J Integr Plant Biol. ›› 2021, Vol. 63 ›› Issue (8): 1505-1520.DOI: 10.1111/jipb.13141

Special Issue: Biotechnology

• Metabolism and Biochemistry • Previous Articles     Next Articles

Plant-based, adjuvant-free, potent multivalent vaccines for avian influenza virus via Lactococcus surface display

Shi‐Jian Song1, Gyeong‐Im Shin2, Jinyong Noh3, Jiho Lee4, Deok‐Hwan Kim4, Gyeongryul Ryu2, Gyeongik Ahn5, Hyungmin Jeon1, Hai‐Ping Diao1, Youngmin Park1,6, Min Gab Kim2, Woe‐Yeon Kim5, Young‐Jin Kim1, Eun‐Ju Sohn6, Chang Seon Song3,4 and Inhwan Hwang1*   

  1. 1 Department of Life Science, Pohang University of Science and Technology, Pohang 37673, Korea
    2 College of Pharmacy and Research Institute of Pharmaceutical Science, Gyeongsang National University, Jinju 660‐701, Korea
    3 KCAV Inc., Gwangjin‐gu 05029, Korea
    4 Avian Disease Laboratory, College of Veterinary Medicine, Konkuk University, Seoul 05029, Korea
    5 Division of Applied Life Science (BK21 PLUS), Institute of Agriculture & Life Sciences, Gyeongsang National University, Jinju 52828, Korea
    6 Bioapp, Inc., Pohang Technopark Complex, Pohang 37668, Korea

    *Correspondence: Inhwan Hwang (ihhwang@postech.ac.kr)
  • Received:2021-01-26 Accepted:2021-05-26 Online:2021-05-29 Published:2021-08-01

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, tHAH5N6 + H9N2 BLP or a combination of tHAH5N6 BLP and tHAH9N2 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.

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