Dengue virus(DENV)is a mosquito-borne virus with a rapid spread to humans,causing mild to potentially fatal illness in hundreds of millions of people each year.Due to the large number of serotypes of the virus,there r...Dengue virus(DENV)is a mosquito-borne virus with a rapid spread to humans,causing mild to potentially fatal illness in hundreds of millions of people each year.Due to the large number of serotypes of the virus,there remains an unmet need to develop protective vaccines for a broad spectrum of the virus.Here,we constructed a modified mRNA vaccine containing envelope domain III(E-DIII)and non-structural protein 1(NS1)coated with lipid nanoparticles.This multi-target vaccine induced a robust antiviral immune response and increased neutralizing antibody titers that blocked all four types of DENV infection in vitro without significant antibodydependent enhancement(ADE).In addition,there was more bias for Th1 than Th2 in the exact E-DIII and NS1-specific T cell responses after a single injection.Importantly,intramuscular immunization limited DENV transmission in vivo and eliminated vascular leakage.Our findings highlight that chimeric allogeneic structural and non-structural proteins can be effective targets for DENV vaccine and that they can prevent the further development of congenital DENV syndrome.展开更多
基金supported by the Strategic Priority Research Program of CAS (XDB29010000)partially financially supported by the Institute of Infectious Disease of Shenzhen Bay Laboratorysupported by the Youth Innovation Promotion Association of CAS (2019091)
文摘Dengue virus(DENV)is a mosquito-borne virus with a rapid spread to humans,causing mild to potentially fatal illness in hundreds of millions of people each year.Due to the large number of serotypes of the virus,there remains an unmet need to develop protective vaccines for a broad spectrum of the virus.Here,we constructed a modified mRNA vaccine containing envelope domain III(E-DIII)and non-structural protein 1(NS1)coated with lipid nanoparticles.This multi-target vaccine induced a robust antiviral immune response and increased neutralizing antibody titers that blocked all four types of DENV infection in vitro without significant antibodydependent enhancement(ADE).In addition,there was more bias for Th1 than Th2 in the exact E-DIII and NS1-specific T cell responses after a single injection.Importantly,intramuscular immunization limited DENV transmission in vivo and eliminated vascular leakage.Our findings highlight that chimeric allogeneic structural and non-structural proteins can be effective targets for DENV vaccine and that they can prevent the further development of congenital DENV syndrome.
