Plant‐expressed Fc‐fusion protein tetravalent dengue vaccine with inherent adjuvant properties

• Published in: Plant biotechnology journal Vol. 16; no. 7; pp. 1283 - 1294
• Main Authors: Kim, Mi Young, Copland, Alastair, Nayak, Kaustuv, Chandele, Anmol, Ahmed, Muhammad S., Zhang, Qibo, Diogo, Gil R., Paul, Matthew J., Hofmann, Sven, Yang, Moon‐Sik, Jang, Yong‐Suk, Ma, Julian K‐C., Reljic, Rajko
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01-07-2018; John Wiley and Sons Inc
• Subjects: Adenoid; Adenoids - immunology; Adjuvants, Immunologic - genetics; Animals; Antibodies; Antibodies, Neutralizing - immunology; Antigen-presenting cells; Antigens; CD4 antigen; CD8 antigen; Cell proliferation; Children; dengue; Dengue fever; Dengue hemorrhagic fever; Dengue Vaccines - genetics; Dengue Vaccines - immunology; Epidemics; Fc receptors; Fc‐fusion proteins; Female; Fusion protein; Genetic Engineering - methods; Health aspects; human; Humans; IgG; Immune response; Immune system; Immunity; Immunity, Cellular; Immunogenicity; Immunoglobulin G; Immunoglobulin G - immunology; Interferon; Lymphocytes T; Male; Mice; Mice, Transgenic; Molecular chains; neutralizing antibodies; Nicotiana - genetics; Palatine Tonsil - immunology; Plants, Genetically Modified; Proteins; Receptors; Receptors, IgG - immunology; Receptors, Polymeric Immunoglobulin - genetics; Receptors, Polymeric Immunoglobulin - immunology; Recombinant Fusion Proteins - genetics; Recombinant Fusion Proteins - immunology; Swine; T cells; Tonsil; Transgenic mice; vaccine; Vaccines; Vector-borne diseases; Viral diseases; Viral envelope proteins; World health; IgG; neutralizing antibodies; vaccine; Fc-fusion proteins; dengue; human
• ISSN: 1467-7644; 1467-7652
• DOI: 10.1111/pbi.12869

Summary
Dengue is a major global disease requiring improved treatment and prevention strategies. The recently licensed Sanofi Pasteur Dengvaxia vaccine does not protect children under the age of nine, and additional vaccine strategies are thus needed to halt this expanding global epidemic. Here, we employed a molecular engineering approach and plant expression to produce a humanized and highly immunogenic poly‐immunoglobulin G scaffold (PIGS) fused to the consensus dengue envelope protein III domain (cEDIII). The immunogenicity of this IgG Fc receptor‐targeted vaccine candidate was demonstrated in transgenic mice expressing human FcγRI/CD64, by induction of neutralizing antibodies and evidence of cell‐mediated immunity. Furthermore, these molecules were able to prime immune cells from human adenoid/tonsillar tissue ex vivo as evidenced by antigen‐specific CD4+ and CD8+ T‐cell proliferation, IFN‐γ and antibody production. The purified polymeric fraction of dengue PIGS (D‐PIGS) induced stronger immune activation than the monomeric form, suggesting a more efficient interaction with the low‐affinity Fcγ receptors on antigen‐presenting cells. These results show that the plant‐expressed D‐PIGS have the potential for translation towards a safe and easily scalable single antigen‐based tetravalent dengue vaccine.