A tetravalent nanoparticle vaccine elicits a balanced and potent immune response against dengue viruses without inducing antibody-dependent enhancement

Front Immunol. 2023 May 19:14:1193175. doi: 10.3389/fimmu.2023.1193175. eCollection 2023.

Abstract

Dengue fever is a global health threat caused by the dengue virus (DENV), a vector-borne and single-stranded RNA virus. Development of a safe and efficacious vaccine against DENV is a demanding challenge. The greatest pitfall in the development of vaccines is antibody-dependent enhancement (ADE), which is closely associated with disease exacerbation. We displayed the modified envelope proteins from the four serotypes of the DENV on a 24-mer ferritin nanoparticle, respectively. This tetravalent nanoparticle vaccine induced potent humoral and cellular immunity in mice without ADE and conferred efficient protection against the lethal challenge of DENV-2 and DENV-3 in AG6 mice. Further exploration of immunization strategies showed that even single-dose vaccination could reduce pathologic damage in BALB/c mice infected with high doses of DENV-2. Treatment with cyclic-di-guanosine monophosphate facilitated a higher titer of neutralizing antibodies and a stronger type-1 T-helper cell-biased immune response, thereby revealing it to be an effective adjuvant for dengue nanoparticle vaccines. These data suggest that a promising tetravalent nanoparticle vaccine could be produced to prevent DENV infection.

Keywords: ADE; DENV; adjuvant; ferritin; nanoparticle vaccine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Viral
  • Antibody-Dependent Enhancement
  • Dengue Vaccines*
  • Dengue Virus*
  • Dengue*
  • Immunity, Cellular
  • Mice
  • Mice, Inbred BALB C
  • Nanoparticles*
  • Vaccines, Combined / pharmacology
  • Viral Envelope Proteins

Substances

  • Antibodies, Viral
  • Dengue Vaccines
  • Vaccines, Combined
  • Viral Envelope Proteins

Grants and funding

This work was supported by the National Key R&D Program of Department of Science and Technology of China (2022YFC0870700), Important Key Program of Natural Science Foundation of China (NSFC) (92169201), Exchange Program of NSFC (82150710553), Emergency Key Program of Guangzhou National Laboratory (EKPG21-24), and the Key R&D Program of Department of Science and Technology of Guangdong (2022B1111020004) to HZ. This work was also supported by National Natural Science Foundation of China (82202029) to RC.