A comprehensive Phase 3 clinical trial conducted in China's Zhejiang Province has revealed superior immunogenicity results for rabies vaccine boosters administered following the Zagreb vaccination regimen compared to the traditional Essen protocol.
The randomized, open-label study, carried out between July 2021 and December 2022, evaluated 767 participants who received booster doses of the Speeda vaccine six months after their primary vaccination series. The trial specifically compared single versus double-dose boosters in both Zagreb and Essen regimen recipients.
Immunogenicity Findings
The study demonstrated remarkable antibody responses across all groups 14 days after booster administration. The Zagreb regimen groups achieved significantly higher geometric mean concentrations (GMCs) compared to Essen regimen groups, regardless of booster dose frequency. Groups receiving the Zagreb regimen showed GMCs of 48.80 IU/mL and 64.38 IU/mL for single and double boosters respectively, substantially exceeding the Essen regimen groups' values of 34.25 IU/mL and 42.89 IU/mL.
Notably, while two-dose boosters produced higher antibody levels than single doses, even the single-dose booster generated protective antibody levels well above the 0.5 IU/mL threshold. This finding suggests that a single booster may be sufficient for maintaining protection against rabies exposure.
Safety Profile Assessment
The safety analysis revealed slightly higher adverse reaction rates in Zagreb regimen recipients (11.22% and 15.79% for single and double boosters) compared to Essen regimen groups (3.68% and 10.87%). However, all reported reactions were mild and transient, typically resolving within three days post-vaccination.
Injection site pain emerged as the most common local reaction, with incidence rates ranging from 1.63% to 12.11% across groups. Systemic reactions were primarily limited to fever, affecting between 1.05% and 3.16% of participants. Importantly, no serious adverse events were reported throughout the study period.
Cost-Effectiveness Implications
The study's findings carry significant implications for global rabies prevention strategies, particularly in resource-limited settings. The demonstration that single-dose boosters can provide adequate protection offers a more economical approach to maintaining immunity against rabies, potentially improving vaccination program accessibility and compliance.
Long-term Immunity
At the six-month follow-up, all groups maintained 100% antibody positive rates, though titers had decreased from peak levels. The Zagreb regimen groups continued to show higher antibody levels compared to Essen regimen recipients, with GMCs ranging from 20.51 to 31.85 IU/mL versus 17.00 to 22.32 IU/mL.
Study Limitations
The researchers noted that the study was limited to evaluating booster responses at six months post-primary vaccination. Further research is needed to assess the effectiveness of boosters administered at different intervals, particularly given that some vaccines have shown strong immunogenicity even when boosted after longer periods.
