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Open Access Highly Accessed Research article

Subdoses of 17DD yellow fever vaccine elicit equivalent virological/immunological kinetics timeline

Ana Carolina Campi-Azevedo1*, Paula de Almeida Estevam1, Jordana Grazziela Coelho-dos-Reis1, Vanessa Peruhype-Magalhães1, Gabriela Villela-Rezende1, Patrícia Flávia Quaresma1, Maria de Lourdes Sousa Maia2, Roberto Henrique Guedes Farias2, Luiz Antonio Bastos Camacho3, Marcos da Silva Freire2, Ricardo Galler2, Anna Maya Yoshida Yamamura2, Luiz Fernando Carvalho Almeida2, Sheila Maria Barbosa Lima2, Rita Maria Ribeiro Nogueira4, Gloria Regina Silva Sá2, Darcy Akemi Hokama2, Ricardo de Carvalho2, Ricardo Aguiar Villanova Freire5, Edson Pereira Filho5, Maria da Luz Fernandes Leal2, Akira Homma2, Andréa Teixeira-Carvalho1, Reinaldo Menezes Martins2 and Olindo Assis Martins-Filho1

Author Affiliations

1 Centro de Pesquisas René Rachou – Fiocruz, Belo Horizonte, Minas Gerais, Brazil

2 Bio-Manguinhos, Fiocruz, Rio de Janeiro, Brazil

3 Escola Nacional de Saúde Pública, Fiocruz, Rio de Janeiro, Brazil

4 Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, Brazil

5 Instituto de Biologia do Exército, Rio de Janeiro, Brazil

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BMC Infectious Diseases 2014, 14:391  doi:10.1186/1471-2334-14-391

Published: 15 July 2014

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.

Results and discussion

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.

Keywords:
Yellow fever; Vaccine; Dose–response; Viremia; Cytokines; Ckemokines