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

d live viral NT (,2-fold) assays (Table 3) , MVTT HA-QH was still able to induce significant levels of NT and HI antibody responses against the heterologous human A/ VN/1194/04 strain. Importantly, all MVTT HA-QH -vaccinations were completely protected against challenges with pathogenic A/ BhG/QH/1/05 and A/VN/1194/04, respectively ( Fig. 5 and 6 ). These findings indicated that MVTT HA-QH displayed a potential to overcome the problem of antigenic drift between clade 1 and clade 2.2, and therefore, is an attractive target vaccine for further clinical development. H5 from A/Anhui/2/05 appeared to be a weak antigen when using MVTT as a vector. This was most likely caused by mutations inducing conformational changes and hid of antigenic sites of HA (Table. 1), because the HA protein was efficiently expressed in MVTT -HA-AH infected Vero cells (Fig. 2) , and MVTT HA-AH was able to induce NT responses after the 2nd immunization against the Qinghai strain (Fig. 3C) . Consistently, A/Anhui/1/2005 is less sensitive to the neutralizing activity of MVTT -HA-QH -induced antibodies compared to other H5N1 influenza viruses, including strain A/duck/Fujian/1734/2005, which also belongs to clade 2.3.4 ( Fig. 3 and 4) . Two out of five mice in the oral administration group did not respond to the MVTT -HA-QH vaccine after two immunizations due to individual variance.