Novel vaccination approach for dengue infection based on recombinant immune complex universal platform

Mi Young Kim, Rajko Reljic, Jacquelyn Kilbourne, Ivonne Ceballos-Olvera, Moon Sik Yang, Jorge Reyes-del Valle, Hugh Mason

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1830-1838
Number of pages9
JournalVaccine
Volume33
Issue number15
DOIs
StatePublished - Apr 8 2015

Fingerprint

antigen-antibody complex
dengue
Dengue
Antigen-Antibody Complex
Vaccination
vaccination
Infection
Dengue Vaccines
Complement C1q
Geminiviridae
Plant Proteins
Dengue Virus
vaccines
antigens
Ants
Dengue virus
Plant Extracts
Virus Diseases
Humoral Immunity
Affinity Chromatography

Keywords

  • Dengue
  • Ebola
  • Immune-complexes
  • Plants
  • Vaccine infection

ASJC Scopus subject areas

  • Immunology and Microbiology(all)
  • Infectious Diseases
  • Public Health, Environmental and Occupational Health
  • veterinary(all)
  • Molecular Medicine

Cite this

Kim, M. Y., Reljic, R., Kilbourne, J., Ceballos-Olvera, I., Yang, M. S., Reyes-del Valle, J., & Mason, H. (2015). Novel vaccination approach for dengue infection based on recombinant immune complex universal platform. Vaccine, 33(15), 1830-1838. https://doi.org/10.1016/j.vaccine.2015.02.036

Novel vaccination approach for dengue infection based on recombinant immune complex universal platform. / Kim, Mi Young; Reljic, Rajko; Kilbourne, Jacquelyn; Ceballos-Olvera, Ivonne; Yang, Moon Sik; Reyes-del Valle, Jorge; Mason, Hugh.

In: Vaccine, Vol. 33, No. 15, 08.04.2015, p. 1830-1838.

Research output: Contribution to journalArticle

Kim, MY, Reljic, R, Kilbourne, J, Ceballos-Olvera, I, Yang, MS, Reyes-del Valle, J & Mason, H 2015, 'Novel vaccination approach for dengue infection based on recombinant immune complex universal platform', Vaccine, vol. 33, no. 15, pp. 1830-1838. https://doi.org/10.1016/j.vaccine.2015.02.036
Kim MY, Reljic R, Kilbourne J, Ceballos-Olvera I, Yang MS, Reyes-del Valle J et al. Novel vaccination approach for dengue infection based on recombinant immune complex universal platform. Vaccine. 2015 Apr 8;33(15):1830-1838. https://doi.org/10.1016/j.vaccine.2015.02.036
Kim, Mi Young ; Reljic, Rajko ; Kilbourne, Jacquelyn ; Ceballos-Olvera, Ivonne ; Yang, Moon Sik ; Reyes-del Valle, Jorge ; Mason, Hugh. / Novel vaccination approach for dengue infection based on recombinant immune complex universal platform. In: Vaccine. 2015 ; Vol. 33, No. 15. pp. 1830-1838.
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