1月28日,，國際學(xué)術(shù)雜志PLoS ONE在線發(fā)表了上海巴斯德研究所關(guān)于異源免疫策略DNA-VLP在抗高致病性禽流感H5N1病毒感染中的保護(hù)性作用的研究論文。這項(xiàng)研究成果由周保羅研究員領(lǐng)導(dǎo)的課題組完成。
疫苗接種是預(yù)防高致病性流感病毒H5N1大流行的有效途徑,，但是傳統(tǒng)的基于雞胚制備流感疫苗的方法在用來制備抗H5N1的疫苗時(shí)卻受到嚴(yán)重限制,，這主要是由于H5N1病毒可以殺死雞胚,。有許多新的疫苗制備形式在研究中被嘗試于應(yīng)對高致病性禽流感H5N1病毒,，例如DNA和病毒樣顆粒(VLP)類疫苗。
在本研究中,，研究人員首次將DNA和病毒樣顆粒(VLP)結(jié)合起來以一種異源初免-加強(qiáng)免疫的接種策略來應(yīng)對H5N1病毒,，并對該免疫策略和另外兩種同源免疫策略在小鼠體內(nèi)誘導(dǎo)出的中和抗體反應(yīng)和免疫保護(hù)效果進(jìn)行了比較研究。以假病毒為基礎(chǔ)的中和抗體檢測實(shí)驗(yàn)證實(shí)DNA-VLP在三種初免-加強(qiáng)免疫接種策略中所誘導(dǎo)出的中和抗體活性最高,；而DNA-DNA所誘導(dǎo)出的中和抗體活性要高于VLP-VLP的,。研究結(jié)果還表明，只有DNA-VLP和DNA-DNA, 而不是 VLP-VLP,，能在1,000 MLD50高劑量的同源H5N1病毒攻毒實(shí)驗(yàn)中保護(hù)小鼠免于死亡,。最后，也只有DNA-VLP能在1,000 MLD50的異源H5N1病毒攻毒實(shí)驗(yàn)中保護(hù)一半的小鼠免于死亡,。這些結(jié)果表明在針對高致病性禽流感H5N1病毒時(shí)，異源DNA-VLP初免-加強(qiáng)免疫接種策略能誘導(dǎo)出更強(qiáng)的中和抗體反應(yīng)和免疫保護(hù),。在未來可能的H5N1流行中,，這將為臨床上對異源DNA-VLP初免-加強(qiáng)免疫接種策略對公眾健康所起的干涉保護(hù)作用進(jìn)行評估提供理論支持。
該研究得到了法國衛(wèi)生部研究項(xiàng)目,、國家自然科學(xué)基金委,、國家科學(xué)和技術(shù)重大專項(xiàng)及李嘉誠基金會(huì)等項(xiàng)目資助。 （生物谷Bioon.com）
生物谷推薦原文出處：
PLoS One. 2011 Jan 28;6(1):e16563.
Superior Neutralizing Antibody Response and Protection in Mice Vaccinated with Heterologous DNA Prime and Virus Like Particle Boost against HPAI H5N1 Virus.
Ding H, Tsai C, Gutiérrez RA, Zhou F, Buchy P, Deubel V, Zhou P.
Abstract
BACKGROUND: Although DNA plasmid and virus-like particle (VLP) vaccines have been individually tested against highly pathogenic avian influenza (HPAI) H5N1 viruses, the combination of both vaccines into a heterologous prime-boost strategy against HPAI H5N1 viruses has not been reported before.
METHODOLOGY/PRINCIPAL FINDINGS: We constructed DNA plasmid encoding H5HA (A/Shenzhen/406H/06, subclade 2.3.4) and generated VLP expressing the same H5HA and N1NA. We then compared neutralizing antibody responses and immune protection elicited with heterologous DNA-VLP, homologous DNA-DNA and VLP-VLP prime-boost strategies against HPAI H5N1 viruses in mice. We demonstrate that DNA-VLP elicits the highest neutralizing antibody titers among the three prime-boost strategies, whereas DNA-DNA elicits higher neutralizing antibody titers than VLP-VLP. We show that although all three prime-boost strategies protect mice from death caused by 10 MLD(50) of homologous and heterologous H5N1 challenge, only DNA-VLP and DNA-DNA protect mice from infection as manifested by no weight loss and no lung pathology. In addition, we show that although DNA-VLP and DNA-DNA protect mice from death caused by 1,000 MLD(50) of homologous H5N1 challenge, only DNA-VLP protects mice from infection. Moreover, we show that after 1,000 MLD(50) of heterologous H5N1 challenge, while all mice in PBS, VLP-VLP and DNA-DNA died, 3 of 6 mice in DNA-VLP actually survived. Finally, we show that DNA-VLP completely protects mice from infection after 1,000 MLD(50) of homologous H5N1 challenge even when the challenge was administrated at 60 days post the boost.
CONCLUSIONS/SIGNIFICANCE: These results provide strong support for clinical evaluation of heterologous DNA-VLP prime-boost strategy as a public health intervention against a possible H5N1 pandemic.
