Scientific Publications by FDA Staff

PLoS Negl Trop Dis 2018 Jun 7;12(6):e0006462

Multi-parameter approach to evaluate the timing of memory status after 17DD-YF primary vaccination.

Costa-Pereira C, Campi-Azevedo AC, Coelho-Dos-Reis JG, Peruhype-Magalhaes V, Araujo MSS, do Vale Antonelli LR, Fonseca CT, Lemos JA, Malaquias LCC, de Souza Gomes M, Rodrigues Amaral L, Rios M, Chancey C, Persi HR, Pereira JM, de Sousa Maia ML, Freire MDS, Martins RM, Homma A, Simoes M, Yamamura AY, Farias RHG, Romano APM, Domingues CM, Tauil PL, Vasconcelos PFC, Caldas IR, Camacho LA, Teixeira-Carvalho A, Martins-Filho OA

In this investigation, machine-enhanced techniques were applied to bring about scientific insights to identify a minimum set of phenotypic/functional memory-related biomarkers for post-vaccination follow-up upon yellow fever (YF) vaccination. For this purpose, memory status of circulating T-cells (Naive/early-effector/Central-Memory/Effector-Memory) and B-cells (Naive/non-Classical-Memory/Classical-Memory) along with the cytokine profile (IFN/TNF/IL-5/IL-10) were monitored before-NV(day0) and at distinct time-points after 17DD-YF primary vaccination-PV(day30-45); PV(year1-9) and PV(year10-11). A set of biomarkers (eEfCD4; EMCD4; CMCD19; EMCD8; IFNCD4; IL-5CD8; TNFCD4; IFNCD8; TNFCD8; IL-5CD19; IL-5CD4) were observed in PV(day30-45), but not in NV(day0), with most of them still observed in PV(year1-9). Deficiencies of phenotypic/functional biomarkers were observed in NV(day0), while total lack of memory-related attributes was observed in PV(year10-11), regardless of the age at primary vaccination. Venn-diagram analysis pre-selected 10 attributes (eEfCD4, EMCD4, CMCD19, EMCD8, IFNCD4, IL-5CD8, TNFCD4, IFNCD8, TNFCD8 and IL-5CD4), of which the overall mean presented moderate accuracy to discriminate PV(day30-45)&PV(year1-9) from NV(day0)&PV(year10-11). Multi-parameter approaches and decision-tree algorithms defined the EMCD8 and IL-5CD4 attributes as the top-two predictors with moderated performance. Together with the PRNT titers, the top-two biomarkers led to a resultant memory status observed in 80% and 51% of volunteers in PV(day30-45) and PV(year1-9), contrasting with 0% and 29% found in NV(day0) and PV(year10-11), respectively. The deficiency of memory-related attributes observed at PV(year10-11) underscores the conspicuous time-dependent decrease of resultant memory following17DD-YF primary vaccination that could be useful to monitor potential correlates of protection in areas under risk of YF transmission.