Travel-acquired dengue cases have been increasing as the overall global dengue burden has expanded. In Korea, imported dengue cases have been reported since 2000 when it first became a notifiable disease. During the first four months of 2016, three times more dengue cases were reported in Korea than during the same period the previous year. A safe and efficacious vaccine for travelers would be beneficial to prevent dengue disease in individual travelers and potentially decrease the risk of virus spread to non-endemic areas. Here, we summarize the characteristics of dengue vaccines for travelers and review dengue vaccines currently licensed or in clinical development.
Dengue Vaccines* ; Dengue* ; Korea

Dengue vaccine development has been one of the strategies to reduce dengue incidence in the world alongside with other horizontal interventions such as vector control and the transgenic mosquito programmes. The objective of this paper is to evaluate the safety, reactogenicity and immunogenicity of dengue vaccine clinical trials for the last ten years systematically through a descriptive review. This paper discusses safety issues like adverse events, systemic adverse reactions, injection site reactions, viraemia, morbidity and mortality as well as immunogenicity which measures effectiveness through mean geometric titre and seropositive rates. Adverse events were seen to range from 0% to 28.3%. Immunogenicity was noted to increase post 1st and 2nd dose and decrease post 3rd dose. The seropositivity at baseline ranged between 53.1% and 97.8% at post 3rd dose, and it was 88.5% for at least four serotypes. The dengue vaccine studies that were reviewed were shown to be relatively safe with low reactogenicity, however the immunogenicity was unequal and waning. The immunogenicity waned post 3rd dose showing a decrease in all serotypes of varying degrees although the seropositivity, on average, at post 3rd dose was 97.8%. It can be concluded that dengue vaccine development would require further studies on its unequal and waning immunogenicity, which could result in a more severe form of dengue following wild infection, during re-immunisation, especially if there is variation in the circulating virus.
Dengue Vaccines ; Dengue

BACKGROUND: The DOH has recently launched the first ever dengue vaccine that has successfully completed phase III clinical trials but an assessment of the general acceptance of the vaccine is widely lacking. OBJECTIVES: This study determined the dengue vaccine acceptance and the factors associated with acceptance as well as the knowledge, attitudes and practices on dengue fever among parents and caregivers at the PCMC-OPD. METHODS: A hospital-based cross-sectional survey was done at the PCMC-OPD using selfadministered questionnaires regarding the KAP on dengue fever and vaccine acceptance. Multivariate analysis and Spearman’s rank correlation were used to determine predictors of DV acceptance. RESULTS: We found that DV acceptance among the participants was 81.3% (113 out of 139). Educational attainment, employment status, and monthly income are significantly associated with acceptance of dengue vaccine, and being female contributed to high acceptance. DV acceptance was strongly correlated with a lower income class. Educational attainment and employment status seem to affect DV acceptance but are not strong predictors. CONCLUSIONS: The DV acceptance rate of the parents and caregivers of patients consulting at PCMC-OPD was high. The most important factors associated with acceptance are educational attainment, employment status and income class. RECOMMENDATIONS A similar study may be conducted with a larger population to study target populations in the Philippines. This kind of study can be utilized to formulate new strategies addressing the awareness and acceptance of the community for the new dengue vaccine.
Dengue ; Dengue Virus ; Dengue Vaccines ; Philippines

Dengue fever is a tropical endemic disease; however, because of climate change, it may become a problem in South Korea in the near future. Research on vaccines for dengue fever and outbreak preparedness are currently insufficient. In addition, because there are no appropriate animal models, controversial results from vaccine efficacy assessments and clinical trials have been reported. Therefore, to study the mechanism of dengue fever and test the immunogenicity of vaccines, an appropriate animal model is urgently needed. In addition to mouse models, more suitable models using animals that can be humanized will need to be constructed. In this report, we look at the current status of model animal construction and discuss which models require further development.
Animals* ; Climate Change ; Dengue Virus ; Dengue* ; Endemic Diseases ; Humans ; Korea ; Mice ; Models, Animal* ; Vaccines

