Intramuscular immunization of mice with live influenza virus is more immunogenic and offers greater protection than immunization with inactivated virus.
Intramuscular immunization of mice with live influenza virus is more immunogenic and offers greater protection than immunization with inactivated virus.
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DOI：
10.1186/1743-422x-8-251
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发表时间：
2011-05-21
期刊：
影响因子：
4.8
通讯作者：
Eichelberger MC
中科院分区：
文献类型：
--
作者：
Harris K;Ream R;Gao J;Eichelberger MC
流感病毒继续导致婴幼儿住院率居高不下。需要两剂三价灭活疫苗才能产生具有保护作用的血凝抑制（HAI）抗体。因此需要一种具有增强免疫原性的疫苗制剂。用A/Wisconsin/67/2005 （H3N2）活制剂和灭活制剂肌内接种小鼠。血清细胞因子水平、血凝素（HA）特异性抗体反应和核蛋白（NP）特异性CD8+ T细胞反应在接种疫苗组之间进行比较，并与鼻内感染后测量的反应进行比较。通过测量经鼻内感染异亚型病毒a /PR/8/34 （H1N1）的小鼠肺部病毒滴度和体重减轻，比较了每种疫苗类型的保护效果。与用灭活病毒进行IM免疫相比，肌内注射活病毒可产生更多的IFN-α、IL-12和IFN-γ、ha特异性抗体和病毒特异性CD8+ T细胞。这些增加与活病毒疫苗接种组在接受亚致死剂量异亚型病毒攻击后第7天体重减轻和肺部病毒减少相对应。炎症细胞因子、HA抗体滴度和CD8+ T细胞反应比灭活病毒传递的IM更高。这些增加的应答与对异亚型病毒攻击的更强保护相关，表明用活流感病毒肌肉免疫可能是提高疫苗免疫原性和扩大儿科人群保护的实用手段。
Influenza virus continues to cause significant hospitalization rates in infants and young children. A 2-dose regime of trivalent inactivated vaccine is required to generate protective levels of hemagglutination inhibiting (HAI) antibodies. A vaccine preparation with enhanced immunogenicity is therefore desirable. Mice were inoculated intramuscularly (IM) with live and inactivated preparations of A/Wisconsin/67/2005 (H3N2). Serum cytokine levels, hemagglutinin (HA)-specific antibody responses and nucleoprotein (NP)-specific CD8+ T cell responses were compared between vaccinated groups, as well as to responses measured after intranasal infection. The protective efficacy of each vaccine type was compared by measuring virus titers in the lungs and weight loss of mice challenged intranasally with a heterosubtypic virus, A/PR/8/34 (H1N1). Intramuscular administration of live virus resulted in greater amounts of IFN-α, IL-12 and IFN-γ, HA-specific antibodies, and virus-specific CD8+ T cells, than IM immunization with inactivated virus. These increases corresponded with the live virus vaccinated group having significantly less weight loss and less virus in the lungs on day 7 following challenge with a sublethal dose of a heterosubtypic virus. Inflammatory cytokines, antibody titers to HA and CD8+ T cell responses were greater to live than inactivated virus delivered IM. These increased responses correlated with greater protection against heterosubtypic virus challenge, suggesting that intramuscular immunization with live influenza virus may be a practical means to increase vaccine immunogenicity and to broaden protection in pediatric populations.