Dengue Vaccine Candidate Development
Dengue virus infection is a major public health problem worldwide especially in tropical and subtropical regions. More than 400 million individuals are infected annually. Vaccine is considered as an effective strategy to reduce disease burden as well as viral spreading. Although the first licensed dengue vaccine was launched, the balance of protective rate among four serotypes still needs to be explored.
DNA vaccine is an interesting vaccine platform for dengue according to its advantages. For examples, it is non-infectious, not being interfered when combined as a multivalent cocktail, easy to construct and modify, and rapidly produced and thermo-stable. Currently, various DNA vaccines have been evaluated in clinical trials both for infectious and non-infectious diseases. Theoretically, the immunogenicity that induced by DNA vaccine is relatively low when compared with live-vaccine platforms. However, the immunogenicity was significantly increased when DNA was delivered by high pressure needle-free injection and electroporation which is correlated with plasmid uptake and target protein expression. A combination of DNA with nanoparticle carrier or adjuvants, was also used to enhance DNA vaccine immunogenicity.
Tetravalent Dengue DNA Vaccine
We are currently developing tetravalent dengue DNA vaccine. The vaccine construct was designed as a consensus sequence to encode proteins (pre-membrane and envelope) for each dengue serotype. The vaccine has been tested for its immunogenicity both in monovalent or combined as tetravalent by using in vivo electroporation. The vaccine showed promising results in mice then further evaluated in non-human primates. Moreover, in collaboration with Professor Nopporn Sittisombut, Faculty of Medicine, Chiang Mai University, live-attenuated virus/DNA heterologous prime/boost regimen were tested in non-human primates to evaluate the immunogenicity and protective efficacy after virus challenge. The preliminary results showed encouraging results with 100% protection after DENV-2 challenge.
PLoS One. 2014; 9(6): e92643
Protein expression of tetravalent dengue DNA vaccine constructs
PLoS One. 2014; 9(6): e92643
Neutralizing antibody responses in mice following the tetravalent dengue DNA vaccine immunization
Currently, we are also exploring the effective delivery system as well as adjuvant to maximize vaccine immunogenicity. We collaborated with world-class experts in liposome and adjuvant from MHRP, WRAIR, USA and University of Lausanne to improve vaccine immunogenicity.
Strategies to improve the immunogenicity of prM+E dengue virus type-2 DNA vaccine. Asian Pac J Allergy Immunol. 2017; 35(1): 11-19.
The immunogenicity of tetravalent dengue DNA vaccine in mice pre-exposed to Japanese encephalitis or Dengue virus antigens.Asian Pac J Allergy Immunol. 2015; 33: 182-188.
Induction of neutralizing antibody response against four dengue viruses in mice by intramuscular electroporation of tetravalent DNA vaccines. PlosOne. 2014; 9: 1-6.
Expression and function of Toll-like receptors on dendritic cells and other antigen presenting cells from non-human primates. Vet Immunol Immunopathol. 2008; 125(1-2): 18-30.