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

Abstract

Fifteen million people each year receive post-exposure prophylaxis (PEP) to prevent rabies, yet the disease remains neglected and highly under-reported. Areas covered: In this systematic literature review, we assessed the immunogenicity, efficacy, and safety of a purified chick embryo cell-culture rabies vaccine (PCECV) for PEP against rabies by intramuscular (IM) or intradermal (ID) administration. We performed meta-analyses to compare immunogenicity according to the route of vaccine administration, study population, and PEP regimen, such as number of doses, and concomitant rabies immunoglobulin. Expert commentary: There were 54 estimates of immune responses to vaccination, which showed that in the overall population, after starting PEP with PCECV by the IM or ID route (≥2.5 IU per dose), almost all individuals had rabies virus neutralizing antibody (RVNA) titers above the World Health Organization (WHO) recommended serological threshold for an adequate immune response to vaccination (RVNA ≥0.5 IU/ml by day 14). In the overall population, PCECV had an acceptable safety profile. However, given that there are 59,000 human rabies deaths reported annually, the challenge is to improve access to PCECV for PEP against human rabies.

The Route of Administration of Rabies Vaccines: Comparing the Data

“…These initial two efficacy studies provided the proof needed that ID PEP was as effective as IM PEP when administered according to the schedules listed above and have served as models for designing additional clinical trials evaluating the effectiveness of new PEP regimens. Further clinical studies have confirmed that the other WHO prequalified rabies vaccines were also safe and effective for both IM PEP and ID PEP [ 10 , 13 , 24 , 32 , 33 , 34 , 35 , 36 ].…”

Immunogenicity and Safety of a Purified Vero Rabies Vaccine—Serum Free, Compared With 2 Licensed Vaccines, in a Simulated Rabies Post-Exposure Regimen in Healthy Adults in France: A Randomized, Controlled, Phase 3 Trial

“…In our study, nearly all participants reported complete neutralization (ACIP criteria at the time of study preparation) at all time points post-vaccination. However, comparisons with earlier clinical studies of rabies vaccines are difficult due to a trend toward slightly decreased RVNA titers observed in recent studies for licensed rabies vaccines [ 34 ]. The reasons for the observed lower RVNA titers in more recent studies are likely multifactorial and may include varying definitions of the neutralization or seroconversion thresholds, HRIG interference, and variability of the RFFIT among different laboratories due to lack of standardization or differences in references used.…”

Metabolomics profiling reveals differences in proliferation between tumorigenic and non-tumorigenic Madin-Darby canine kidney (MDCK) cells

“…Vaccination is the most effective and cost-efficient way to prevent the transmission of the virus. In addition to the traditional chicken embryo culture method for vaccine production, cell culture techniques are increasingly being employed, such as Vero cells for the production of COVID-19 vaccines ( Zhang et al, 2022 ), purified chick embryo cell-culture for rabies vaccines (PCECV; Preiss et al, 2018 ), and PER.C6 cells for the production of poliovirus vaccines ( Sanders et al, 2013 ).…”