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

PLoS Negl Trop Dis. 2018 Jun 7;12(6):e0006462. doi: 10.1371/journal.pntd.0006462. eCollection 2018 Jun.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antibodies, Viral / blood*
  • B-Lymphocytes / immunology
  • Biomarkers / blood*
  • CD8-Positive T-Lymphocytes / immunology
  • Cytokines / blood
  • Humans
  • Male
  • Middle Aged
  • Time Factors
  • Vaccination*
  • Yellow Fever / immunology
  • Yellow Fever / prevention & control*
  • Yellow Fever / virology
  • Yellow Fever Vaccine / immunology*
  • Yellow fever virus / immunology*
  • Young Adult

Substances

  • Antibodies, Viral
  • Biomarkers
  • Cytokines
  • Yellow Fever Vaccine

Grants and funding

The authors thank the Programa Nacional de Imunizações (PNI), Secretaria de Vigilância em Saúde (SVS), PDTIS, CNPq (472782/2009-6 and 475076/2013-3), CAPES, FAPEMIG and PROEP/CPqRR/FIOCRUZ for financial support. ACCA and JGCdR received financial support from CNPq MCTI/CNPq/2014. The authors are thankful to the Programa de Desenvolvimento Tecnológico em Insumos para a Saúde -PDTIS-FIOCRUZ for the use of the flow cytometry facilities and the Programa de Pós-Graduação em Ciências da Saúde. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.