Reactogenicity of yellow fever vaccines in a randomized, placebo-controlled trial.
OBJECTIVE
To compare the reactogenicity of three yellow fever (YF) vaccines from WHO-17D and Brazilian 17DD substrains (different seed-lots) and placebo.


METHODS
The study involved 1,087 adults eligible for YF vaccine in Rio de Janeiro, Brazil. Vaccines produced by Bio-Manguinhos, Fiocruz (Rio de Janeiro, Brazil) were administered ("day 0") following standardized procedures adapted to allow blinding and blocked randomization of participants to coded vaccine types. Adverse events after immunization were ascertained in an interview and in diary forms filled in by each participant. Liver enzymes were measured on days 0, 4-20 and 30 of the study. Viremia levels were measured on days 4 to 20 of follow-up. The immune response was verified through serologic tests.


RESULTS
Participants were mostly young males. The seroconversion rate was above 98% among those seronegative before immunization. Compared to placebo, the excess risk of any local adverse events ranged from 0.9% to 2.5%, whereas for any systemic adverse events it ranged from 3.5% to 7.4% across vaccine groups. The excess risk of events leading to search for medical care or to interruption of work activities ranged from 2% to 4.5%. Viremia was detected in 3%-6% of vaccinees up to 10 days after vaccination. Variations in liver enzyme levels after vaccination were similar in placebo and vaccine recipients.


CONCLUSIONS
The frequency of adverse events post-immunization against YF, accounting for the background occurrence of nonspecific signs and symptoms, was shown for the first time to be similar for vaccines from 17D and 17DD substrains. The data also provided evidence against viscerotropism of vaccine virus.
Escola Nacional de Saúde Pública, Fiocruz, Rio de Janeiro, RJ, Brasil.
Luiz Antonio Bastos
LA
Camacho
Savitri Gomes
SG
de Aguiar
Marcos da Silva
Mda S
Freire
Maria da Luz Fernandes
Mda L
Leal
Jussara Pereira
JP
do Nascimento
Takumi
T
Iguchi
José Azevedo
JA
Lozana
Roberto Henrique Guedes
RH
Farias
D000328:Adult; D000410:Alanine Transaminase / Q000032:analysis; D000914:Antibodies, Viral / Q000276:immunology*; D001219:Aspartate Aminotransferases / Q000032:analysis; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008099:Liver / Q000201:enzymology; D008297:Male; D014766:Viremia / Q000097:blood / Q000276:immunology; D015004:Yellow Fever / Q000276:immunology / Q000517:prevention & control*; D022341:Yellow Fever Vaccine / Q000009:adverse effects / Q000276:immunology*; D015005:Yellow fever virus / Q000276:immunology*
D000914:Antibodies, Viral; D022341:Yellow Fever Vaccine; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase