Science医学：通用型流感疫苗近在咫尺

科学家克服主要障碍，即将进入临床试验

　　

生物通报道：免疫系统在感染流感病毒后会产生靶标病毒表面蛋白血球凝集素HA的中和性抗体，但流感病毒HA的抗原结构变化得很快。为动物和人类接种疫苗能够诱使机体产生抗体靶标高度保守的HA茎部，从而中和多种流感病毒。这种能够诱使机体产生广谱中和性抗体的疫苗就被称为通用型流感疫苗，这种疫苗能够抵御大多数甚至所有流感病毒毒株。

然而在开发通用流感疫苗的过程中科学家面临着一个严峻的问题：接触流感病毒或接种疫苗产生的pre-existing 免疫（预存免疫）是否会阻碍广谱中和性抗体的产生？如果答案是肯定的，那么也许通用型流感疫苗就只能在接触流感病毒或者疫苗较少的儿童体内才能发挥良好作用。

日前，美国国家过敏与传染病研究所NIAID疫苗研究中心VRC的研究人员通过小鼠和雪貂实验证实，即使动物体内对流感已有预存免疫，prime-boost疫苗策略也依然可以诱使动物体内产生能够广泛中和流感病毒的抗体。文章发表在Science旗下医学刊物Science Translational Medicine杂志上。

这种疫苗策略包括初期注射DNA疫苗，随后通过接种失活的季节性流感疫苗进行加强。不论动物接触过流感病毒还是接种了标准的季节性流感疫苗，这种疫苗接种策略都可以无视预存免疫，使感染或接种过流感病毒的小鼠和雪貂体内产生广谱中和性抗体。研究显示，对流感免疫的雪貂进行prime-boost接种策略，能够使雪貂抵御不相匹配的其他流感病毒毒株。研究人员指出，如果该策略在人体中也能产生同样的效果，人们就有望开发出适用于所有年龄段人群的长效流感疫苗。

该研究证实不论是否接触过流感病毒，疫苗接种策略都可以诱导动物机体产生针对病毒HA茎部的广谱中和性抗体，为研发靶标流感病毒HA茎部的通用型流感疫苗提供了理论支持。目前疫苗研究中心的研究人员正在计划针对第一代通用型流感疫苗产生广谱中和性抗体的能力进行临床试验。

（生物通编辑：叶予）

生物通推荐原文摘要：

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.