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

被引:67
作者
Campi-Azevedo, Ana Carolina [1 ]
Estevam, Paula de Almeida [1 ]
Coelho-dos-Reis, Jordana Grazziela [1 ]
Peruhype-Magalhaes, Vanessa [1 ]
Villela-Rezende, Gabriela [1 ]
Quaresma, Patricia Flavia [1 ]
Sousa Maia, Maria de Lourdes [2 ]
Guedes Farias, Roberto Henrique [2 ]
Bastos Camacho, Luiz Antonio [3 ]
Freire, Marcos da Silva [2 ]
Galler, Ricardo [2 ]
Yoshida Yamamura, Anna Maya [2 ]
Carvalho Almeida, Luiz Fernando [2 ]
Barbosa Lima, Sheila Maria [2 ]
Ribeiro Nogueira, Rita Maria [4 ]
Silva Sa, Gloria Regina [2 ]
Hokama, Darcy Akemi [2 ]
de Carvalho, Ricardo [2 ]
Villanova Freire, Ricardo Aguiar [5 ]
Pereira Filho, Edson [5 ]
Fernandes Leal, Maria da Luz [2 ]
Homma, Akira [2 ]
Teixeira-Carvalho, Andrea [1 ]
Martins, Reinaldo Menezes [2 ]
Martins-Filho, Olindo Assis [1 ,2 ]
机构
[1] Fiocruz MS, Ctr Pesquisas Rene Rachou, Belo Horizonte, MG, Brazil
[2] Fiocruz MS, BR-21045900 Rio De Janeiro, Brazil
[3] Fiocruz MS, Escola Nacl Saude Publ, BR-21045900 Rio De Janeiro, Brazil
[4] Fiocruz MS, Inst Oswaldo Cruz, BR-21045900 Rio De Janeiro, Brazil
[5] Inst Biol Exercito, Rio De Janeiro, Brazil
关键词
Yellow fever; Vaccine; Dose-response; Viremia; Cytokines; Ckemokines; ADAPTIVE IMMUNITY; PCR ASSAYS; CULTURE; INNATE;
D O I
10.1186/1471-2334-14-391
中图分类号
R51 [传染病];
学科分类号
100201 [内科学];
摘要
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-gamma and IL-2) and modulatory cytokines (IL-5 and IL-10). Conclusions: The analysis of serum biomarkers IFN-gamma 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.
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页数:12
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