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

Denise Haslwanter, Department of Microbiology and Immunology, Albert Einstein College of Medicine, The Bronx, NY 10461, USA.
Gorka Lasso, Department of Microbiology and Immunology, Albert Einstein College of Medicine, The Bronx, NY 10461, USA.
Anna Z. Wec, Adimab, LLC, Lebanon, NH 03766, USA.
Nathália Dias Furtado, Laboratório de Biologia Molecular de Flavivírus, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, 21040-360 Rio de Janeiro, Brazil.
Lidiane Menezes Raphael, Laboratório de Biologia Molecular de Flavivírus, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, 21040-360 Rio de Janeiro, Brazil.
Alexandra L. Tse, Department of Microbiology and Immunology, Albert Einstein College of Medicine, The Bronx, NY 10461, USA.
Yan Sun, Department of Biochemistry, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Stephanie Stransky, Department of Biochemistry, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Núria Pedreño-Lopez, Department of Pathology, The George Washington University, Washington, DC 20037, USA.
Carolina Argondizo Correia, Laboratório de Imunologia Clínica e Alergia, Faculdade de Medicina, Universidade de São Paulo, 01246-903 São Paulo, Brazil.
Zachary A. Bornholdt, Mapp Biopharmaceutical, Inc., San Diego, CA 92121, USA.
Mrunal Sakharkar, Adimab, LLC, Lebanon, NH 03766, USA.
Vivian I. Avelino-Silva, Departamento de Moléstias Infecciosas e Parasitárias, Faculdade de Medicina, Universidade de São Paulo, 01246-903 São Paulo, Brazil.
Crystal L. Moyer, Mapp Biopharmaceutical, Inc., San Diego, CA 92121, USA.
David I. Watkins, Department of Pathology, The George Washington University, Washington, DC 20037, USA.
Esper G. Kallas, Departamento de Moléstias Infecciosas e Parasitárias, Faculdade de Medicina, Universidade de São Paulo, 01246-903 São Paulo, Brazil.
Simone Sidoli, Department of Biochemistry, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Laura M. Walker, Adimab, LLC, Lebanon, NH 03766, USA; Adagio Therapeutics Inc., Waltham, MA 02451, USA.
Myrna C. Bonaldo, Laboratório de Biologia Molecular de Flavivírus, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, 21040-360 Rio de Janeiro, Brazil. Electronic address: mbonaldo@ioc.fiocruz.br.
Kartik Chandran, Department of Microbiology and Immunology, Albert Einstein College of Medicine, The Bronx, NY 10461, USA. Electronic address: kartik.chandran@einsteinmed.edu.

Document Type

Journal Article

Publication Date

2-9-2022

Journal

Cell host & microbe

Volume

30

Issue

2

DOI

10.1016/j.chom.2021.12.009

Keywords

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

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.

Department

Pathology

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