Genotype-specific features reduce the susceptibility of South American yellow fever virus strains to vaccine-induced antibodies

Denise Haslwanter, Gorka Lasso, Anna Z. Wec, Nathália Dias Furtado, Lidiane Menezes Souza Raphael, Alexandra L. Tse, Yan Sun, Stephanie Stransky, Núria Pedreño-Lopez, Carolina Argondizo Correia, Zachary A. Bornholdt, Mrunal Sakharkar, Vivian I. Avelino-Silva, Crystal L. Moyer, David I. Watkins, Esper G. Kallas, Simone Sidoli, Laura M. Walker, Myrna C. Bonaldo, Kartik Chandran

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

The resurgence of yellow fever in South America has prompted vaccination against the etiologic agent, yellow fever virus (YFV). Current vaccines are based on a live-attenuated YF-17D virus derived from a virulent African isolate. The capacity of these vaccines to induce neutralizing antibodies against the vaccine strain is used as a surrogate for protection. However, the sensitivity of genetically distinct South American strains to vaccine-induced antibodies is unknown. We show that antiviral potency of the polyclonal antibody response in vaccinees is attenuated against an emergent Brazilian strain. This reduction was attributable to amino acid changes at two sites in central domain II of the glycoprotein E, including multiple changes at the domain I–domain II hinge, which are unique to and shared among most South American YFV strains. Our findings call for a reevaluation of current approaches to YFV immunological surveillance in South America and suggest approaches for updating vaccines.

Original languageEnglish (US)
Pages (from-to)248-259.e6
JournalCell Host and Microbe
Volume30
Issue number2
DOIs
StatePublished - Feb 9 2022

Keywords

  • 17D
  • South America
  • antibody response
  • emerging virus
  • flavivirus
  • glycoprotein
  • immunological response
  • neutralizing antibodies
  • vaccine
  • yellow fever virus

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Virology

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