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

In our previous study, we generated a replicating Modified Vaccinia Tian Tan (MVTT) from Vaccinia Tian Tan (VTT) by removing the hemagglutinin gene and an 11,944bp genomic region from the HindIII fragment C2L to F3L in VTT [20] . VTT has been used extensively as a smallpox vaccine for millions of people in China before the 1980's [21] and was successfully developed into a vaccine vector for rabies and hepatitis B viruses [22, 23] . Compared to VTT, MVTT is very safe, as it has been shown to not replicate in mouse brain and does not cause death after intracranial injection or body weight loss after intranasal inoculation in immuno-deficient mice [20] . Moreover, using the spike glycoprotein (S) of SARS-CoV as the test antigen, we found that MVTT is superior to MVA for inducing high levels of neutralizing antibody via mucosal vaccination [24] . In this report, using MVTT as a live vaccine vector, we constructed MVTT HA-QH and MVTT HA-AH , which expresses the H5 gene of a goosederived Qinghai strain A/Bar-headed Goose/Qinghai/1/2005 or human-derived Anhui Strain A/Anhui/1/2005. We determined the immunogenicity and efficacy of both vaccine constructs in mice against homologous and heterologous human H5N1 influenza viruses.