Immunogenicity and Safety of Berna-Yf Compared With Two Other 17d Yellow Fever Vaccines in a Phase 3 Clinical Trial

Abstract

BERNA-YF (Flavimun) is a live, attenuated yellow fever (YF) vaccine of the 17D strain produced by Berna Biotech Ltd. following a transfer of technology from the Robert Koch Institute (RKI) in Berlin, Germany. In this phase 3 bridging study, the immunogenicity and safety of BERNA-YF were compared with the original RKI YF vaccine (RKI-YF) and to a current, commercially available YF vaccine, Stamaril (AP-YF; Aventis Pasteur, Lyon, France), in 304 healthy, adult volunteers. All three vaccines elicited an effective immune response with seroprotection achieved in 100% of individuals in each vaccine group at a neutralizing antibody titer > or = 1:10. BERNA-YF was shown to be comparable to the other two vaccine products, and subgroup analysis showed no differences in immune response between three consecutive production batches. The immune response to BERNA-YF and RKI-YF was very similar, with no significant difference in antibody titer between the two groups (P = 0.4634). However, AP-YF vaccination resulted in a significantly lower antibody titer (P < 0.0001 versus BERNA-YF). Males exhibited a higher antibody response than females to both BERNA-YF and RKI-YF, but not to AP-YF. All three vaccines were well tolerated and no serious adverse events were reported.

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).…”

Efficacy and Duration of Immunity after Yellow Fever Vaccination: Systematic Review on the Need for a Booster Every 10 Years

“…10,11,23 Protective immunity after YF vaccination. Twelve studies in 11 articles 6,10,[25][26][27][28][29][30][31][32][33] addressed the efficacy of YF vaccine in terms of immunogenicity (Table 3). Seroconversion rates were consistently 90% in 9 of 10 studies.…”

The phylogeny of yellow fever virus 17D vaccines

“…Further on, the vaccine strains produced by Crucell Switzerland AG [7] together with the former vaccine strain from the Robert Koch-Institute (RKI, Germany) and the strain YFV-17D-213 which is provided by the World Health Organization (WHO, Switzerland) [12,15] form a clade which is especially strongly supported in the Bayesian analysis (0.99pp, 69bs, 70bs). These two 17D subgroups are nested in a polytomy with the vaccine strain Stamaril ® (France), an isolate from a YEL-AVD from Spain after vaccination with Stamaril ® [16] and the Chinese vaccine strain YFV 17D-Tiantan.…”

“…In this work we sequenced the whole genome (10862 bp) of different passages of Crucell's YFV-17D strain, which was only sequenced partially until now [7]. This virus strain is used for vaccine production, but has not been licensed so far.…”