PLoS Neglected Tropical Diseases (Jun 2018)

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

  • Christiane Costa-Pereira,
  • Ana Carolina Campi-Azevedo,
  • Jordana Grazziela Coelho-Dos-Reis,
  • Vanessa Peruhype-Magalhães,
  • Márcio Sobreira Silva Araújo,
  • Lis Ribeiro do Vale Antonelli,
  • Cristina Toscano Fonseca,
  • Jandira Aparecida Lemos,
  • Luiz Cosme Cote Malaquias,
  • Matheus de Souza Gomes,
  • Laurence Rodrigues Amaral,
  • Maria Rios,
  • Caren Chancey,
  • Harold Richard Persi,
  • Jorge Marcelo Pereira,
  • Maria de Lourdes de Sousa Maia,
  • Marcos da Silva Freire,
  • Reinaldo de Menezes Martins,
  • Akira Homma,
  • Marisol Simões,
  • Anna Yoshida Yamamura,
  • Roberto Henrique Guedes Farias,
  • Alessandro Pecego Martins Romano,
  • Carla Magda Domingues,
  • Pedro Luiz Tauil,
  • Pedro Fernando Costa Vasconcelos,
  • Iramaya Rodrigues Caldas,
  • Luiz Antônio Camacho,
  • Andrea Teixeira-Carvalho,
  • Olindo Assis Martins-Filho

DOI
https://doi.org/10.1371/journal.pntd.0006462
Journal volume & issue
Vol. 12, no. 6
p. e0006462

Abstract

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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 (Naïve/early-effector/Central-Memory/Effector-Memory) and B-cells (Naïve/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.