A Single Immunization with CoVaccine HT-Adjuvanted H5N1 Influenza Virus Vaccine Induces Protective Cellular and Humoral Immune Responses in Ferrets

A Single Immunization with CoVaccine HT-Adjuvanted H5N1 Influenza Virus Vaccine Induces Protective Cellular and Humoral Immune Responses in Ferrets
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DOI:
10.1128/jvi.00549-10
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发表时间:
2010-08-15
影响因子:
5.4
通讯作者:
Rimmelzwaan, G. F.
Rimmelzwaan, G. F.
中科院分区:
医学2区
文献类型:
--
作者:
Bodewes, R.;Kreijtz, J. H. C. M.;Rimmelzwaan, G. F.

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H5 N1亚型的高致病性禽流感A病毒继续在家禽中传播,经常报告人畜共患传播。由于仍然担心由这些高致病性病毒引起的大流行,因此人们对开发可以保护人类免受感染的流感A/H5 N1病毒疫苗感兴趣,优选在用低剂量抗原进行单次接种后。在这里,我们描述了诱导的体液和细胞免疫反应的雪貂接种后,细胞培养衍生的全灭活甲型流感病毒疫苗与新型佐剂CoVaccine HT的组合。在甲型流感病毒疫苗中添加CoVaccine HT可增加对同源和异源甲型流感/H5 N1病毒的抗体应答,并增加病毒特异性细胞介导的免疫应答。用相当于3.8 μ g血凝素(HA)的全病毒和CoVaccine HT接种一次的雪貂可保护其免受流感病毒A/VN/1194/04的同源攻击感染。此外,用相同的疫苗/佐剂组合接种一次的雪貂被部分保护免于感染来自H5 N1流感病毒的进化枝2.1的异源病毒。因此,使用新型佐剂CoVaccine HT与细胞培养衍生的灭活甲型流感/H5 N1病毒抗原是一种有前途且节省剂量的疫苗方法,值得进一步临床评估。
Highly pathogenic avian influenza A viruses of the H5N1 subtype continue to circulate in poultry, and zoonotic transmissions are reported frequently. Since a pandemic caused by these highly pathogenic viruses is still feared, there is interest in the development of influenza A/H5N1 virus vaccines that can protect humans against infection, preferably after a single vaccination with a low dose of antigen. Here we describe the induction of humoral and cellular immune responses in ferrets after vaccination with a cell culture-derived whole inactivated influenza A virus vaccine in combination with the novel adjuvant CoVaccine HT. The addition of CoVaccine HT to the influenza A virus vaccine increased antibody responses to homologous and heterologous influenza A/H5N1 viruses and increased virus-specific cell-mediated immune responses. Ferrets vaccinated once with a whole-virus equivalent of 3.8 mu g hemagglutinin (HA) and CoVaccine HT were protected against homologous challenge infection with influenza virus A/VN/1194/04. Furthermore, ferrets vaccinated once with the same vaccine/adjuvant combination were partially protected against infection with a heterologous virus derived from clade 2.1 of H5N1 influenza viruses. Thus, the use of the novel adjuvant CoVaccine HT with cell culture-derived inactivated influenza A/H5N1 virus antigen is a promising and dose-sparing vaccine approach warranting further clinical evaluation.