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

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. [Display omitted] • YFV vaccine-induced neutralization is attenuated against South American YFV strains • Reduced neutralization sensitivity genetically maps to domain II of the E protein • Multiple genetic changes in domain I–domain II hinge affect antibody recognition • Approach to YFV immunological surveillance in South America should be reevaluated Yellow fever vaccines based on an African strain induce neutralizing antibodies that are associated with protection. Haslwanter et al. show that these antibodies have reduced activity against South American strains because hey bear genetically distinct surface proteins, suggesting that changes are needed in how immune protection against YFV is monitored. [ABSTRACT FROM AUTHOR]