Rabies virus (inactivated) strain Flury LEP

Table of contents

• What is rabies virus (inactivated) strain Flury LEP?
• How does the rabies vaccine work?
• Which conditions is it used or studied for?
• How is the rabies vaccine given?
• What do the clinical trials show?
• What side effects are known?

What is rabies virus (inactivated) strain Flury LEP?

Rabies virus (inactivated) strain Flury LEP is a killed whole-virus vaccine used to prevent rabies. It is classified as an inactivated whole-virus rabies vaccine (ATC code J07BG01).^[3] The vaccine is produced by growing the fixed-virus strain Flury Low Egg Passage (LEP) in primary cultures of chicken fibroblasts, then inactivating the virus with beta-propiolactone.^[7] The substance is marketed under the trade names Rabipur and RabAvert.^[3][7] It is already authorised as a medicine in the Netherlands, Belgium, Germany and France, with Bavarian Nordic A/S as the authorisation holder.^[3]

How does the rabies vaccine work?

Rabipur contains rabies virus that has been killed. After the vaccine is given, the immune system forms antibodies against the rabies virus. These antibodies protect against infection by the virus that causes rabies. None of the components of the vaccine can cause rabies.^[8] One dose of reconstituted RabAvert contains at least 2.5 IU of rabies antigen.^[7]

Which conditions is it used or studied for?

• Rabies prevention before exposure (pre-exposure prophylaxis) — vaccination given to people at risk of being exposed to rabies, such as travellers or people working with animals.
• Rabies prevention after exposure (post-exposure prophylaxis) — vaccination given after a suspected or proven exposure to rabies through a bite, scratch or lick from an infected animal.^[8]
• Rabies infection and prophylaxis — one registered trial studies booster responses in healthy volunteers primed at least five years earlier.^[6]

How is the rabies vaccine given?

The vaccine is supplied as a powder and solvent for solution for injection in a pre-filled syringe.^[3] It can be given by intramuscular injection or intradermal injection.^[3] RabAvert is intended for intramuscular injection and contains no preservative; it should be used immediately after reconstitution with the supplied sterile diluent.^[7]

What do the clinical trials show?

The EU Clinical Trials Information System lists six interventional trials in which this vaccine is the test substance.^[3] Five are Phase 3 trials; one is a low-intervention pilot study in children.^[3][4] Three trials are completed and three are authorised.^[3][1][2]

The trials focus on pre-exposure prophylaxis schedules. One completed Phase 3 trial with 360 adults compared a 4 x 0.1 mL intradermal priming dose and a 1 x 1.0 mL intramuscular priming dose against the standard of care, measuring the percentage of subjects with rabies antibodies of at least 0.5 IU/mL seven days after a booster.^[3] Another completed Phase 3 trial with 165 participants compared intradermal and intramuscular vaccination, measuring skin-resident rabies-specific T cells after a booster.^[1]

A larger authorised Phase 3 trial with 561 healthy volunteers is testing whether three different priming regimens given at least five years earlier still produce an adequate immune response, defined as RFFIT levels of at least 0.5 IU/mL on day 7 after a single simulated post-exposure booster.^[6] A separate authorised Phase 3 trial with 240 participants is measuring the rise in neutralising antibodies between day 1 and day 8 after revaccination, five years after a single intramuscular priming dose.^[2]

A low-intervention pilot study with 48 children aged 4 to 14 years is assessing pain and usability of different injection techniques, using the Faces Pain Scale-Revised after each vaccination.^[4] The vaccine also appears as an auxiliary medicine in one Phase 1/2 trial of an experimental gene-edited cell therapy for X-linked hyper-IgM syndrome, where it is used to test immune responses.^[5]

What side effects are known?

The package leaflet for Rabipur states that severe allergic reactions are a known risk, and the vaccine must not be given before possible exposure to anyone with a history of severe allergic reaction to the active substance or any ingredient.^[8] The leaflet also notes that because of the seriousness of rabies infection, Rabipur can be given to anyone who has been exposed to rabies, including pregnant women.^[8] Further side effects are listed in section 4 of the leaflet.^[8]