New Anti-Flavivirus Fusion Loop Human Antibodies with Zika Virus-Neutralizing Potential

Int J Mol Sci. 2022 Jul 15;23(14):7805. doi: 10.3390/ijms23147805.

Abstract

Zika virus infections exhibit recurrent outbreaks and can be responsible for disease complications such as congenital Zika virus syndrome. Effective therapeutic interventions are still a challenge. Antibodies can provide significant protection, although the antibody response may fail due to antibody-dependent enhancement reactions. The choice of the target antigen is a crucial part of the process to generate effective neutralizing antibodies. Human anti-Zika virus antibodies were selected by phage display technology. The antibodies were selected against a mimetic peptide based on the fusion loop region in the protein E of Zika virus, which is highly conserved among different flaviviruses. Four rounds of selection were performed using the synthetic peptide in two strategies: the first was using the acidic elution of bound phages, and the second was by applying a competing procedure. After panning, the selected VH and VL domains were determined by combining NGS and bioinformatic approaches. Three different human monoclonal antibodies were expressed as scFvs and further characterized. All showed a binding capacity to Zika (ZIKV) and showed cross-recognition with yellow fever (YFV) and dengue (DENV) viruses. Two of these antibodies, AZ1p and AZ6m, could neutralize the ZIKV infection in vitro. Due to the conservation of the fusion loop region, these new antibodies can potentially be used in therapeutic intervention against Zika virus and other flavivirus illnesses.

Keywords: Zika virus; fusion loop; monoclonal antibody; neutralization; phage display.

MeSH terms

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Cross Reactions
  • Dengue Virus*
  • Dengue*
  • Flavivirus*
  • Humans
  • Zika Virus Infection*
  • Zika Virus*

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral

Grants and funding

This research was supported by grants and scholarships from the Research Support Foundation of the Federal District (FAPDF 00193.0000.1054/2021-79), Coordination for the Improvement of Higher Education Personnel (CAPES 88887.513930/2020-00), and the Brazilian National Council for Scientific and Technological Development (CNPq).