Poly(I:C)/alum mixed adjuvant priming enhances HBV subunit vaccine-induced immunity in mice when combined with recombinant adenoviral-based HBV vaccine boosting.
Poly(I:C)/alum mixed adjuvant priming enhances HBV subunit vaccine-induced immunity in mice when combined with recombinant adenoviral-based HBV vaccine boosting.
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DOI：
10.1371/journal.pone.0054126
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Tan W
中科院分区：
文献类型：
--
作者：
Chuai X;Chen H;Wang W;Deng Y;Wen B;Ruan L;Tan W
病毒特异性细胞免疫应答在急性或慢性HBV感染期间的病毒清除中起关键作用。目前，市售的HBV疫苗与明矾佐剂结合使用，主要刺激Th 2免疫反应。因此，迫切需要开发新的治疗性HBV疫苗佐剂和免疫策略，也促进Th 1和CTL应答。为了提高新型HBSS 1 HBV疫苗诱导的免疫力，我们评估了佐剂（包括明矾、CpG和聚核糖肌苷酸聚核糖胞苷酸[poly（I：C）]）在用重组腺病毒载体疫苗rAdSS 1加强免疫时增强应答的能力。通过酶联免疫吸附测定（ELISA）、ELISpot和细胞因子释放测定在C57 BL/6小鼠中评估对不同佐剂组合的免疫应答。在测试的组合中，具有CpG/明矾和聚（I：C）/明矾引发组合的HBV蛋白颗粒疫苗加速特异性血清转化，并产生具有Th 1偏倚的高抗体（抗PreS 1、抗S抗体）滴度。在用重组腺病毒载体疫苗rAdSS 1加强免疫后，两组都产生了强烈的多抗原（S和PreS 1）特异性细胞免疫应答。用poly（I：C）/明矾引发的HBSS 1免疫也产生了高水平的CD 4+和CD 8 + T细胞应答（就Th 1细胞因子（IFN-γ和IL-2）而言）。蛋白质疫苗HBSS 1与混合聚（I：C）/明矾佐剂引发，随后是rAdSS 1疫苗加强，最大化特异性抗体和Th 1偏向的细胞免疫应答。该方案可能在HBV治疗性疫苗的开发中被证明是有用的。此外，这种有希望的策略可能适用于其他持续感染的疫苗，如人类免疫缺陷病毒和结核病。
Virus-specific cellular immune responses play a critical role in virus clearance during acute or chronic HBV infection. Currently, the commercially available HBV vaccine is combined with alum adjuvant, which stimulates mainly Th2 immune responses. Therefore, development of new therapeutic HBV vaccine adjuvants and immune strategies that also promote Th1 and CTL responses is urgently needed. To improve the immunity induced by the novel HBSS1 HBV vaccine, we evaluated the ability of adjuvants, including alum, CpG and polyriboinosinic polyribocytidylic acid [poly(I:C)], to enhance the response when boosted with the recombinant adenoviral vector vaccine rAdSS1. The immune responses to different adjuvant combinations were assessed in C57BL/6 mice by enzyme-linked immunosorbent assay (ELISA), ELISpot and cytokine release assays. Among the combinations tested, a HBV protein particle vaccine with CpG/alum and poly(I:C)/alum priming combinations accelerated specific seroconversion and produced high antibody (anti-PreS1, anti-S antibody) titres with a Th1 bias. After boosting with recombinant adenoviral vector vaccine rAdSS1, both groups produced a strong multi-antigen (S and PreS1)-specific cellular immune response. HBSS1 immunisation with poly(I:C)/alum priming also generated high-level CD4+ and CD8+ T cell responses in terms of Th1 cytokines (IFN-γand IL-2). The protein-vaccine HBSS1 with mixed poly(I:C)/alum adjuvant priming, followed by a rAdSS1 vaccine boost, maximises specific antibody and Th1-biased cellular immune responses. This regime might prove useful in the development of HBV therapeutic vaccines. Furthermore, this promising strategy might be applied to vaccines against other persistent infections, such as human immunodeficiency virus and tuberculosis.
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