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Development of new TB vaccine candidates with multivalent antigens
Identification of surrogate markers to assess the immunological efficacy of TB vaccines
The development of new vaccines against TB remains hampered by the difficulty in evaluating their efficacy. To identify potential biomarkers to evaluate vaccine efficacy as well as to understand host immune response, we assessed cytokine profiles and gene expression among individuals with active TB and latent infection, as well as those in healthy controls (HCs). M. tuberculosis-specific antigen-induced and unstimulated cytokines were measured by multiplexed cytokine assays in these individuals. Among the 27 cytokines, 11 biomarkers in the HCs differed significantly from those in the M. tuberculosis-infected group. We also conducted a microarray experiment to compare the gene expression profiles in peripheral blood mononuclear cells. Bioinformatic analysis revealed that most of the differentially expressed genes were associated with immune responses, inflammation pathways, and cell cycle control. Validation in a larger sample size is necessary to confirm the reliability of the biomarkers and facilitate the development of biomarkers to evaluate vaccine efficacy.
Screening of efficient antigenic candidates against variants of mumps viruses (MuV)
Mumps caused MuV is a vaccine-preventable disease. Since the MMR vaccine was incorporated into the National Immunization program in Korea in 1985, the incidence of mumps has declined. However, mumps outbreaks still occur in vaccinated children because of waning immunity or antigenic differences between the vaccine strain and circulating wild-type viruses. To investigate this concern, we have analysed the genetic characteristics of the hemagglutinin-neuraminidase (HN) gene of MuV isolated in Korea (Figure 1). We will next generate recombinant adenoviruses expressing individual antigens of various genotypes. Our goal is to provide vaccine antigen candidates for protection against diverse MuV genotypes and evaluation of their efficacy.
Figure 1. Phylogenetic tree of mumps viruses (MuVs)
Development of a Zika vaccine based on a rapid vaccine development platform
Following the ZIKV epidemic in 2015–2016, ZIKV infection in pregnant women was shown to potentially result in congenital Zika syndromes such as microcephaly and severe brain malfunctions in the infant. Zika can be transmitted by mosquitos and by infected individuals through sexual contact. The difficulties of disease control and irreversible foetal defects increase the importance and urgency of vaccine development. To develop a vaccine, we applied the viral vector and DNA vaccine platform, which are appropriate for rapid vaccine development against emerging infectious diseases. Four vaccinia viral vectors and adenoviral vectors expressing Zika viral antigens such as prM/E, E, and partial E were constructed, and recombinant viruses were cultured. In addition, 16 recombinant DNA vaccine candidates expressing prM/E, E, or various combination of partial E gene were also produced. The in vitro expression efficacy of these various constructs in cell lines were tested, and candidates showing little antigen expression were excluded from further analysis. We analysed the epitopes of E protein in humanized mice to overcome the limitations of mouse experiments, and the domain III of the E protein C-terminal region showed a high level of antigenicity in ELISPOT assays. We will next analyse the levels of neutralizing antibodies and antigen-specific B/T cell immune responses in immunocompetent mice. Based on this T-cell epitope region and neutralizing antibody-inducing domain, final efficient candidates will be selected and further evaluated in animal challenge models.
Korea Vaccine Research Centre (VRC)
The VRC will conduct a comprehensive vaccine research and development program for national health improvement. The primary research focus will be the development of vaccines for pandemic infectious diseases and bioterrorism. In addition, the VRC will provide nonclinical evaluation of vaccine candidate materials as well as collection and management services for vaccine candidates. The VRC building is scheduled to be completed by 2020. We established the preliminary design of the VRC building in December 2017 (Figure 2). Currently, the enforcement design is underway with an aim to start construction in the autumn 2018.
Figure 2. Preliminary design of the Korea Vaccine Research Center