Serological Memory and Long-term Protection to Novel H1N1 Influenza Virus After Skin Vaccination
Serological Memory and Long-term Protection to Novel H1N1 Influenza Virus After Skin Vaccination
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DOI：
10.1093/infdis/jir094
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发表时间：
2011-08-15
影响因子：
6.4
通讯作者：
Skountzou, Ioanna
中科院分区：
文献类型：
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作者：
Koutsonanos, Dimitrios G.;Martin, Maria del Pilar;Skountzou, Ioanna
背景流感疫苗开发的一个主要目标是诱导血清学记忆和细胞应答，以提供长期保护并限制感染后的病毒传播。在这里，我们研究了皮肤接种后对2009年H1N1病毒的长期免疫诱导。BALB/c小鼠通过涂敷在皮肤上的金属微针（MN）或皮下注射接受单剂量的5 μ g灭活的A/加州/04/09病毒。MN或皮下接种引起相似的血清IgG和血凝抑制滴度和100%的保护，对致命的病毒攻击后6周接种。接种后6个月，皮下接种组在用10 × LD（50）同源病毒攻击后，功能性抗体滴度下降60%，肺部炎症广泛。相反，MN组在攻击后保持高功能性抗体滴度和IFN-γ水平，抑制病毒复制，并且没有肺部炎症的迹象。MN疫苗接种可提供针对致命攻击的完全保护，而皮下疫苗接种仅产生部分保护。MN组中检测到大量的骨髓浆细胞和脾抗体分泌细胞进一步支持了这些发现。与皮下注射相比，单次皮肤接种MN诱导了有效的长期免疫力，并提高了对2009年H1N1流感病毒的保护。
Background. A major goal in influenza vaccine development is induction of serological memory and cellular responses to confer long-term protection and limit virus spread after infection. Here, we investigate induction of long-lived immunity against the 2009 H1N1 virus after skin vaccination.Methods. BALB/c mice received a single dose of 5 mu g inactivated A/California/04/09 virus via coated metal microneedles (MN) applied to skin or via subcutaneous injection.Results. MN or subcutaneous vaccination elicited similar serum IgG and hemagglutination inhibition titers and 100% protection against lethal viral challenge 6 weeks after vaccination. Six months after vaccination, the subcutaneous group exhibited a 60% decrease in functional antibody titers and extensive lung inflammation after challenge with 10 x LD(50) of homologous virus. In contrast, the MN group maintained high functional antibody titers and IFN-gamma levels, inhibition of viral replication, and no signs of lung inflammation after challenge. MN vaccination conferred complete protection against lethal challenge, whereas subcutaneous vaccination induced only partial protection. These findings were further supported by high numbers of bone marrow plasma cells and spleen antibody-secreting cells detected in the MN group.Conclusions. A single skin vaccination with MN induced potent long-lived immunity and improved protection against the 2009 H1N1 influenza virus, compared with subcutaneous injection.