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Citation: Lihong He, Wenqiang Sun, Limin Yang, Wenjun Liu, Jing Li. A multiple-target mRNA-LNP vaccine induces protective immunity against experimental multi-serotype DENV in mice [J].VIROLOGICA SINICA, 2022, 37(5) : 746-757.  http://dx.doi.org/10.1016/j.virs.2022.07.003

A multiple-target mRNA-LNP vaccine induces protective immunity against experimental multi-serotype DENV in mice

  • Corresponding author: Wenjun Liu, liuwj@im.ac.cn
    Jing Li, lj418@163.com
  • Received Date: 15 April 2022
    Accepted Date: 04 July 2022
    Available online: 12 July 2022
  • 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 antibody-dependent 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.

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    A multiple-target mRNA-LNP vaccine induces protective immunity against experimental multi-serotype DENV in mice

      Corresponding author: Wenjun Liu, liuwj@im.ac.cn
      Corresponding author: Jing Li, lj418@163.com
    • a CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, China;

    Abstract: 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 antibody-dependent 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.

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