Immunogenicity, safety and antibody persistence of a purified vero cell cultured rabies vaccine (Speeda) administered by the Zagreb regimen or Essen regimen in post-exposure subjects

Abstract

Aim: To compare the safety, immunogenicity and long-term effect of a purified vero cell cultured rabies vaccine in post-exposure subjects following 2 intramuscular regimens, Zagreb or Essen regimen.

Methods: Serum samples were collected before vaccination and on days 7, 14, 42, 180 and 365 post vaccination. Solicited adverse events were recorded for 7 d following each vaccine dose, and unsolicited adverse events throughout the entire study period. This study was registered with ClinicalTrials.gov (NCT01821911 and NCT01827917).

Results: No serious adverse events were reported. Although Zagreb regimen had a higher incidence of adverse reactions than Essen regimen at the first and second injection, the incidence was similar at the third and fourth injection between these 2 groups as well. At day 42, 100% subjects developed adequate rabies virus neutralizing antibody concentrations (≥ 0.5IU/ml) for both regimens. At days 180 and 365, the antibody level decreased dramatically, however, the percentage of subjects with adequate antibody concentrations still remained high (above 75% and 50% respectively). None of confirmed rabies virus exposured subjects had rabies one year later, and percentage of subjects with adequate antibody concentrations reached 100% at days 14 and 42.

Conclusions: Rabies post-exposure prophylaxis vaccination with PVRV following a Zagreb regimen had a similar safety, immunogenicity and long-term effect to the Essen regimen in China.

Keywords: Immunogenicity; Post-exposure; Protective effect; Rabies vaccine; Safety.

Figures

Figure 1.

Flow chart of immunogenicity and safety of the vaccine in participants throughout the trial.

Figure 2.

Percentage of subjects with RVNA concentrations ≥ 0.5IU/ml of the vaccine on days 7, 14, 42, 180, 365. Percentage of rate difference was 24.3%, 95%CI: 26.5 to 112.5 on day 7.

Figure 3.

Rabies virus neutralizing antibody concentrations (GMC) in the Zagreb and Essen regimens on days 7, 14, 42, 180, 365. Error bars and values in parenthesis represent 95% CI.

Figure 4.

Rabies virus neutralizing antibody concentrations (GMC) of patients exposed to laboratory-proven rabies infected dogs in the Zagreb regimen on days 7,14 and 42. Error bars and values in parenthesis represent 95% CI. Y-axis is logarithmic scale of GMC.

Figure 5.

Percentage of subjects exposed to laboratory-proven rabies infected dogs with RVNA concentrations ≥ 0.5IU/ml in the Zagreb regimen on days 7, 14 and 42. 95% CI on day 7 is 8.4 to 41.0, while on days 14 and 42 is 100 to 100.