A Replicating Modified Vaccinia Tiantan Strain Expressing an Avian-Derived Influenza H5N1 Hemagglutinin Induce Broadly Neutralizing Antibodies and Cross-Clade Protective Immunity in Mice

Xiao, Haixia; Liu, Li; Zhu, Qingyu; Tan, Zhiwu; Yu, Wenbo; Tang, Xian; Zhan, Dawei; Du, Yanhua; Wang, Haibo; Liu, Di; Li, Zhixin; Yuen, Kwok-Yung; Ho, David D.; Gao, George F.; Chen, Zhiwei

The HA gene of A/BhG/QH/1/05 and A/Anhui/1/2005 were chosen for vaccine construction because A/BhG/QH/1/05 represents the prototype of clade 2.2 highly pathogenic influenza A H5N1 viruses, which has led to sporadic human infections around the world (Fig. 1) , whilst A/Anhui/1/2005 is a WHO recommended vaccine strain isolated from a human patient, which may induce a better immune response against human isolates. We analyzed the sequences of the HA genes derived from the human A/Xingjiang/1/06 strain and those from other countries. When compared with the HA of A/BhG/QH/1/05, the major antigenic sites within clade 2.2 were relatively conserved despite viral evolution occurring over two to three years outside the Qinghai Lake area (Table 1) . A/Anhui/1/2005 belongs to clade 2.3.4, in which the major antigenic sites are very different from clade 2.2, but rather conserved within clade 2.3.4. We hypothesized that vaccines based on the HA would at least offer protection to human H5N1 influenza viruses of the same clade.