Comparative Immunogenicity and Safety Trial of 2 Different Schedules of Single-visit Intradermal Rabies Postexposure Vaccination

Abstract

Background Effective and safe single-visit rabies vaccination for pre- and postexposure prophylaxis (PrEP and PEP) could substantially simplify rabies prevention and therefore increase compliance. Methods In a comparative trial, 303 healthy adults received a primary vaccination that consisted of 2 intradermal (ID) doses of 0.1 mL of the purified chicken embryo cell vaccine (PCEV) during a single visit. One year later, participants were randomly assigned to receive either 4 or 2 ID PEP booster doses of 0.1 mL PCEV during a single visit. The primary endpoint for immunogenicity was the percentage of participants with an adequate antibody level (>0.5 IU/mL) 7 days after the booster doses. The safety endpoint was the proportion of participants who developed adverse events (AEs) following primary and/or booster vaccination. Results All participants, except 1 (99.3%) in each study group, had a rabies antibody titer >0.5 IU/mL on day 7 following the booster schedules. Participants exposed to the 4-dose PEP schedule had a geometric mean titer of 20 IU/mL vs 14 IU/mL for the 2-dose PEP schedule (P = .0228). Local reactions at the injection site following PrEP and PEP were mild and transient and only seen in 14.9% and 49.6%–53% of the participants, respectively. No serious AEs were reported. Conclusions In healthy adults, a 2-dose (2 × 0.1 mL) single-visit ID PEP schedule was as immunologically adequate and safe as a 4-dose (4 × 0.1 mL) single-visit PEP schedule 7 to 28 months following a 2-dose (2 × 0.1 mL) single-visit ID PREP. Clinical Trials Registration EudraCT 2014-00183612.

Safety and immunogenicity of a simian-adenovirus-vectored rabies vaccine: an open-label, non-randomised, dose-escalation, first-in-human, single-centre, phase 1 clinical trial

“…2 This recommendation is based on studies that have mostly evaluated single-visit multisite intradermal vaccination. 16,26,27 These studies have tended to show that most, but not all, participants attain virus neutralising antibody titres of more than 0•5 IU/mL after vaccination (with median virus neutralising antibody titres <10 IU/mL at day 14-35), followed by waning of virus neutralising antibody titres to a median of less than 0•5 IU/mL 1-2 years later. These previous data suggest clear room for improvement in the immunogenicity of single-visit vaccination, and results in the current study appear favourably comparable.…”

“…Similar to those studies, we considered virus neutralising antibody titres of 0•5 IU/mL or more 7 days after initiation of simulated PEP to be the key indicator of an adequate response (the anamnestic response to PEP would be especially important in any previously vaccinated individuals in whom virus neutralising antibody titres were less than 0•5 IU/mL at day 365). 15,16 We considered the attainment of this threshold 7 days after a single dose to be a more stringent goal than attainment of a similar response with a WHO-recommended PEP regimen including a second dose at day 3. The regimen of single-site intramuscular administration on days 0, 7, and 21 was selected to maximise volunteer benefit from participation in this phase of the study, independent of the immunogenicity of ChAdOx2 RabG, as it is a UK-recommended PrEP regimen (unlike any WHO-recommended regimen for PEP in previously vaccinated individuals).…”

Vaccines and Senior Travellers

“…Therefore, promoting pre-exposure prophylaxis is a key preventive strategy for avoiding the risk of rabies, especially during travel to endemic areas. Rabies pre-exposure prophylaxis (PrEP) greatly simplifies PEP, by obviating the need for HRIG, and by reducing the number of PEP vaccine doses required ( Soentjens et al, 2019b ).…”

Vaccinating children in high-endemic rabies regions: what are we waiting for?

“…Recent trials suggest that a simulated PEP booster-delayed for years-in combination with a 2²ID or 1²ID PrEP will improve the anamnestic responses after the booster. 4 Hence, instead of three vaccinations in 1 week (3 2 ID PEP), the 2²ID PrEP schedule, followed by a 1 4 ID PEP in case of exposure, can improve feasibility in endemic LMICs due to longer time intervals (figure 1: schedule 1.B, 1.C, 1.D). Countries can also consider a double-dose schedule at three different visits, using the 3 2 ID PEP vaccinations in a PrEP schedule, which would fit in the EPI programme: at the age of 9-12 months, and at the age of 6 and 12 years ( figure 1: schedule 3).…”