Metwally Ashraf, Yousif Ausama
Veterinary Virologist and Consultant, Cairo 11441, Egypt.
Virology Department, Faculty of Veterinary Medicine, Cairo University, Giza 12211, Egypt.
Int J Mol Sci. 2017 Apr 4;18(4):766. doi: 10.3390/ijms18040766.
Successful immunization against avian influenza virus (AIV) requires eliciting an adequate polyclonal response to AIV hemagglutinin (HA) subunit 1 (HA1) epitopes. Outbreaks of highly-pathogenic (HP) AIV subtype H5N1 can occur in vaccinated flocks in many endemic areas. Protection against emerging AIV is partly hindered by the limitations of vaccine production and transport, the use of leaky vaccines, and the use of multiple, and often antigenically-diverse, vaccines. It was hypothesized that the majority of alternative functional configurations (AFC) within the AIV HA1 can be represented by the pool of vaccine seed viruses currently in production because only a finite number of AFC are possible within each substructure of the molecule. Therefore, combinations of commercial vaccines containing complementing structural units (CSU) to each HA1 substructure can elicit responses to the totality of a given emerging AIV HA1 substructure isoforms. Analysis of homology-based 3D models of vaccine seed and emerging viruses facilitated the definition of HA1 AFC isoforms. CSU-based plots were used to predict which commercial vaccine combinations could have been used to cover nine selected AFC isoforms on recent Egyptian HP AIV H5N1 outbreak viruses. It is projected that expansion of the vaccine HA1 3D model database will improve international emergency responses to AIV.
成功免疫禽流感病毒（AIV）需要对AIV血凝素（HA）亚基1（HA1）表位引发足够的多克隆反应。在许多疫区，接种疫苗的禽群中可能会爆发高致病性（HP）AIV H5N1亚型。疫苗生产和运输的局限性、使用效力不足的疫苗以及使用多种且通常抗原性不同的疫苗，在一定程度上阻碍了对新出现的AIV的防护。据推测，AIV HA1内的大多数替代功能构型（AFC）可由目前正在生产的疫苗种子病毒库来代表，因为在该分子的每个亚结构内，可能的AFC数量有限。因此，含有针对每个HA1亚结构的互补结构单元（CSU）的商业疫苗组合，可引发针对给定新出现的AIV HA1亚结构亚型整体的反应。对疫苗种子和新出现病毒的基于同源性的三维模型分析，有助于定义HA1 AFC亚型。基于CSU的图表用于预测哪些商业疫苗组合可用于覆盖近期埃及HP AIV H5N1疫情病毒上的九种选定AFC亚型。预计疫苗HA1三维模型数据库的扩展将改善对AIV的国际应急反应。
