11月3日，國際期刊《Scientific Reports》在線發表了一篇題為《Natural and directed antigenic drift of the H1 infuenza virus hemagglutinin stalk domain》的研究，發現H1流感病毒HA蛋白莖域部分存在抗原漂移現象，為設計針對這一區域的通用疫苗策略提供參考。
流感病毒感染可引起季節性流行病或偶爾的大流行。2009年，一種由豬流感病毒引起的甲型H1N1流感病毒(pH1N1)在墨西哥爆發，並迅速傳播到世界各地。儘管有疫苗的保護,世衛組織估計，流感病毒已導致10億人感染，3 - 500萬例嚴重疾病，每年可導致300000 -300000人死亡。甲型流感病毒根據其表面主要的兩種糖蛋白血凝素(HA)和神經氨酸苷酶(NA)，進一步區分亞型。
HA蛋白是由HA1和HA2亞單位組成的三聚體。HA前體是未成熟的多肽鏈(HA0)，被宿主蛋白酶激活後，產生兩個亞單位HA1和HA2。HA1形成包含受體結合位點(RBS)的球狀頭部區域，與細胞表面唾液酸受體結合介導粘附，是流感病毒最不保守的部分。HA2與HA1部分殘基形成一個莖域，其中包括跨膜區域，相對保守。主要介導病毒與細胞膜的融合。季節性的流感疫苗設計策略主要是誘導針對HA球狀頭部區域的特異抗體，從而抑制HA附著在細胞表面唾液酸受體上。
由於頭部區域易發生變異，研究者們希望可通過相對保守的莖域設計出流感病毒通用型疫苗。然而，目前對莖域在自然或誘導情況下抗原變異性研究較少。本研究分析了人類H1HA頭部和莖域序列，發現兩者都有相當大的變異，只是頭部區域變異性最高。此外，研究者又從體外和體內分別證明了莖域存在抗原變異。體外實驗中，利用人類免疫血清和和針對莖域的單抗作為選擇壓力，病毒在體外培養後兩個區域內都有突變，並且此突變有利於免疫逃避。體內實驗證明莖域突變病毒在體內仍保留致病性。這些結果顯示在免疫壓力下，HA蛋白莖域可以承受有限的抗體漂移並能在體內保持適應性及毒力。這在為設計針對這一區域疫苗有重要參考意義。
Natural and directed antigenic drift of the H1 infuenza virus hemagglutinin stalk domain
Abstract
The induction of antibodies specific for the influenza HA protein stalk domain is being pursued as a universal strategy against influenza virus infections. However, little work has been done looking at natural or induced antigenic variability in this domain and the effects on viral fitness. We analyzed human H1 HA head and stalk domain sequences and found substantial variability in both, although variability was highest in the head region. Furthermore, using human immune sera from pandemic A/California/04/2009 immune subjects and mAbs specific for the stalk domain, viruses were selected in vitro containing mutations in both domains that partially contributed to immune evasion. Recombinant viruses encoding amino acid changes in the HA stalk domain replicated well in vitro, and viruses incorporating two of the stalk mutations retained pathogenicity in vivo. These findings demonstrate that the HA protein stalk domain can undergo limited drift under immune pressure and the viruses can retain fitness and virulence in vivo, findings which are important to consider in the context of vaccination targeting this domain.