Hemagglutinin virus-like particles incorporated with membrane-bound cytokine adjuvants provide protection against homologous and heterologous influenza virus challenge in aged mice.
Hemagglutinin virus-like particles incorporated with membrane-bound cytokine adjuvants provide protection against homologous and heterologous influenza virus challenge in aged mice.
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DOI：
10.1186/s12979-023-00344-w
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发表时间：
2023-05-11
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影响因子：
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中科院分区：
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目前的流感疫苗对年轻人的效果令人满意，但对老年人的效果较差。由于免疫衰老在数量和质量上损害了老年人的免疫反应，为不断增加的老龄化人口开发疫苗一直是一项艰巨的挑战。为了潜在地提高疫苗在老年人中的效力，我们研究了流感血凝素病毒样颗粒（HA-VLP）与糖基磷脂酰肌醇（GPI）锚定的细胞因子佐剂（GPI- gm - csf和GPI- il -12）通过蛋白质转移在老年小鼠中的免疫原性和交叉保护。与单独接种HA-VLP相比，接种含有细胞因子的VLPs （HA-VLP- cyt）后，老年小鼠肺部病毒对同源和异源流感病毒的复制明显减少。与HA-VLP单独免疫相比，HA-VLP- cyt免疫老年小鼠的IFN-γ+CD4+和IFN-γ+CD8+ T细胞反应也增强。细胞因子佐剂HA-VLP流感疫苗诱导老年小鼠对同源甲型流感病毒感染的增强保护反应。含有gpi细胞因子的HA-VLP流感疫苗也能诱导增强的T细胞反应，在缺乏中和抗体的情况下，对异源感染有更好的保护。结果表明，使用细胞因子佐剂流感HA-VLPs的疫苗接种策略可用于增强老年人对甲型流感病毒的保护。
Current influenza vaccines deliver satisfactory results in young people but are less effective in the elderly. Development of vaccines for an ever-increasing aging population has been an arduous challenge due to immunosenescence that impairs the immune response in the aged, both quantitatively and qualitatively. To potentially enhance vaccine efficacy in the elderly, we investigated the immunogenicity and cross-protection of influenza hemagglutinin virus-like particles (HA-VLP) incorporated with glycosylphosphatidylinositol (GPI)-anchored cytokine-adjuvants (GPI-GM-CSF and GPI-IL-12) via protein transfer in aged mice. Lung viral replication against homologous and heterologous influenza viruses was significantly reduced in aged mice after vaccination with cytokine incorporated VLPs (HA-VLP-Cyt) in comparison to HA-VLP alone. Enhanced IFN-γ+CD4+ and IFN-γ+CD8+ T cell responses were also observed in aged mice immunized with HA-VLP-Cyt when compared to HA-VLP alone. Cytokine-adjuvanted influenza HA-VLP vaccine induced enhanced protective response against homologous influenza A virus infection in aged mice. Influenza HA-VLP vaccine with GPI-cytokines also induced enhanced T cell responses correlating with better protection against heterologous infection in the absence of neutralizing antibodies. The results suggest that a vaccination strategy using cytokine-adjuvanted influenza HA-VLPs could be used to enhance protection against influenza A virus in the elderly.
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DOI：
10.4049/jimmunol.1200061
发表时间：
2013-01-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
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作者：
Green AM;Difazio R;Flynn JL
通讯作者：
Flynn JL
影响因子：
5.5
作者：
Huleatt, James W.;Jacobs, Andrea R.;Powell, T. J.
通讯作者：
Powell, T. J.
影响因子：
6.2
作者：
Kang SM;Kim MC;Compans RW
通讯作者：
Compans RW
影响因子：
1.5
作者：
Car, BD;Eng, VM;Anderson, TD
通讯作者：
Anderson, TD
影响因子：
5.5
作者：
DiazGranados, Carlos A.;Dunning, Andrew J.;Talbot, H. Keipp
通讯作者：
Talbot, H. Keipp