BACKGROUND: Dengue virus, which belongs to the Flavivirus genus of the Flaviviridae family, causes fatal dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) with infection risk of 2.5 billion people worldwide. However, approved vaccines are still not available. Here, we explored the immune responses induced by alternating prime-boost vaccination using DNA vaccine, adenovirus, and vaccinia virus expressing E protein of dengue virus type 2 (DenV2). METHODS: Following immunization with DNA vaccine (pDE), adenovirus (rAd-E), and/or vaccinia virus (VV-E) expressing E protein, E protein-specific IgG and its isotypes were determined by conventional ELISA. Intracellular CD154 and cytokine staining was used for enumerating CD4+ T cells specific for E protein. E protein-specific CD8+ T cell responses were evaluated by in vivo CTL killing activity and intracellular IFN-gamma staining. RESULTS: Among three constructs, VV-E induced the most potent IgG responses, Th1-type cytokine production by stimulated CD4+ T cells, and the CD8+ T cell response. Furthermore, when the three constructs were used for alternating prime-boost vaccination, the results revealed a different pattern of CD4+ and CD8+ T cell responses. i) Priming with VV-E induced higher E-specific IgG level but it was decreased rapidly. ii) Strong CD8+ T cell responses specific for E protein were induced when VV-E was used for the priming step, and such CD8+ T cell responses were significantly boosted with pDE. iii) Priming with rAd-E induced stronger CD4+ T cell responses which subsequently boosted with pDE to a greater extent than VV-E and rAd-E. CONCLUSION: These results indicate that priming with live viral vector vaccines could induce different patterns of E protein- specific CD4+ and CD8+ T cell responses which were significantly enhanced by booster vaccination with the DNA vaccine. Therefore, our observation will provide valuable information for the establishment of optimal prime-boost vaccination against DenV.
Adenoviridae ; Dengue ; Dengue Hemorrhagic Fever ; Dengue Virus ; DNA ; Enzyme-Linked Immunosorbent Assay ; Flaviviridae ; Flavivirus ; Homicide ; Humans ; Immunity, Cellular ; Immunization ; Immunoglobulin G ; Plasmids ; T-Lymphocytes ; Vaccination ; Vaccines ; Vaccinia virus

BACKGROUND: Dengue virus, which belongs to the Flavivirus genus of the Flaviviridae family, causes fatal dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) with infection risk of 2.5 billion people worldwide. However, approved vaccines are still not available. Here, we explored the immune responses induced by alternating prime-boost vaccination using DNA vaccine, adenovirus, and vaccinia virus expressing E protein of dengue virus type 2 (DenV2). METHODS: Following immunization with DNA vaccine (pDE), adenovirus (rAd-E), and/or vaccinia virus (VV-E) expressing E protein, E protein-specific IgG and its isotypes were determined by conventional ELISA. Intracellular CD154 and cytokine staining was used for enumerating CD4+ T cells specific for E protein. E protein-specific CD8+ T cell responses were evaluated by in vivo CTL killing activity and intracellular IFN-gamma staining. RESULTS: Among three constructs, VV-E induced the most potent IgG responses, Th1-type cytokine production by stimulated CD4+ T cells, and the CD8+ T cell response. Furthermore, when the three constructs were used for alternating prime-boost vaccination, the results revealed a different pattern of CD4+ and CD8+ T cell responses. i) Priming with VV-E induced higher E-specific IgG level but it was decreased rapidly. ii) Strong CD8+ T cell responses specific for E protein were induced when VV-E was used for the priming step, and such CD8+ T cell responses were significantly boosted with pDE. iii) Priming with rAd-E induced stronger CD4+ T cell responses which subsequently boosted with pDE to a greater extent than VV-E and rAd-E. CONCLUSION: These results indicate that priming with live viral vector vaccines could induce different patterns of E protein- specific CD4+ and CD8+ T cell responses which were significantly enhanced by booster vaccination with the DNA vaccine. Therefore, our observation will provide valuable information for the establishment of optimal prime-boost vaccination against DenV.
Adenoviridae ; Dengue ; Dengue Hemorrhagic Fever ; Dengue Virus ; DNA ; Enzyme-Linked Immunosorbent Assay ; Flaviviridae ; Flavivirus ; Homicide ; Humans ; Immunity, Cellular ; Immunization ; Immunoglobulin G ; Plasmids ; T-Lymphocytes ; Vaccination ; Vaccines ; Vaccinia virus

