2012年8月14日 訊 /生物谷BIOON/ --近日，來自埃默里大學(xué)等處的研究者在研究流感疫苗時(shí)發(fā)現(xiàn)了一種新型方法可以克服流感疫苗的障礙“原始抗原痕跡（original antigenic sin,，OAS）”,，這種原始抗原痕跡可以損傷新型流感毒株的免疫效應(yīng),。相關(guān)研究成果已于近日刊登在了國際著名雜志PNAS上,。
OAS是一種免疫狀態(tài),，就是免疫系統(tǒng)同外界異物“做斗爭(zhēng)”,，并且適應(yīng)了這種情況的一種免疫狀態(tài),，當(dāng)機(jī)體遇到一種病毒后,，如果再次遇到和前一種病毒相近的病毒，機(jī)體的免疫系統(tǒng)便會(huì)通過產(chǎn)生抵御第一種病毒的抗體來對(duì)付第二種病毒,，最終導(dǎo)致免疫防御力降低,。
研究者通過進(jìn)行小鼠實(shí)驗(yàn)發(fā)現(xiàn)，OAS可以通過使用一種稱為佐劑的疫苗附加物來克服,，也可以通過在第二種病毒中重復(fù)進(jìn)行免疫法來克服,。
在最近的研究中，研究者用佐劑對(duì)H1NI病毒FM1進(jìn)行免疫,，隨后發(fā)現(xiàn)小鼠可以對(duì)活病毒產(chǎn)生較好的免疫效應(yīng),，這種佐劑是水包油乳劑型的角鯊烯油丸，角鯊烯（Squalene）是20世紀(jì)90年代在歐洲各國獲得執(zhí)照的一種疫苗添加劑,，但是在美國進(jìn)行使用,。當(dāng)用病毒毒株P(guān)R8進(jìn)行免疫反應(yīng)時(shí)，這種佐劑可以改善其免疫效應(yīng),。
佐劑可以使得免疫系統(tǒng)對(duì)初見的病毒進(jìn)行免疫應(yīng)答,，以便產(chǎn)生很多抗體產(chǎn)生細(xì)胞來對(duì)病毒的再次攻擊產(chǎn)生反應(yīng)。研究者的研究發(fā)現(xiàn)揭示了我們可以首次在流感疫苗中通過添加佐劑,，來克服人類的天然免疫,，尤其是兒童免疫系統(tǒng)中OAS的潛在發(fā)生。另外,，在以前感染流感病毒的老年人中OAS也可以通過佐劑使其效應(yīng)減小到最小化,。（生物谷Bioon.com）
編譯自：Flu vaccine research: overcoming 'original sin'
doi:10.1073/pnas.0912458109
PMC:
PMID:
Strategies to alleviate original antigenic sin responses to influenza viruses
Jin Hyang Kima,1, William G. Davisb, Suryaprakash Sambharab, and Joshy Jacoba,2
Original antigenic sin is a phenomenon wherein sequential exposure to closely related influenza virus variants reduces antibody (Ab) response to novel antigenic determinants in the second strain and, consequently, impairs the development of immune memory. This could pose a risk to the development of immune memory in persons previously infected with or vaccinated against influenza. Here, we explored strategies to overcome original antigenic sin responses in mice sequentially exposed to two closely related hemagglutinin 1 neuraminidase 1 (H1N1) influenza strains A/PR/8/34 and A/FM/1/47. We found that dendritic cell–activating adjuvants [Bordetella pertussis toxin (PT) or CpG ODN or a squalene-based oil-in-water nanoemulsion (NE)], upon administration during the second viral exposure, completely protected mice from a lethal challenge and enhanced neutralizing-Ab titers against the second virus. Interestingly, PT and NE adjuvants when administered during the first immunization even prevented original antigenic sin in subsequent immunization without any adjuvants. As an alternative to using adjuvants, we also found that repeated immunization with the second viral strain relieved the effects of original antigenic sin. Taken together, our studies provide at least three ways of overcoming original antigenic sin.
