A cationic liposome-DNA complexes adjuvant (JVRS-100) enhances the immunogenicity and cross-protective efficacy of pre-pandemic influenza A (H5N1) vaccine in ferrets.
A cationic liposome-DNA complexes adjuvant (JVRS-100) enhances the immunogenicity and cross-protective efficacy of pre-pandemic influenza A (H5N1) vaccine in ferrets.
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DOI：
10.1016/j.virol.2016.02.024
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发表时间：
2016-05
期刊：
影响因子：
3.7
通讯作者：
Lu X
中科院分区：
文献类型：
--
作者：
Liu F;Sun X;Fairman J;Lewis DB;Katz JM;Levine M;Tumpey TM;Lu X
甲型流感（H5 N1）病毒继续对公共卫生构成威胁。由于灭活H5 N1疫苗免疫原性差，因此需要佐剂来提高H5 N1疫苗在人体中的免疫原性。在这里，我们研究了在雪貂的进化枝2.2衍生的疫苗的免疫原性和交叉保护效力，该疫苗添加了JVRS-100，一种由阳离子脂质体-DNA复合物（CLDC）组成的佐剂。在第一次接种后，与无佐剂疫苗相比，在用佐剂疫苗免疫的雪貂中检测到显著更高水平的血凝抑制（HAI）和中和抗体滴度。第二剂含佐剂疫苗接种后，检测到抗多个H5 N1分支病毒的HAI抗体滴度≥40。针对新分离的H5 N2和H5 N8病毒的HAI抗体也被JVRS-100增强。用异源H5 N1病毒攻击雪貂。所有接受两剂佐剂疫苗的雪貂均表现出轻度疾病，显著降低了鼻洗液病毒滴度，并保护其免受致命攻击。相比之下，接受无佐剂疫苗的雪貂表现出更大的体重减轻，高病毒滴度，6只动物中有3只死于致命攻击。我们的研究结果表明，JVRS-100加入到H5 N1疫苗增强免疫原性和交叉保护对致命的H5 N1病毒疾病的雪貂。JVRS-100作为流感疫苗的潜在佐剂值得进一步研究。
Influenza A (H5N1) viruses continue to pose a public health threat. As inactivated H5N1 vaccines are poorly immunogenic, adjuvants are needed to improve the immunogenicity of H5N1 vaccine in humans. Here, we investigated the immunogenicity and cross-protective efficacy in ferrets of a clade 2.2-derived vaccine with addition of JVRS-100, an adjuvant consisting of cationic liposome–DNA complexes (CLDC). After the first vaccination, significantly higher levels of hemagglutination-inhibition (HAI) and neutralizing antibody titers were detected in ferrets immunized with adjuvanted vaccine compared to unadjuvanted vaccine. Following a second dose of adjuvanted vaccine, HAI antibody titers of ≥40 were detected against viruses from multiple H5N1 clades. HAI antibodies against newly isolated H5N2 and H5N8 viruses were also augmented by JVRS-100. Ferrets were challenged with a heterologous H5N1 virus. All ferrets that received two doses of adjuvanted vaccine exhibited mild illness, significantly reduced nasal wash virus titers and protection from lethal challenge. In contrast, ferrets that received unadjuvanted vaccine showed greater weight loss, high viral titers and 3 of 6 animals succumbed to the lethal challenge. Our results indicate that the addition of JVRS-100 to H5N1 vaccine enhanced immunogenicity and cross-protection against lethal H5N1 virus disease in ferrets. JVRS-100 warrants further investigation as a potential adjuvant for influenza vaccines.
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