A comparison of non-toxin vaccine adjuvants for their ability to enhance the immunogenicity of nasally-administered anthrax recombinant protective antigen
A comparison of non-toxin vaccine adjuvants for their ability to enhance the immunogenicity of nasally-administered anthrax recombinant protective antigen
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DOI：
10.1016/j.vaccine.2013.01.012
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发表时间：
2013-03-01
期刊：
影响因子：
5.5
通讯作者：
Staats, Herman F.
中科院分区：
文献类型：
--
作者：
Gwinn, William M.;Johnson, Brandi T.;Staats, Herman F.
由于缺乏可接受的佐剂，人用鼻免疫的开发受到阻碍。虽然CT是一种有效的佐剂，但其毒性可能会阻止其在鼻疫苗中的使用。本研究比较了非毒素佐剂与CT在鼻免疫中诱导保护性抗体应答的能力。C3 H/HeN和C57 BL/6小鼠用与以下佐剂配制的rPA免疫：CT、IL-1 α、LPS、CpG、Pam 3CSK 4、3 M-019、瑞喹莫特/R848或c48/80。在疫苗接种后6小时监测血清和鼻洗液细胞因子浓度，作为先天免疫系统急性激活的生物标志物。并非所有佐剂都诱导先天性血清或鼻洗液细胞因子的显著变化，但当观察到变化时，细胞因子特征对于每种佐剂是独特的。除Pam 3CSK 4外，所有佐剂均诱导两种小鼠品系中抗rPA血清IgG滴度显著增加，而仅IL-1 α、c48/80和CpG增强粘膜抗rPA伊加。Pam 3CSK 4是唯一不能增强C3 H/HeN小鼠中血清LeTx中和抗体的诱导的佐剂，而c48/80是唯一诱导C57 BL/6小鼠中血清LeTx中和抗体增加的佐剂。在C3 H/HeN小鼠中仅CT增强血清总IgE，而在C57 BL/6小鼠中IL-1 α增强血清总IgE。佐剂影响抗原特异性血清IgG亚类和T细胞细胞因子谱，但这些反应与LeTx中和活性的诱导无关。我们的研究结果表明，诱导不同的先天性和适应性免疫反应的非毒素鼻疫苗佐剂，导致保护性体液免疫相当于CT，这些反应可能会受到宿主菌株。(c)2013爱思唯尔有限公司保留所有权利。
Development of nasal immunization for human use is hindered by the lack of acceptable adjuvants. Although CT is an effective adjuvant, its toxicity will likely prevent its use in nasal vaccines. This study compared non-toxin adjuvants to CT for their ability to induce protective antibody responses with nasal immunization. C3H/HeN and C57BL/6 mice were immunized with rPA formulated with the following adjuvants: CT, IL-1 alpha, LPS, CpG, Pam3CSK4, 3M-019, resiquimod/R848 or c48/80. Serum and nasal wash cytokine concentrations were monitored 6 h post-vaccination as biomarkers for acute activation of the innate immune system. Not all of the adjuvants induced significant changes in innate serum or nasal wash cytokines, but when changes were observed, the cytokine signatures were unique for each adjuvant. All adjuvants except Pam3CSK4 induced significantly increased anti-rPA serum IgG titers in both strains of mice, while only IL-1 alpha, c48/80 and CpG enhanced mucosal anti-rPA IgA. Pam3CSK4 was the only adjuvant unable to enhance the induction of serum LeTx-neutralizing antibodies in C3H/HeN mice while c48/80 was the only adjuvant to induce increased serum LeTx-neutralizing antibodies in C57BL/6 mice. Only CT enhanced total serum IgE in C3H/HeN mice while IL-1 alpha enhanced total serum IgE in C57BL/6 mice. The adjuvant influenced antigen-specific serum IgG subclass and T cell cytokine profiles, but these responses did not correlate with the induction of LeTx-neutralizing activity. Our results demonstrate the induction of diverse innate and adaptive immune responses by non-toxin nasal vaccine adjuvants that lead to protective humoral immunity comparable to CT and that these responses may be influenced by the host strain. (c) 2013 Elsevier Ltd. All rights reserved.