Plant‐based, adjuvant‐free, potent multivalent vaccines for avian influenza virus via <i>Lactococcus</i> surface display
Shi‐Jian Song, Gyeong‐Im Shin, Jin-Yong Noh, Jiho Lee, Deok‐Hwan Kim, Gyeong Ryul Ryu, Gyeongik Ahn, Hyung-Min Jeon, Hai‐Ping Diao, Youngmin Park, Min Gab Kim, Woe‐Yeon Kim, Young‐Jin Kim, Eun‐Ju Sohn, Chang‐Seon Song, Inhwan Hwang
Abstract
Abstract Influenza epidemics frequently and unpredictably break out all over the world, and seriously affect the breeding industry and human activity. Inactivated and live attenuated viruses have been used as protective vaccines but exhibit high risks for biosafety. Subunit vaccines enjoy high biosafety and specificity but have a few weak points compared to inactivated virus or live attenuated virus vaccines, especially in low immunogenicity. In this study, we developed a new subunit vaccine platform for a potent, adjuvant‐free, and multivalent vaccination. The ectodomains of hemagglutinins (HAs) of influenza viruses were expressed in plants as trimers (tHAs) to mimic their native forms. tHAs in plant extracts were directly used without purification for binding to inactivated Lactococcus (iLact) to produce iLact‐tHAs, an antigen‐carrying bacteria‐like particle (BLP). tHAs BLP showed strong immune responses in mice and chickens without adjuvants. Moreover, simultaneous injection of two different antigens by two different formulas, tHA H5N6 + H9N2 BLP or a combination of tHA H5N6 BLP and tHA H9N2 BLP, led to strong immune responses to both antigens. Based on these results, we propose combinations of plant‐based antigen production and BLP‐based delivery as a highly potent and cost‐effective platform for multivalent vaccination for subunit vaccines.