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

• Autor(es): Costa-Pereira, Christiane ; Campi-Azevedo, Ana Carolina ; Coelho-dos-Reis, Jordana Grazziela ; Peruhype-Magalh?es, Vanessa ; Ara?jo, M?rcio Sobreira Silva ; Antonelli, Lis Ribeiro do Vale ; Fonseca, Cristina Toscano ; Lemos, Jandira Aparecida ; Malaquias, Luiz Cosme Cote ; Gomes, Matheus de Souza ; Amaral, Laurence Rodrigues ; Rios, Maria ; Chancey, Caren ; Persi, Harold Richard ; Pereira, Jorge Marcelo ; Maia, Maria de Lourdes de Sousa ; Freire, Marcos da Silva ; Martins, Reinaldo de Menezes ; Homma, Akira ; Sim?es, Marisol ; Yamamura, Anna Yoshida ; Farias, Roberto Henrique Guedes ; Romano, Alessandro Pecego Martins ; Domingues, Carla Magda ; Tauil, Pedro Luiz ; Vasconcelos, Pedro Fernando da Costa ; Caldas, Iramaya Rodrigues ; Camacho, Luiz Ant?nio ; Teixeira-Carvalho, Andrea ; Martins Filho, Olindo Assis
• Data: 2018
• Origem: Oasisbr
• Assunto(s): Febre Amarela / imunologia; Vacina contra Febre Amarela; Biomarcadores / an?lise; Citotoxinas; Linf?citos T Reguladores / imunologia; Linf?citos B / imunologia; Mem?ria Imunol?gica; Imunidade Adaptativa
• Tipo de Documento: Artigo científico
• Idioma: Inglês

Descrição

Programa Nacional de Imuniza??es (PNI), Secretaria de Vigil?ncia em Sa?de (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.

Funda??o Oswaldo Cruz. Centro de Pesquisas Ren? Rachou. Belo Horizonte, MG, Brazil.

Funda??o Oswaldo Cruz. Centro de Pesquisas Ren? Rachou. Belo Horizonte, MG, Brazil.

Funda??o Oswaldo Cruz. Centro de Pesquisas Ren? Rachou. Belo Horizonte, MG, Brazil.

Funda??o Oswaldo Cruz. Centro de Pesquisas Ren? Rachou. Belo Horizonte, MG, Brazil.

Funda??o Oswaldo Cruz. Centro de Pesquisas Ren? Rachou. Belo Horizonte, MG, Brazil.

Funda??o Oswaldo Cruz. Centro de Pesquisas Ren? Rachou. Belo Horizonte, MG, Brazil.

Funda??o Oswaldo Cruz. Centro de Pesquisas Ren? Rachou. Belo Horizonte, MG, Brazil.

Governo do Estado de Minas Gerais. Secretaria de Estado de Sa?de. Belo Horizonte, MG, Brasil.

Universidade Federal de Alfenas. Alfenas, MG, Brazil.

Universidade Federal de Uberl?ndia. Laborat?rio de Bioinform?tica e An?lises Moleculares. Uberl?ndia, MG, Brazil.

Universidade Federal de Uberl?ndia. Laborat?rio de Bioinform?tica e An?lises Moleculares. Uberl?ndia, MG, Brazil.

Food and Drug Administration. Center for Biologics Evaluation and Research. Silver Spring, Maryland, USA.

Food and Drug Administration. Center for Biologics Evaluation and Research. Silver Spring, Maryland, USA.

Instituto de Biologia do Ex?rcito. Rio de Janeiro, RJ, Brazil.

Instituto de Biologia do Ex?rcito. Rio de Janeiro, RJ, Brazil.

Funda??o Oswaldo Cruz. Instituto de Tecnologia em Imunobiol?gicos Bio-Manguinhos. Rio de Janeiro, RJ, Brazil.

Funda??o Oswaldo Cruz. Instituto de Tecnologia em Imunobiol?gicos Bio-Manguinhos. Rio de Janeiro, RJ, Brazil.

Funda??o Oswaldo Cruz. Instituto de Tecnologia em Imunobiol?gicos Bio-Manguinhos. Rio de Janeiro, RJ, Brazil.

Funda??o Oswaldo Cruz. Instituto de Tecnologia em Imunobiol?gicos Bio-Manguinhos. Rio de Janeiro, RJ, Brazil.

Funda??o Oswaldo Cruz. Instituto de Tecnologia em Imunobiol?gicos Bio-Manguinhos. Rio de Janeiro, RJ, Brazil.

Funda??o Oswaldo Cruz. Instituto de Tecnologia em Imunobiol?gicos Bio-Manguinhos. Rio de Janeiro, RJ, Brazil.

Funda??o Oswaldo Cruz. Instituto de Tecnologia em Imunobiol?gicos Bio-Manguinhos. Rio de Janeiro, RJ, Brazil.

Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Bras?lia, DF, Brazil.

Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Bras?lia, DF, Brazil.

Universidade de Bras?lia, Bras?lia. Bras?lia, DF, Brazil.

Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil.

Funda??o Oswaldo Cruz. Diretoria Regional de Bras?lia. Bras?lia, DF, Brazil.

Funda??o Oswaldo Cruz. Escola Nacional de Sa?de P?blica, Rio de Janeiro, RJ, Brazil.

Funda??o Oswaldo Cruz. Centro de Pesquisas Ren? Rachou. Belo Horizonte, MG, Brazil.

Funda??o Oswaldo Cruz. Centro de Pesquisas Ren? Rachou. Belo Horizonte, MG, Brazil.

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 (Na?ve/early-effector/Central-Memory/Effector-Memory) and B-cells (Na?ve/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.