Intranasal Vaccination with Murabutide Enhances Humoral and Mucosal Immune Responses to a Virus-Like Particle Vaccine
Intranasal Vaccination with Murabutide Enhances Humoral and Mucosal Immune Responses to a Virus-Like Particle Vaccine
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DOI：
10.1371/journal.pone.0041529
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发表时间：
2012-07-25
期刊：
影响因子：
3.7
通讯作者：
Herbst-Kralovetz, Melissa M.
中科院分区：
文献类型：
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作者：
Jackson, Erin M.;Herbst-Kralovetz, Melissa M.
Murabutide （MB）是一种合成免疫调节剂，可被哺乳动物细胞上的核苷酸结合寡聚结构域蛋白2 （NOD2）受体识别。MB先前已被批准在多个人体临床试验中进行测试，以确定其作为抗病毒治疗药物和注射疫苗佐剂的价值。我们发现了这种免疫调节剂的新用途；它作为粘膜佐剂，增强鼻内给药的病毒样颗粒（VLP）的免疫原性。在鼻内（IN）接种后，MB增强了诺瓦克病毒（NV） vlp特异性IgG和远端粘膜部位IgA的产生。根据血清中vlp特异性IgG、IgG1、IgG2a和IgA的分泌量以及远端粘膜部位vlp特异性IgA的分泌量，一项剂量递增研究确定100 μ g为小鼠的最佳MB剂量。用含有MB的VLP进行IN疫苗接种，与含有霍乱毒素（CT）或加地喹莫特（GARD）的VLP和含明矾的静脉注射VLP进行比较；MB组在诱导粘膜免疫反应和刺激等效的全身vlp特异性抗体方面与CT和GARD组相当，优于明矾组。这些数据支持进一步测试MB作为一种有效的粘膜佐剂，可诱导对非复制亚单位疫苗产生稳健和持久的抗体反应。
Murabutide (MB) is a synthetic immunomodulator recognized by the nucleotide-binding oligomerization domain-containing protein 2 (NOD2) receptor on mammalian cells. MB has previously been approved for testing in multiple human clinical trials to determine its value as an antiviral therapeutic, and as an adjuvant for injected vaccines. We have found a new use for this immunomodulator; it functions as a mucosal adjuvant that enhances immunogenicity of virus-like particles (VLP) administered intranasally. MB enhanced Norwalk virus (NV) VLP-specific IgG systemically and IgA production at distal mucosal sites following intranasal (IN) vaccination. A dose escalation study identified 100 mu g as the optimal MB dosage in mice, based on the magnitude of VLP-specific IgG, IgG1, IgG2a and IgA production in serum and VLP-specific IgA production at distal mucosal sites. IN vaccination using VLP with MB was compared to IN delivery VLP with cholera toxin (CT) or gardiquimod (GARD) and to parenteral VLP delivery with alum; the MB groups were equivalent to CT and GARD and superior to alum in inducing mucosal immune responses and stimulated equivalent systemic VLP-specific antibodies. These data support the further testing of MB as a potent mucosal adjuvant for inducing robust and durable antibody responses to non-replicating subunit vaccines.