17DD yellow fever vaccine: a double blind, randomized clinical trial of immunogenicity and safety on a dose-response study

Reinaldo M Martins, Maria de Lourdes S Maia, Roberto Henrique G Farias, Luiz Antonio B Camacho, Marcos S Freire, Ricardo Galler, Anna Maya Yoshida Yamamura, Luiz Fernando C Almeida, Sheila Maria B Lima, Rita Maria R Nogueira, Gloria Regina S Sá, Darcy A Hokama, Ricardo de Carvalho, Ricardo Aguiar V Freire, Edson Pereira Filho, Maria da Luz Fernandes Leal, Akira Homma, Reinaldo M Martins, Maria de Lourdes S Maia, Roberto Henrique G Farias, Luiz Antonio B Camacho, Marcos S Freire, Ricardo Galler, Anna Maya Yoshida Yamamura, Luiz Fernando C Almeida, Sheila Maria B Lima, Rita Maria R Nogueira, Gloria Regina S Sá, Darcy A Hokama, Ricardo de Carvalho, Ricardo Aguiar V Freire, Edson Pereira Filho, Maria da Luz Fernandes Leal, Akira Homma

Abstract

Objective: To verify if the Bio-Manguinhos 17DD yellow fever vaccine (17DD-YFV) used in lower doses is as immunogenic and safe as the current formulation.

Results: Doses from 27,476 IU to 587 IU induced similar seroconversion rates and neutralizing antibodies geometric mean titers (GMTs). Immunity of those who seroconverted to YF was maintained for 10 mo. Reactogenicity was low for all groups.

Methods: Young and healthy adult males (n = 900) were recruited and randomized into 6 groups, to receive de-escalating doses of 17DD-YFV, from 27,476 IU to 31 IU. Blood samples were collected before vaccination (for neutralization tests to yellow fever, serology for dengue and clinical chemistry), 3 to 7 d after vaccination (for viremia and clinical chemistry) and 30 d after vaccination (for new yellow fever serology and clinical chemistry). Adverse events diaries were filled out by volunteers during 10 d after vaccination. Volunteers were retested for yellow fever and dengue antibodies 10 mo later. Seropositivity for dengue was found in 87.6% of volunteers before vaccination, but this had no significant influence on conclusions.

Conclusion: In young healthy adults Bio-Manguinhos/Fiocruz yellow fever vaccine can be used in much lower doses than usual. INTERNATIONAL REGISTER: ISRCTN 38082350.

Keywords: Bio-Manguinhos/Fiocruz; dengue interactions; dose-response study; immunogenicity; reactogenicity; safety; viremia; yellow fever vaccine.

Figures

https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3903908/bin/hvi-9-879-g1.jpg
Figure 1. Study population.
https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3903908/bin/hvi-9-879-g2.jpg
Figure 2. Reverse cumulative distribution of neutralizing antibodies titers per group.
https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3903908/bin/hvi-9-879-g3.jpg
Figure 3. Clinical adverse events, by group, IU/dose.
https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3903908/bin/hvi-9-879-g4.jpg
Figure 4. Number of viral RNA copies by day after vaccination.

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