Robert Koch Institute, Nordufer 20, 13353 Berlin, Germany.
Vaccine. 2011 Feb 11;29(8):1690-9. doi: 10.1016/j.vaccine.2010.12.037. Epub 2010 Dec 30.
The recent H1N1 influenza pandemic and the inevitable delay between identification of the virus and production of the specific vaccine have highlighted the urgent need for new generation influenza vaccines that can preemptively induce broad immunity to different strains of the virus. In this study we have produced AAV-based vectors expressing the A/Mexico/4603/2009 (H1N1) hemagglutinin (HA), nucleocapsid (NP) and the matrix protein M1 and have evaluated their ability to induce specific immune response and protect mice against homologous and heterologous challenge. Each of the vaccine vectors elicited potent cellular and humoral immune responses in mice. Although immunization with AAV-M1 did not improve survival after challenge with the homologous strain, immunization with the AAV-H1 and AAV-NP vectors resulted in survival of all mice, as did inoculation with a combination of all three vectors. Furthermore, trivalent vaccination also conferred partial protection against challenge with the highly heterologous and virulent A/PR/8/34 strain of H1N1 influenza.
最近的 H1N1 流感大流行以及在鉴定病毒和生产特定疫苗之间不可避免的延迟，突显了迫切需要新一代流感疫苗，以便能够预先诱导对病毒不同毒株的广泛免疫。在这项研究中，我们生产了基于 AAV 的载体，表达 A/Mexico/4603/2009（H1N1）血凝素（HA）、核衣壳（NP）和基质蛋白 M1，并评估了它们诱导特异性免疫应答和保护小鼠免受同源和异源攻击的能力。每种疫苗载体都能在小鼠中引发强烈的细胞和体液免疫应答。尽管用 AAV-M1 免疫接种不能提高对同源株的攻击后的存活率，但用 AAV-H1 和 AAV-NP 载体进行免疫接种可使所有小鼠存活，接种三种载体的混合物也可使所有小鼠存活。此外，三价疫苗接种还可部分预防对高度异源和高毒力的 A/PR/8/34 株 H1N1 流感的攻击。
