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

Abstract

(2015) 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 , Human Vaccines & Immunotherapeutics, 11:2, 435-442, DOI: 10.4161/21645515.2014 The aim of this Phase IIIb, open-label, randomized study was to demonstrate the non-inferiority of immune responses and to assess the safety of a purified chick-embryo cell rabies vaccine (PCECV) in healthy Chinese children (6 to 17 years) and older adults (51 years) following 2 alternative intramuscular (IM) simulated post-exposure prophylaxis (PEP) regimens: 4-dose Zagreb or 5-dose Essen regimen. Serum samples were collected prior to vaccination on Days 1 and 15 and on day 43 to assess immune response by rabies virus neutralizing antibody (RVNA) concentrations. Solicited adverse events (AEs) were recorded for up to 7 days following each vaccine dose, and unsolicited AEs throughout the entire study period. PCECV vaccination induced a strong immune response at Day 15, and the non-inferiority in immune response of the Zagreb vs. the Essen regimen was demonstrated in children and older adults. At Day 15,100% of children (N D 224), and 99% of subjects 51 years of age (N D 376) developed adequate RVNA concentrations (0.5 IU/mL); at Day 43 all subjects achieved RVNA concentrations 0.5 IU/mL, for both PEP regimens. The well-known tolerability and safety profile of the PCECV was again observed in this study following either Zagreb or Essen regimens. Rabies PEP vaccination with PCECV following a Zagreb regimen induced immune responses non-inferior to those of the Essen regimen, and had a similar safety and tolerability profile to the Essen regimen in Chinese children, adolescents, and adults over 51 years. ClinicalTrials.gov identifier: NCT01680016.

Post-exposure prophylaxis (PEP) for rabies with purified chick embryo cell vaccine: a systematic literature review and meta-analysis

“…Mild to moderate solicited local and systemic reactions, with pain being the most reported solicited local AE (38% and 40% of children following the Zagreb and Essen regimens, respectively) and fatigue as the most common systemic AE (15% and 13% of children after the Zagreb and Essen regimens respectively), were reported in a study on healthy children [25].…”

“…A second study conducted among a subgroup of healthy children aged 1-5 years reported a GMT of 12.0 IU/mL on D14 and 13.0 IU/mL on D42 for the IM Zagreb regimen (2-1-1). For the Essen regimen (1-1-1-1-1) a GMT of 14.0 IU/mL was reported on D14 and 24.0 IU/mL on D42 [25]. For both regimens at Day 14, the seroconversion rate was 100% (95% CI: 97-100).…”

“…We identified 10 studies reporting data in children aged 1-17 years [10,19,25,29,31,40,53,54,56,61]. At Day 14, all children had Day 14 RVNA titers ≥0.5 IU/mL, but not all studies reported seroconversion rates.…”

“…Unsolicited AEs were noted in 3% (Zagreb regimen) and 8% (Essen regimen) of children, with upper respiratory tract infection being the most frequent, regardless of regimen. No SAEs were reported [25]. A study conducted among bite cases reported fever mostly in children aged <5 years; no further information on safety of the vaccine could be retrieved from the manuscript [48].…”

“…The review identified 48 reports of reactogenicity and safety of PCECV, including four studies that assessed children or pregnant women [25,48,49,54]. The most frequently reported systemic AEs were myalgia, headache, fever, or having a feverish feeling, and overall, our descriptive analysis indicated that adverse reactions including headache, erythema, induration, and lymphadenopathy may be more often reported among individuals receiving PCECV by ID than IM administration.…”