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

Broad cross-protection is a highly desirable feature of an H5N1 vaccine to avoid the possible pandemic of H5N1 influenza viruses. However, the efficacies of currently licensed vaccines appear to be insufficient partially due to the antigenic diversity present in the virus, restricting the utility of the vaccine to a small number of specific strains. Whilst the identity of any specific pandemic strain is rather difficult to predict before the event, it would take 4-6 months or more to deliver a vaccine using current manufacturing technologies [11, 12] . Therefore, great efforts have been made toward developing vaccines with broad cross-protection against H5N1 influenza viruses, as well as improving vaccine production methods to shorten the lead-time to vaccine delivery. New approaches, such as virus-like particles (VLPs), naked DNA and adenoviral and vaccinia vector-based vaccines have been developed to prevent H5N1 viral infections [10, 13, 14] . It was reported that inactivated H5N1 influenza viruses of clades 1 and 2.1 and virus-like particles (VLPs) containing the HA, NA and M1 proteins of IN5/05 and VN/1203 showed significant cross-protective potential [15] [16] [17] . Non-replicating vaccinia vectors, such as the Modified Vaccinia Virus Ankara (MVA) carrying an HA derived from the VN/1203 strain, displayed a high level of crossprotection [18] . A veterinary vaccine expressing the H5 gene of the A/Bar-headed Goose/Qinghai/1/2005 (A/BhG/QH/1/05) also provided protection against lethal challenges of homologous and heterologous avian H5N1 influenza viruses [19] .