Department of Virology, Statens Serum Institut, Copenhagen, Denmark.
Influenza Other Respir Viruses. 2011 Jan;5(1):13-23. doi: 10.1111/j.1750-2659.2010.00177.x. Epub 2010 Nov 3.
Alternative influenza vaccines and vaccine production forms are needed as the conventional protein vaccines do not induce broad cross-reactivity against drifted strains. Furthermore, fast vaccine production is especially important in a pandemic situation, and broader vaccine reactivity would diminish the need for frequent change in the vaccine formulations.
In this study, we compared the ability of pandemic influenza DNA vaccines to induce immunity against distantly related strains within a subtype with the immunity induced by conventional trivalent protein vaccines against homologous virus challenge.
Ferrets were immunised by particle-mediated epidermal delivery (gene gun) with DNA vaccines based on the haemagglutinin (HA) and neuraminidase (NA) and/or the matrix (M) and nucleoprotein genes of the 1918 H1N1 Spanish influenza pandemic virus or the 1968 H3N2 Hong Kong influenza pandemic virus. The animals were challenged with contemporary H1N1 or H3N2 viruses.
We demonstrated that DNA vaccines encoding proteins of the original 1918 H1N1 pandemic virus induced protective cross-reactive immune responses in ferrets against infection with a 1947 H1N1 virus and a recent 1999 H1N1 virus. Similarly, a DNA vaccine, based on the HA and NA of the 1968 H3N2 pandemic virus, induced cross-reactive immune responses against a recent 2005 H3N2 virus challenge.
DNA vaccines based on pandemic or recent seasonal influenza genes induced cross-reactive immunity against contemporary virus challenge as good as or superior to contemporary conventional trivalent protein vaccines. This suggests a unique ability of influenza DNA to induce cross-protective immunity against both contemporary and long-time drifted viruses.
由于传统的蛋白疫苗不能诱导对漂移株的广泛交叉反应,因此需要替代流感疫苗和疫苗生产形式。此外,在大流行情况下快速生产疫苗尤为重要,更广泛的疫苗反应性将减少频繁改变疫苗配方的需求。
在这项研究中,我们比较了大流行性流感 DNA 疫苗诱导对亚属内远距离相关株的免疫能力与传统三价蛋白疫苗诱导对同源病毒攻击的免疫能力。
通过粒子介导的表皮传递(基因枪)用基于血凝素(HA)和神经氨酸酶(NA)以及基质(M)和核蛋白基因的 1918 年 H1N1 西班牙流感大流行病毒或 1968 年 H3N2 香港流感大流行病毒的 DNA 疫苗对雪貂进行免疫。用当代 H1N1 或 H3N2 病毒对动物进行攻击。
我们证明了编码 1918 年 H1N1 大流行病毒原始蛋白的 DNA 疫苗在雪貂中诱导了针对 1947 年 H1N1 病毒和最近的 1999 年 H1N1 病毒感染的保护性交叉反应性免疫应答。同样,基于 1968 年 H3N2 大流行病毒的 HA 和 NA 的 DNA 疫苗诱导了针对最近的 2005 年 H3N2 病毒攻击的交叉反应性免疫应答。
基于大流行或最近季节性流感基因的 DNA 疫苗诱导的交叉反应性免疫应答与当代常规三价蛋白疫苗一样好或更好,这表明流感 DNA 具有诱导针对当代和长时间漂移病毒的交叉保护免疫的独特能力。