Differential Neutralization Profiles of 17DD Vaccinated Population to 17D-204 and 17DD Vaccine Strains

Abstract

Background/Objectives: Yellow fever virus (YFV) (Flaviviridae, Orthoflavivirus) is the etiologic agent of yellow fever (YF), a vector-borne disease with significant morbidity and mortality across the tropics and neotropics, despite having a highly efficacious and safe vaccine (17D). Vaccination provides lifelong protection from YF disease mediated by humoral immunity. There are several versions of the original 17D vaccine: 17D-204 (marketed in the USA as YF-VAX, in France as Stamaril, and in China as Tiantan-V), 17D-213 (Russian Federation), and 17DD (by FIOCRUZ in Brazil). Vaccines produced in the US, France, Senegal, China, and Russia represent 17D-204-derived strains, whereas the Brazilian 17DD has a unique passage/attenuation history from 17D-204-derived strains. Their functional differences in the neutralization profiles are not known. Methods: The Plaque Reduction Neutralization Test (PRNT) was used to determine the neutralization profiles of sera from 209 patients that were previously vaccinated with the 17DD strain against both 17D-204 and 17DD. Results: Sera exhibited significantly more efficient neutralization of 17DD (mean reciprocal PRNT₅₀ 183, PRNT₈₀ 86, median reciprocal PRNT₅₀ 80, and PRNT₈₀ 40) compared to 17D-204 (mean reciprocal PRNT₅₀ 91, PRNT₈₀ 33, median reciprocal PRNT₅₀ 40, and PRNT₈₀ 10). Conclusions: Our data indicate antigenic differences between 17D and 17DD vaccines.

Keywords: YFV; immune response; neutralizing antibodies; vaccine.

Figure 1

Reciprocal Plaque Reduction Neutralization Test (PRNT) titers of the study population. Reciprocal neutralization titers of the 209 serum samples against either YFV 17D-204 or 17DD. (A) Representation of 50% neutralization titer against designated vaccine strain. (B) Representation of 50% neutralization titer against designated vaccine strain. Bold lines within the boxes represent median values. Between-group comparisons were made using the nonparametric Mann–Whitney test to detect differences in median values. **** p < 0.0001.