2012年8月17日 訊 /生物谷BIOON/ --在尋求開發(fā)一種廣譜性流感疫苗---它能夠誘導廣泛性的中和抗體產(chǎn)生,，能夠保護免受大多數(shù)或全部流感病毒毒株感染---過程中,，科學家們面臨著一個嚴肅的問題：預存免疫性(pre-existing immunity)是由之前感染過的流感病毒導致的嗎？或者疫苗阻止廣泛中和的抗體產(chǎn)生嗎,？如果是這樣的話,，廣譜流感疫苗可能在非常年輕的兒童體內作用最佳,，這是因為他們只是有限地接觸流感病毒或疫苗。
如今,，在利用小鼠和雪貂開展的研究中,，來自美國國家過敏癥與傳染病研究所疫苗研究中心的研究人員證實廣泛性中和的流感抗體確實能夠經(jīng)初次免疫-加強免疫疫苗(prime-boost vaccine)療法誘發(fā)而產(chǎn)生，甚至即便是這些動物對流感病毒產(chǎn)生預存免疫性,，也是如此,。
這種疫苗是由引發(fā)初次免疫的DNA疫苗和隨后一種用于加強免疫的滅活的季節(jié)性疫苗組成的。不論預存免疫性是由于宿主感染過流感病毒還是由于接種標準的季節(jié)性流感疫苗而產(chǎn)生的,，這并不重要,。因接受初次免疫-加強免疫疫苗接種而對流感病毒產(chǎn)生免疫性的雪貂免受不匹配的流感病毒毒株的攻擊。
根據(jù)研究人員的說法,，如果同樣的效應也能在人體中發(fā)現(xiàn)的話,，那么它可能給所有年齡的人們提供持續(xù)長期的流感保護。
幾項研究第一代廣譜流感疫苗產(chǎn)生廣泛性中和抗體能力的臨床試驗正在美國國家過敏癥與傳染病研究所疫苗研究中心進行或者計劃中,。(生物谷Bioon.com)
本文編譯自Study suggests potential hurdle to universal flu vaccine development may be overcome
doi: 10.1126/scitranslmed.3004273
PMC:
PMID:
Elicitation of broadly neutralizing influenza antibodies in animals with previous influenza exposure
The immune system responds to influenza infection by producing neutralizing antibodies to the viral surface protein, hemagglutinin (HA), which regularly changes its antigenic structure. Antibodies that target the highly conserved stem region of HA neutralize diverse influenza viruses and can be elicited through vaccination in animals and humans. Efforts to develop universal influenza vaccines have focused on strategies to elicit such antibodies; however, the concern has been raised that previous influenza immunity may abrogate the induction of such broadly protective antibodies. We show here that prime-boost immunization can induce broadly neutralizing antibody responses in influenza-immune mice and ferrets that were previously infected or vaccinated. HA stem–directed antibodies were elicited in mice primed with a DNA vaccine and boosted with inactivated vaccine from H1N1 A/New Caledonia/20/1999 (1999 NC) HA regardless of preexposure. Similarly, gene-based vaccination with replication-defective adenovirus 28 (rAd28) and 5 (rAd5) vectors encoding 1999 NC HA elicited stem-directed neutralizing antibodies and conferred protection against unmatched 1934 and 2007 H1N1 virus challenge in influenza-immune ferrets. Indeed, previous exposure to certain strains could enhance immunogenicity: The strongest HA stem–directed immune response was observed in ferrets previously infected with a divergent 1934 H1N1 virus. These findings suggest that broadly neutralizing antibodies against the conserved stem region of HA can be elicited through vaccination despite previous influenza exposure, which supports the feasibility of developing stem-directed universal influenza vaccines for humans.
