，与单独的SV相比，以1,2-二-O-十八烯基-3-三甲基铵-丙烷（DOTMA）作为脂质成分（DOTMA-LNP）的LNP在小鼠中引起了强烈的SV特异性IgG1和IgG2反应，并且在小鼠中与其他佐剂佐剂佐剂一样有效。此外，与其他佐剂相比，DOTMA-LNPs诱导了强大的IFN-γ产生Th1细胞而没有炎症反应，这赋予了小鼠强大的交叉保护。我们还证明了DOTMA-LNP作为Th1细胞诱导疫苗佐剂的高度多功能性，使用源自严重急性呼吸综合征冠状病毒2和肺炎链球菌的疫苗抗原。我们的发现表明DOTMA-LNP作为安全有效的Th1细胞诱导佐剂的潜力，并表明LNP制剂是增强其他亚单位疫苗有效性的潜在有效佐剂。
