Comparison of safety and immunogenicity of purified chick embryo cell vaccine using Zagreb and Essen regimens in patients with category II exposure in China

Abstract

The aim was to compare the safety and immunogenicity of purified chick embryo cell vaccine (PCECV) with Zagreb 2-1-1 and Essen 1-1-1-1-1 regimens in patients with WHO category II exposure in China. Side effects including systemic and local symptoms were recorded for all patients during vaccination with purified chick embryo cell vaccine (PCECV) under Zagreb 2-1-1 or Essen 1-1-1-1-1 regimens, and the rabies neutralization antibody titers in patients' serum at days 0, 7, 14, 45, 365 post-immunization were measured to determine the immunogenicity. Fever and pain were the most common events for systemic and local symptoms respectively, and most side effects (86.78%, 105/121) occurred after the first dose of vaccination. Safety analysis showed differences in side effects in<5-year-old patients between Zagreb and Essen regimens, especially after the first dose of vaccination (P = 0.043). Immunogenicity analysis indicated that Zagreb can achieve higher neutralization antibody titers and a greater seroconversion rate in a shorter time but had less persistence than Essen. When compared with the Essen regimen, the Zagreb regimen had a different immunogenicity in all study subjects, and different safety profile in young children, and a further study with a larger population and longer surveillance is warranted.

Rabies post-exposure prophylaxis for a child with severe allergic reaction to rabies vaccine

“…However, safety was more important than immunogenicity for the clinical vaccination, especially for this child with allergy history and under Zagreb regimen, as we previously found that most adverse events (AEs) occurred in <5-year children and Zagreb showed more AEs than Essen after first dose of vaccination. 2 More importantly, we can't absolutely certain the allergic reaction was caused solely by animal-sourced gelatin. Thus, it should be very careful to monitor the safety during the immunization.…”

“…RVNA titers in serum were measured under masked conditions using a rapid fluorescent focus inhibition test (RFFIT). 2,3 Reference data was adapted from the mean RVNA titers of local < 5-year-old children under Zagreb regimen in our previous study 3 In summary, the treatment of this case with severe allergic reaction to PVRV was very difficult and complex. It is lucky that, unlike many countries else in the world, China has multiple types of rabies vaccines (ex.…”

“…Timely and proper use of modern rabies vaccines and immunoglobulins is a crucial method to prevent rabies virus infection post-exposure. Although rabies vaccines in the market had been carefully evaluated, both local adverse events (AEs) and systemic AEs were normally reported during the immunization process 2,3 and mild systemic reactions had been reported in up to 40% of recipients. 4 However, severe adverse events that had to stop or change the immunization program were rarely reported.…”

Immunogenicity and safety of purified chick-embryo cell rabies vaccine under Zagreb 2-1-1 or 5-dose Essen regimen in Chinese children 6 to 17 years old and adults over 50 years: A randomized open-label study

“…[9][10][11] Clinical trials conducted with purified chick-embryo cell vaccines (PCECV) have consistently reported that protective virusneutralizing antibodies (RVNA) are usually induced by Day 14 following first vaccine dose, and the immunogenicity/efficacy and safety profiles of the vaccine have been well established in children and adults in previously simulated PEP studies involving healthy subjects or post exposure studies in subjects exposed to suspected or confirmed rabid animals. [12][13][14][15][16][17][18][19] Moreover, a study assessing the anamnestic response following a single booster dose administered 2 years after a primary 3-dose immunization with PCECV indicated that it was potentially able to elicit long-lasting immune responses even after 14 years. 20 In China, where 12-15 million doses of rabies vaccine are estimated to be administered annually, 7,21,22 the traditional 5-dose Essen regimen recommended by the WHO has been widely adopted since years, 23 while the Zagreb regimen has been only recently approved for PCECV preparations.…”

Zagreb Regimen, an Abbreviated Intramuscular Schedule for Rabies Vaccination

“…Studies of adverse local or systemic reactions conducted in China on healthy volunteers and exposed subjects did not detect any significant differences between the Essen and Zagreb regimens (18)(19)(20)(21)(22)27). However, Huang et al (28) reported that the rate of adverse reactions to Zagreb was higher than that for Essen (2.37% versus 1.75%).…”