In December 2019

Dengue virus (DENV) has become a global health threat with about half of the world’s population at risk of infection. Although the disease caused by DENV is self-limiting in the first infection, the antibody-dependent enhancement (ADE) effect increases the mortality in the second infection with a heterotypic virus. Since there is no specific efficient medicine in treatment, it is urgent to develop vaccines to prevent infection and disease progression. Currently, only a live attenuated vaccine, chimeric yellow fever 17D—tetravalent dengue vaccine (CYD-TDV), has been licensed for clinical use in some countries, and many candidate vaccines are still under research and development. This review discusses the progress, strengths, and weaknesses of the five types of vaccines including live attenuated vaccine, inactivated virus vaccine, recombinant subunit vaccine, viral vectored vaccine, and DNA vaccine.

A large outbreak of dengue, with the most documented cases, occurred in Guangdong China in 2014. Epidemiological studies and phylogenetic analysis of the isolated dengue virus (DENV) showed this outbreak was attributed to multiple sources and caused by at least two genotypes of DENV-1 (Genotypes I and III) and two genotypes of DENV-2 (Cosmopolitan and Asian I Genotypes). A retrospective review and phylogenetic analysis of DENV isolated in Guangdong showed that DENV-1 Genotype I strains were reported continuously during 2004–2014, Genotype III strains were reported during 2009–2014 ; DENV-2 Cosmopolitan and Asian I Genotype strains were reported continuously during 2012–2014. At least 45,171 cases were reported in this outbreak, with 65.9% of the patients in the 21–55-year-old group. A trend toward a decrease in the daily newly emerged cases lagged by approximately 20 days compared with the mosquito density curve. Several epidemiological characteristics of this outbreak and the stably sustained serotypes and genotypes of DENV isolated in Guangdong suggest that Guangdong has been facing a threat of transforming from a dengue epidemic area to an endemic area. The high temperature, drenching rain, rapid urbanization, and pandemic of dengue in Southeast Asia may have contributed to this large outbreak of dengue.

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Background The entomopathogenic fungus Beauveria bassiana has been widely used to kill mosquito larvae and adults in the laboratory and field. However, its slow action of killing has hampered its widespread application. In our study, the B . bassiana fungus was genetically modified to express the Bacillus thuringiensis (Bt) toxin Cyt2Ba to improve its efficacy in killing mosquitoes. Methodology/Principal findings The efficacy of the wild type (WT) of B . bassiana and a transgenic strain expressing Cyt2Ba toxin ( Bb -Cyt2Ba) was evaluated against larval and adult Aedes mosquitoes ( Aedes aegypti and Aedes albopictus ) using insect bioassays. The Bb -Cyt2Ba displayed increased virulence against larval and adult Aedes mosquitoes compared with the WT: for Ae . aegypti adults, the median lethal time (LT 50 ) was decreased by 33% at the concentration of 1× 10 8 conidia/ml, 19% at 1× 10 7 conidia/ml and 47% at 1× 10 6 conidia/ml. The LT 50 for Ae . albopictus adults was reduced by 20%, 23% and 29% at the same concentrations, respectively. The LT 50 for Ae . aegypti larvae was decreased by 42% at 1× 10 7 conidia/ml and 25% at 1× 10 6 conidia/ml, and that for Ae . albopictus larvae was reduced by 33% and 31% at the same concentrations, respectively. In addition, infection with Bb -Cyt2Ba resulted in a dramatic reduction in the fecundity of Aedes mosquitoes. Conclusions/Significance In conclusion, our study demonstrated that the virulence of B . bassiana against mosquitoes can be significantly improved by introducing the Bt toxin gene Cyt2Ba into the genome to express the exogenous toxin in the fungus. The transgenic strain Bb -Cyt2Ba significantly reduced the survival and fecundity of Ae . aegypti and Ae . albopictus compared with the WT strain, which suggested that this recombinant B . bassiana has great potential for use in mosquito control.