Reactogenicity of yellow fever vaccines in a randomized, placebo-controlled trial

Abstract

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.

Early molecular correlates of adverse events following yellow fever vaccination

“…No significant difference in age, body mass index, gender, and ethnicity were found between those with or without AEs (Table 1). Overall, our published AE rates were comparable to the previously reported AE rates following YFLAV administration (21%-72%), depending on the study design (11)(12)(13)(14)(15). Using the distribution of fever onset as a guide, as it has been shown to be a significant AE in those who received YFLAV compared with placebo (11), we divided the AEs into immediate or delayed based on whether the AE onset occurred before or after 24 hours after vaccination ( Figure 2, A-C).…”

Evaluation of two yellow fever vaccines for routine immunization programs in Argentina

“…Rates of 15 to 18% of vaccinees experiencing local reactions and approximately 30% reporting solicited systemic reactions were consistent with other published reports. [15][16][17] The overall occurrence of severe local and systemic adverse reactions in our study population, 2 to 2.5%, was very low. In addition, these rates of occurrence of severe adverse reactions further decreased in the cohort of subjects 60 years of age and older.…”

“…Normally, an excess risk of adverse events resulting from vaccination is most accurately estimated by comparison to a placebo, as reported recently in Brazil. 17 In that study, comparing the 17DD, 17D-213 and placebo, an excess of 3.5 to 7.4% for all adverse events was noted in vaccine recipients.…”

“…The other vaccine Vacina Contra Febre Amarela (VCFA), is produced by Bio-Manguinhos, Brazil, Both YF vaccines are highly immunogenic. 6,14 Safety and reactogenicity data are crucial in the acceptance and uptake of the vaccination program of YF. This study was initiated to evaluate the safety profiles of these two vaccines in an enzootic YF region, the northern province of Jujuy, Argentina.…”

“…Local reactions, such as erythema, swelling and pain at the injection site, occur in a minority of adult vaccinees and resolve within 5 to 7 days after immunisation. [14][15][16]24 Approximately 30% of all vaccinees experience mild systemic reactions, such as headache, myalgia, or low-grade fever for up to 10 days after vaccination. It is considered that some systemic reactions, such as fever, headache and myalgia may reflect a release of pro-inflammatory cytokines by dendritic cells.…”