Vaccine-induced antibodies to contemporary strains of dengue virus type 4 show a mechanistic correlate of protective immunity

Cell Rep. 2022 Jun 7;39(10):110930. doi: 10.1016/j.celrep.2022.110930.

Abstract

The four dengue virus serotypes (DENV1-4) are mosquito-borne flaviviruses of humans. Several live-attenuated tetravalent DENV vaccines are at different stages of clinical development and approval. In children with no baseline immunity to DENVs, a leading vaccine (Dengvaxia) is efficacious against vaccine-matched DENV4 genotype II (GII) strains but not vaccine-mismatched DENV4 GI viruses. We use a panel of recombinant DENV4 viruses displaying GI or GII envelope (E) proteins to map Dengvaxia-induced neutralizing antibodies (NAbs) linked to protection. The vaccine stimulated antibodies that neutralize the DENV4 GII virus better than the GI virus. The neutralization differences map to 5 variable amino acids on the E protein located within a region targeted by DENV4 NAbs, supporting a mechanistic role for these epitope-specific NAbs in protection. In children with no baseline immunity to DENVs, levels of DENV4 serotype- and genotype-specific NAbs induced by vaccination are predictive of vaccine efficacy.

Keywords: CP: Immunology; antibodies; dengue virus; immune correlate; live-attenuated tetravalent dengue vaccine; vaccines.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Child
  • Dengue Virus* / genetics
  • Dengue*
  • Epitopes
  • Humans

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Epitopes