Novel vaccination approach for dengue infection based on recombinant immune complex universal platform.
Dengue infection is on the rise in many endemic areas of the tropics. Vaccination remains the most realistic strategy for prevention of this potentially fatal viral disease but there is currently no effective vaccine that could protect against all four known serotypes of the dengue virus. This study describes the generation and testing of a novel vaccination approach against dengue based on recombinant immune complexes (RIC). We modelled the dengue RIC on the existing Ebola RIC (Phoolcharoen, et al. Proc Natl Acad Sci USA 2011;108(Dec (51)):20695) but with a key modification that allowed formation of a universal RIC platform that can be easily adapted for use for other pathogens. This was achieved by retaining only the binding epitope of the 6D8 ant-Ebola mAb, which was then fused to the consensus dengue E3 domain (cEDIII), resulting in a hybrid dengue-Ebola RIC (DERIC). We expressed human and mouse versions of these molecules in tobacco plants using a geminivirus-based expression system. Following purification from the plant extracts by protein G affinity chromatography, DERIC bound to C1q component of complement, thus confirming functionality. Importantly, following immunization of mice, DERIC induced a potent, virus-neutralizing anti-cEDIII humoral immune response without exogenous adjuvants. We conclude that these self-adjuvanting immunogens have the potential to be developed as a novel vaccine candidate for dengue infection, and provide the basis for a universal RIC platform for use with other antigens.
Center of Infectious Diseases and Vaccinology, Biodesign Institute, Tempe, AZ 85287, USA; Institute for Infection and Immunity, St George's University of London, London, UK.
Mi-Young
MY
Kim
Institute for Infection and Immunity, St George's University of London, London, UK.
Rajko
R
Reljic
Center of Infectious Diseases and Vaccinology, Biodesign Institute, Tempe, AZ 85287, USA.
Jacquelyn
J
Kilbourne
School of Life Sciences, Arizona State University, Tempe, AZ 85287, USA.
Ivonne
I
Ceballos-Olvera
Department of Molecular Biology, Chonbuk National University, Jeonju-si, South Korea.
Moon-Sik
MS
Yang
School of Life Sciences, Arizona State University, Tempe, AZ 85287, USA.
Jorge
J
Reyes-del Valle
Center of Infectious Diseases and Vaccinology, Biodesign Institute, Tempe, AZ 85287, USA; School of Life Sciences, Arizona State University, Tempe, AZ 85287, USA. Electronic address: hugh.mason@asu.edu.
Hugh S
HS
Mason
D000276:Adjuvants, Immunologic; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D057134:Antibodies, Neutralizing / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology*; D000936:Antigen-Antibody Complex / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D002460:Cell Line; D015922:Complement C1q / Q000276:immunology; D003715:Dengue / Q000517:prevention & control*; D053059:Dengue Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D003716:Dengue Virus / Q000276:immunology*; D029043:Ebolavirus / Q000235:genetics / Q000276:immunology; D000939:Epitopes / Q000276:immunology; D017791:Geminiviridae / Q000235:genetics; D006801:Humans; D056724:Immunity, Humoral; D051379:Mice; D018515:Plant Leaves; D014026:Nicotiana; D014611:Vaccination / Q000379:methods*; D014759:Viral Envelope Proteins / Q000276:immunology
D000276:Adjuvants, Immunologic; D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D000936:Antigen-Antibody Complex; D053059:Dengue Vaccines; D000939:Epitopes; D014759:Viral Envelope Proteins; D015922:Complement C1q
Dengue; Ebola; Immune-complexes; Plants; Vaccine infection