Cationic Lipid/DNA Complex-Adjuvanted Influenza A Virus Vaccination Induces Robust Cross-Protective Immunity
Cationic Lipid/DNA Complex-Adjuvanted Influenza A Virus Vaccination Induces Robust Cross-Protective Immunity
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DOI：
10.1128/jvi.00769-10
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发表时间：
2010-12-01
影响因子：
5.4
通讯作者：
Lewis, David B.
中科院分区：
文献类型：
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作者：
Hong, David K.;Chang, Stella;Lewis, David B.
甲型流感病毒是一种负链分段RNA病毒，其中抗原性不同的病毒亚型由血凝素（HA）和神经氨酸酶（NA）主要病毒表面蛋白定义。理想的甲型流感病毒灭活疫苗不仅能诱导高度稳定的株特异性体液和T细胞免疫应答，而且还能诱导交叉保护性免疫，其中对特定病毒亚型（例如，例如，在一个实施例中，H3 N2）将保护免受其他病毒亚型（e。例如，在一个实施例中，H1N1）。交叉保护性免疫将有助于限制新出现的抗原性新菌株的爆发。在这里，我们表明，在小鼠中加入阳离子脂质/非编码DNA复合物（CLDC）作为佐剂的全灭活甲型流感病毒疫苗诱导更强大的适应性免疫反应的数量和质量比氢氧化铝（明矾），这是目前最广泛使用的佐剂在临床人类疫苗接种。CLDC佐剂疫苗诱导更高的总流感病毒特异性IgG，特别是IgG 2a/c亚类。与明矾佐剂疫苗相比，CLDC佐剂疫苗诱导了更高水平的产生多细胞因子的流感病毒特异性CD 4和CD 8 T细胞。重要的是，含CLDC佐剂的疫苗提供了显著的交叉保护，使其免受亚致死或致死甲型流感病毒的攻击，与疫苗接种所用的不同亚型。由CLDC佐剂提供的这种上级交叉保护需要CD 8 T细胞识别由经典主要组织相容性复合体I类蛋白呈递的病毒肽。总之，这些结果表明，CLDC在疫苗策略中具有特别的前景，其中T细胞发挥重要作用，并可能为通过灭活流感病毒疫苗更有效地控制人类流感流行和大流行提供新的机会。
Influenza A virus is a negative-strand segmented RNA virus in which antigenically distinct viral subtypes are defined by the hemagglutinin (HA) and neuraminidase (NA) major viral surface proteins. An ideal inactivated vaccine for influenza A virus would induce not only highly robust strain-specific humoral and T-cell immune responses but also cross-protective immunity in which an immune response to antigens from a particular viral subtype (e. g., H3N2) would protect against other viral subtypes (e. g., H1N1). Cross-protective immunity would help limit outbreaks from newly emerging antigenically novel strains. Here, we show in mice that the addition of cationic lipid/noncoding DNA complexes (CLDC) as adjuvant to whole inactivated influenza A virus vaccine induces significantly more robust adaptive immune responses both in quantity and quality than aluminum hydroxide (alum), which is currently the most widely used adjuvant in clinical human vaccination. CLDC-adjuvanted vaccine induced higher total influenza virus-specific IgG, particularly for the IgG2a/c subclass. Higher levels of multicytokine-producing influenza virus-specific CD4 and CD8 T cells were induced by CLDC-adjuvanted vaccine than with alum-adjuvanted vaccine. Importantly, CLDC-adjuvanted vaccine provided significant cross-protection from either a sublethal or lethal influenza A viral challenge with a different subtype than that used for vaccination. This superior cross-protection afforded by the CLDC adjuvant required CD8 T-cell recognition of viral peptides presented by classical major histocompatibility complex class I proteins. Together, these results suggest that CLDC has particular promise for vaccine strategies in which T cells play an important role and may offer new opportunities for more effective control of human influenza epidemics and pandemics by inactivated influenza virus vaccine.