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血凝素茎免疫原联合免疫可引起跨种群中和抗体及对甲流病毒的广泛保护
作者:小柯机器人 发布时间:2022/11/13 10:47:24

美国国立卫生研究院Masaru Kanekiyo团队近期取得重要工作进展,他们研究发现血凝素茎免疫原联合免疫可引起跨种群中和抗体和对甲型流感病毒的广泛保护。该研究工作2022年11月9日在线发表于《免疫》杂志上。

研究人员发现,来自第1组和第2组甲型流感病毒两种HA茎免疫原的联合免疫在小鼠、雪貂和非人灵长类动物(NHP)中,引发跨群体保护性免疫和中和抗体反应。免疫小鼠免受多种病毒的感染,所有动物模型均显示出广泛的血清中和活性。从免疫后NHP中分离出的bnAb能广泛中和并抑制多种病毒,包括H5N1和H7N9。遗传和结构分析显示猕猴和人类bnAb之间具有很强的同源性,说明了获得跨群体特异性的常见生物物理限制。疫苗诱导的茎导向跨群体保护性免疫代表着向开发广泛保护性流感疫苗迈出了一步。

据介绍,目前的流感疫苗主要诱导对高变血凝素(HA)头部的免疫,需要频繁地重新配制疫苗。相反,免疫亚显性但保守的HA茎中有一个超位点,可被广泛中和抗体(bnAb)靶向,这是通用疫苗的主要靶点。

附:英文原文

Title: Co-immunization with hemagglutinin stem immunogens elicits cross-group neutralizing antibodies and broad protection against influenza A viruses

Author: Syed M. Moin, Jeffrey C. Boyington, Seyhan Boyoglu-Barnum, Rebecca A. Gillespie, Gabriele Cerutti, Crystal Sao-Fong Cheung, Alberto Cagigi, John R. Gallagher, Joshua Brand, Madhu Prabhakaran, Yaroslav Tsybovsky, Tyler Stephens, Brian E. Fisher, Adrian Creanga, Sila Ataca, Reda Rawi, Kizzmekia S. Corbett, Michelle C. Crank, Gunilla B. Karlsson Hedestam, Jason Gorman, Adrian B. McDermott, Audray K. Harris, Tongqing Zhou, Peter D. Kwong, Lawrence Shapiro, John R. Mascola, Barney S. Graham, Masaru Kanekiyo

Issue&Volume: 2022-11-09

Abstract: Current influenza vaccines predominantly induce immunity to the hypervariable hemagglutinin(HA) head, requiring frequent vaccine reformulation. Conversely, the immunosubdominantyet conserved HA stem harbors a supersite that is targeted by broadly neutralizingantibodies (bnAbs), representing a prime target for universal vaccines. Here, we showedthat the co-immunization of two HA stem immunogens derived from group 1 and 2 influenzaA viruses elicits cross-group protective immunity and neutralizing antibody responsesin mice, ferrets, and nonhuman primates (NHPs). Immunized mice were protected frommultiple group 1 and 2 viruses, and all animal models showed broad serum-neutralizingactivity. A bnAb isolated from an immunized NHP broadly neutralized and protectedagainst diverse viruses, including H5N1 and H7N9. Genetic and structural analysesrevealed strong homology between macaque and human bnAbs, illustrating common biophysicalconstraints for acquiring cross-group specificity. Vaccine elicitation of stem-directedcross-group-protective immunity represents a step toward the development of broadlyprotective influenza vaccines.

DOI: 10.1016/j.immuni.2022.10.015

Source: https://www.cell.com/immunity/fulltext/S1074-7613(22)00556-8

期刊信息

Immunity:《免疫》,创刊于1994年。隶属于细胞出版社,最新IF:21.522
官方网址:https://www.cell.com/immunity/home
投稿链接:https://www.editorialmanager.com/immunity/default.aspx