title: 17DD and 17D-213/77 yellow fever substrains trigger a balanced cytokine profile in primary vaccinated children.
abstract: BACKGROUND
  This study aimed to compare the cytokine-mediated immune response in children submitted to primary vaccination with the YF-17D-213/77 or YF-17DD yellow fever (YF) substrains.
  
  
  METHODS
  A non-probabilistic sample of eighty healthy primary vaccinated (PV) children was selected on the basis of their previously known humoral immune response to the YF vaccines. The selected children were categorized according to their YF-neutralizing antibody titers (PRNT) and referred to as seroconverters (PV-PRNT(+)) or nonseroconverters (PV-PRNT(-)). Following revaccination with the YF-17DD, the PV-PRNT(-) children (YF-17D-213/77 and YF-17DD groups) seroconverted and were referred as RV-PRNT(+). The cytokine-mediated immune response was investigated after short-term in vitro cultures of whole blood samples. The results are expressed as frequency of high cytokine producers, taking the global median of the cytokine index (YF-Ag/control) as the cut-off.
  
  
  RESULTS
  The YF-17D-213/77 and the YF-17DD substrains triggered a balanced overall inflammatory/regulatory cytokine pattern in PV-PRNT(+), with a slight predominance of IL-12 in YF-17DD vaccinees and a modest prevalence of IL-10 in YF-17D-213/77. Prominent frequency of neutrophil-derived TNF-α and neutrophils and monocyte-producing IL-12 were the major features of PV-PRNT(+) in the YF-17DD, whereas relevant inflammatory response, mediated by IL-12(+)CD8(+) T cells, was the hallmark of the YF-17D-213/77 vaccinees. Both substrains were able to elicit particular but relevant inflammatory events, regardless of the anti-YF PRNT antibody levels. PV-PRNT(-) children belonging to the YF-17DD arm presented gaps in the inflammatory cytokine signature, especially in terms of the innate immunity, whereas in the YF-17D-213/77 arm the most relevant gap was the deficiency of IL-12-producing CD8(+)T cells. Revaccination with YF-17DD prompted a balanced cytokine profile in YF-17DD nonresponders and a robust inflammatory profile in YF-17D-213/77 nonresponders.
  
  
  CONCLUSIONS
  Our findings demonstrated that, just like the YF-17DD reference vaccine, the YF-17D-213/77 seed lot induced a mixed pattern of inflammatory and regulatory cytokines, supporting its universal use for immunization.
authors.affiliation: Laboratório de Biomarcadores de Diagnóstico e Monitoração, Centro de Pesquisas René Rachou, FIOCRUZ, Belo Horizonte, Minas Gerais, Brasil.
authors.forename: Ana Carolina
authors.initials: AC
authors.lastname: Campi-Azevedo
authors.forename: Luiza Pacheco
authors.initials: LP
authors.lastname: de Araújo-Porto
authors.forename: Maria
authors.initials: M
authors.lastname: Luiza-Silva
authors.forename: Maurício Azevedo
authors.initials: MA
authors.lastname: Batista
authors.forename: Marina Angela
authors.initials: MA
authors.lastname: Martins
authors.forename: Renato
authors.initials: R
authors.lastname: Sathler-Avelar
authors.forename: Denise
authors.initials: D
authors.lastname: da Silveira-Lemos
authors.forename: Luiz Antonio Bastos
authors.initials: LA
authors.lastname: Camacho
authors.forename: Reinaldo
authors.initials: R
authors.lastname: de Menezes Martins
authors.forename: Maria
authors.initials: M
authors.lastname: de Lourdes de Sousa Maia
authors.forename: Roberto Henrique Guedes
authors.initials: RH
authors.lastname: Farias
authors.forename: Marcos
authors.initials: M
authors.lastname: da Silva Freire
authors.forename: Ricardo
authors.initials: R
authors.lastname: Galler
authors.forename: Akira
authors.initials: A
authors.lastname: Homma
authors.forename: José Geraldo Leite
authors.initials: JG
authors.lastname: Ribeiro
authors.forename: Jandira Aparecida Campos
authors.initials: JA
authors.lastname: Lemos
authors.forename: Maria
authors.initials: M
authors.lastname: Auxiliadora-Martins
authors.forename: Iramaya Rodrigues
authors.initials: IR
authors.lastname: Caldas
authors.forename: Silvana Maria
authors.initials: SM
authors.lastname: Elói-Santos
authors.forename: Andréa
authors.initials: A
authors.lastname: Teixeira-Carvalho
authors.forename: Olindo Assis
authors.initials: OA
authors.lastname: Martins-Filho
mesh_terms: D000914:Antibodies, Viral / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000097:blood*; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D015004:Yellow Fever / Q000097:blood / Q000276:immunology / Q000517:prevention & control*; D022341:Yellow Fever Vaccine / Q000276:immunology*; D015005:Yellow fever virus / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D016207:Cytokines; D022341:Yellow Fever Vaccine