Hoe goed herinnert het afweersysteem een inenting tegen hondsdolheid vijf jaar na een enkele injectie?

Rationale: The main purpose of prophylactic rabies pre-exposure immunization (PrEP) is to induce an effective and rapid anamnestic antibody response after revaccination that obviates the need for human rabies immunoglobulins (RIG) and simplifies post-exposure immunization (PEP) to just 2 doses of rabies vaccine (D1, D4) in case of high-risk bite wounds. Many travellers decline pre-travel PrEP because of costs and insufficient time between visit at the travel clinic and departure. If a single dose of rabies vaccine would be equally effective in inducing a rapid and adequate anamnestic antibody response, guidelines on pre-travel PrEP could be simplified. In particular, the induction of long-term immunological memory might be an issue in the case of single-visit PrEP. To evaluate if single-visit PrEP is a reasonable alternative for one of the approved current standards, three-visit PrEP, we aim to study whether single-visit priming results in non-inferior long-term immunological memory, that is boostable by simulated post-exposure prophylaxis (PEP) after five years. Objective: The aim of this study is to demonstrate that a single dose of rabies vaccine can induce an equally rapid and adequate anamnestic antibody response as 3-dose PrEP to revaccination five years later. Study design: Randomized controlled non-inferiority trial. Study population: Healthy adult volunteers. Intervention: Participants will be randomized between standard 3-dose intramuscular PrEP (D1, D8, D22) or single-dose PrEP (standard intramuscular dose). After 5 years, all subjects will receive a simulated 2-dose post-exposure intramuscular vaccination schedule (D1 and D4). Serum (all participants) and blood samples (50 participants) are collected after PrEP at D1, D57/D78 (depending on study group), year 1, year 2 and year 5; and at D1, D8 and D15 after simulated PEP vaccination. Main study parameters/endpoints: The primary endpoint is the rate of increase of geometric mean concentrations (GMC) of neutralizing antibodies between day 1 and day 8 after revaccination. Nature and extent of the burden and risks associated with participation, benefit and group relatedness: In total, 3 or 5 injections will be given with a registered rabies vaccine. A maximum of 98 mL of blood will be collected during 7 sampling moments. Depending on the study arm eight to ten visits are required for the study. Participants are asked to complete a diary for safety evaluation during the study. The standard 3-dose PrEP (D1, D8, D22) has been endorsed by the WHO. No risks are associated with participation in this study other than those of routine vaccination and minimal to moderate physical discomfort that can be experienced after vaccination or the collection of blood. Participants will receive financial compensation for their participation.

The aim of this study is to demonstrate that a single dose of rabies vaccine can induce an equally rapid and adequate anamnestic antibody response as 3-dose PrEP to revaccination five years later.

D1 (baseline), D57 or D78, Y1, Y2, and Y5 D1 (day of first dose of simulated rabies PEP), Y5 D8 and Y5 D15.

- Study group A – one single intramuscular dose (1 mL) of rabies vaccine (D1) - Study group B – standard three-dose (1 mL) intramuscular PrEP vaccination (D1, D8, D22)