Dengue virus (DENV) is a re-emerging disease transmitted by the Aedes mosquitoes and has become a major public health problem in southern China. Currently, no antiviral drug or effective vaccine exist to control this disease. The chimeric DENV structural protein vaccine cannot elicit balanced levels of protective immunity to each of the four viral serotypes; therefore, non-structural protein components may be required to construct an effective DENV vaccine. The Dengue virus non-structural 1 (DENV NS1) protein plays a critical role in viral pathogenesis and protective immunity. Therefore, immunity to Dengue 1-4 NS1 subtypes may be crucial for the prevention of severe disease. This review attempts to provide an overview about the structure and function of DENV NS1.
Animals ; Dengue ; immunology ; prevention & control ; virology ; Dengue Vaccines ; chemistry ; genetics ; immunology ; Dengue Virus ; chemistry ; genetics ; immunology ; Humans ; Viral Nonstructural Proteins ; chemistry ; genetics ; immunology

Adenoviridae ; genetics ; Animals ; Dengue Vaccines ; immunology ; Humans ; Plasmids ; Recombinant Fusion Proteins ; immunology ; Vaccines, Attenuated ; immunology ; Vaccines, DNA ; immunology ; Vaccines, Synthetic ; immunology

Despite recent advances in the development of diagnostics, therapeutics, and vaccines, the ease of international travel and increasing global interdependence have brought about particular challenges for the control of infectious diseases, highlighting concerns for the worldwide spread of emerging and reemerging infectious diseases. Korea is also facing public health challenges for controlling imported cases of infectious diseases; dengue virus, which is the most commonly reported case of imported infectious diseases; the largest outbreak of Middle East respiratory syndrome coronavirus infections outside the Arabian Peninsula in 2015; and the Zika virus infection, which was declared by the WHO as a "Public Health Emergency of International Concern." Although national and global partnerships are critical to controlling imported infectious disease threats, the role of local hospitals, public health sectors, and laboratory capacity remains the cornerstone for initial disease recognition and response. The current status of laboratory diagnosis for imported infectious diseases is reviewed.
Clinical Laboratory Techniques ; Communicable Diseases ; Communicable Diseases, Emerging* ; Coronavirus Infections ; Dengue ; Dengue Virus ; Diagnosis* ; Emergencies ; Hospitals, Public ; Korea* ; Middle East ; Public Health ; Vaccines

Despite recent advances in the development of diagnostics, therapeutics, and vaccines, the ease of international travel and increasing global interdependence have brought about particular challenges for the control of infectious diseases, highlighting concerns for the worldwide spread of emerging and reemerging infectious diseases. Korea is also facing public health challenges for controlling imported cases of infectious diseases; dengue virus, which is the most commonly reported case of imported infectious diseases; the largest outbreak of Middle East respiratory syndrome coronavirus infections outside the Arabian Peninsula in 2015; and the Zika virus infection, which was declared by the WHO as a "Public Health Emergency of International Concern." Although national and global partnerships are critical to controlling imported infectious disease threats, the role of local hospitals, public health sectors, and laboratory capacity remains the cornerstone for initial disease recognition and response. The current status of laboratory diagnosis for imported infectious diseases is reviewed.
Clinical Laboratory Techniques ; Communicable Diseases ; Communicable Diseases, Emerging* ; Coronavirus Infections ; Dengue ; Dengue Virus ; Diagnosis* ; Emergencies ; Hospitals, Public ; Korea* ; Middle East ; Public Health ; Vaccines