title: Subdoses of 17DD yellow fever vaccine elicit equivalent virological/immunological kinetics timeline.
abstract: BACKGROUND
  The live attenuated 17DD Yellow Fever vaccine is one of the most successful prophylactic interventions for controlling disease expansion ever designed and utilized in larger scale. However, increase on worldwide vaccine demands and manufacturing restrictions urge for more detailed dose sparing studies. The establishment of complementary biomarkers in addition to PRNT and Viremia could support a secure decision-making regarding the use of 17DD YF vaccine subdoses. The present work aimed at comparing the serum chemokine and cytokine kinetics triggered by five subdoses of 17DD YF Vaccine.
  
  
  METHODS
  Neutralizing antibody titers, viremia, cytokines and chemokines were tested on blood samples obtained from eligible primary vaccinees.
  
  
  CONCLUSIONS
  The results demonstrated that a fifty-fold lower dose of 17DD-YF vaccine (587 IU) is able to trigger similar immunogenicity, as evidenced by significant titers of anti-YF PRNT. However, only subdoses as low as 3,013 IU elicit viremia kinetics with an early peak at five days after primary vaccination equivalent to the current dose (27,476 IU), while other subdoses show a distinct, lower in magnitude and later peak at day 6 post-vaccination. Although the subdose of 587 IU is able to trigger equivalent kinetics of IL-8/CXCL-8 and MCP-1/CCL-2, only the subdose of 3,013 IU is able to trigger similar kinetics of MIG/CXCL-9, pro-inflammatory (TNF, IFN-γ and IL-2) and modulatory cytokines (IL-5 and IL-10).
  
  
  CONCLUSIONS
  The analysis of serum biomarkers IFN-γ and IL-10, in association to PRNT and viremia, support the recommendation of use of a ten-fold lower subdose (3,013 IU) of 17DD-YF vaccine.
authors.affiliation: Centro de Pesquisas René Rachou - Fiocruz, Belo Horizonte, Minas Gerais, Brazil. accampi@cpqrr.fiocruz.br.
authors.forename: Ana Carolina
authors.initials: AC
authors.lastname: Campi-Azevedo
authors.forename: Paula
authors.initials: P
authors.lastname: de Almeida Estevam
authors.forename: Jordana Grazziela
authors.initials: JG
authors.lastname: Coelho-Dos-Reis
authors.forename: Vanessa
authors.initials: V
authors.lastname: Peruhype-Magalhães
authors.forename: Gabriela
authors.initials: G
authors.lastname: Villela-Rezende
authors.forename: Patrícia Flávia
authors.initials: PF
authors.lastname: Quaresma
authors.forename: Maria de Lourdes Sousa
authors.initials: Mde L
authors.lastname: Maia
authors.forename: Roberto Henrique Guedes
authors.initials: RH
authors.lastname: Farias
authors.forename: Luiz Antonio Bastos
authors.initials: LA
authors.lastname: Camacho
authors.forename: Marcos da Silva
authors.initials: Mda S
authors.lastname: Freire
authors.forename: Ricardo
authors.initials: R
authors.lastname: Galler
authors.forename: Anna Maya Yoshida
authors.initials: AM
authors.lastname: Yamamura
authors.forename: Luiz Fernando Carvalho
authors.initials: LF
authors.lastname: Almeida
authors.forename: Sheila Maria Barbosa
authors.initials: SM
authors.lastname: Lima
authors.forename: Rita Maria Ribeiro
authors.initials: RM
authors.lastname: Nogueira
authors.forename: Gloria Regina
authors.initials: GR
authors.lastname: Silva Sá
authors.forename: Darcy Akemi
authors.initials: DA
authors.lastname: Hokama
authors.forename: Ricardo
authors.initials: R
authors.lastname: de Carvalho
authors.forename: Ricardo Aguiar Villanova
authors.initials: RA
authors.lastname: Freire
authors.forename: Edson Pereira
authors.initials: EP
authors.lastname: Filho
authors.forename: Maria da Luz Fernandes
authors.initials: Mda L
authors.lastname: Leal
authors.forename: Akira
authors.initials: A
authors.lastname: Homma
authors.forename: Andréa
authors.initials: A
authors.lastname: Teixeira-Carvalho
authors.forename: Reinaldo Menezes
authors.initials: RM
authors.lastname: Martins
authors.forename: Olindo Assis
authors.initials: OA
authors.lastname: Martins-Filho
mesh_terms: D000293:Adolescent; D000328:Adult; D057134:Antibodies, Neutralizing / Q000097:blood*; D000914:Antibodies, Viral / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D016207:Cytokines / Q000097:blood; D004306:Dose-Response Relationship, Immunologic; D005434:Flow Cytometry; D006801:Humans; D007700:Kinetics; D008297:Male; D014611:Vaccination / Q000379:methods; D014613:Vaccines, Attenuated / Q000008:administration & dosage; D014766:Viremia / Q000097:blood; D015004:Yellow Fever / Q000517:prevention & control*; D022341:Yellow Fever Vaccine / Q000008:administration & dosage*; D055815:Young Adult
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D015415:Biomarkers; D016207:Cytokines; D014613:Vaccines, Attenuated; D022341:Yellow Fever Vaccine