Virus-like particles displaying envelope domain III of dengue virus type 2 induce virus-specific antibody response in mice.

Currently, dengue represents one of the most significant arboviral disease worldwide, for which a vaccine is not yet available. Persistent challenges in live viral dengue vaccines have sparked a keen interest in exploring non-replicating dengue vaccines. We have examined the feasibility of using the methylotrophic yeast Pichia pastoris to develop a chimeric vaccine candidate displaying the dengue virus type-2 (DENV-2) envelope domain III (EDIII), implicated in host receptor binding and in the induction of virus-neutralizing antibodies, on the surface of non-infectious virus-like particles (VLP)-based on the Hepatitis B virus core antigen (HBcAg). We designed a fusion antigen by inserting DENV-2 EDIII into c/e1 loop of HBcAg. A codon-optimized gene encoding this fusion antigen was integrated into the genome of P. pastoris, under the control of the Alcohol Oxidase 1 promoter. The antigen was expressed by methanol induction and purified to near homogeneity by Ni(2+) affinity chromatography. The purified antigen was characterized physically and functionally to evaluate its ability to assemble into VLPs, and elicit DENV-2-specific antibodies in mice. This fusion antigen was expressed successfully to high yields and purified to near homogeneity. Electron microscopy and competitive ELISA analyses showed that it formed VLPs in which the EDIII moiety was accessible to different EDIII-specific antibodies. These VLPs were immunogenic in mice, stimulating the production of antibodies that could specifically recognize DENV-2 and neutralize its infectivity. However, virus-neutralizing antibody titers were modest. Our data show: (i) insertion of EDIII into the c/e1 loop of HBcAg does not compromise particle assembly; and (ii) the chimeric VLPs elicit a specific humoral response against DENV-2. The strategy of displaying dengue virus EDIII using a VLP platform will need further optimization before it may be developed into a viable alternative option.

Arora U ，Tyagi P ，Swaminathan S ，Khanna N ... -  《-》

Chimeric Hepatitis B core antigen virus-like particles displaying the envelope domain III of dengue virus type 2.

Arora U ，Tyagi P ，Swaminathan S ，Khanna N ... -  《JOURNAL OF NANOBIOTECHNOLOGY》

Tetravalent recombinant dengue virus-like particles as potential vaccine candidates: immunological properties.

Liu Y ，Zhou J ，Yu Z ，Fang D ，Fu C ，Zhu X ，He Z ，Yan H ，Jiang L ... -  《BMC MICROBIOLOGY》

Virus-like particles derived from Pichia pastoris-expressed dengue virus type 1 glycoprotein elicit homotypic virus-neutralizing envelope domain III-directed antibodies.

Poddar A ，Ramasamy V ，Shukla R ，Rajpoot RK ，Arora U ，Jain SK ，Swaminathan S ，Khanna N ... -  《BMC BIOTECHNOLOGY》

Tests in mice of a dengue vaccine candidate made of chimeric Junin virus-like particles and conserved dengue virus envelope sequences.

Mareze VA ，Borio CS ，Bilen MF ，Fleith R ，Mirazo S ，Mansur DS ，Arbiza J ，Lozano ME ，Bruña-Romero O ... -  《-》