Immunisation with canarypox virus expressing rabies glycoprotein

Area of Science:

• Virology
• Immunology
• Vaccinology

Background:

• Poxviruses are effective gene vectors, but vaccinia virus safety is a concern.
• Avian poxviruses like canarypox offer a safer alternative due to abortive replication in mammalian cells.
• Canarypox virus enables presentation of viral antigens to the immune system.

Purpose of the Study:

• To evaluate the safety and efficacy of a recombinant canarypox virus vector (ALVAC-RG) expressing the rabies glycoprotein G gene.
• To assess the immunogenicity and safety of ALVAC-RG in a phase 1 clinical trial involving human volunteers.

Main Methods:

• Recombinant canarypox virus (ALVAC-RG) encoding the rabies glycoprotein G gene was constructed.
• Safety and efficacy were tested in animals, followed by a phase 1 clinical trial with 25 volunteers.
• Volunteers received subcutaneous injections of ALVAC-RG at different doses or a human diploid cell culture vaccine (HDC).

Main Results:

• ALVAC-RG induced rabies neutralising antibodies in volunteers, with higher doses showing greater efficacy.
• Antibody levels in the highest ALVAC-RG dose group approached protective levels seen in animals.
• A booster dose at 6 months elicited a recall immune response in all vaccinated groups.
• Reported side-effects were mild, short-lived, and comparable to the HDC vaccine.

Conclusions:

• Non-replicating poxviruses, such as canarypox, are potential vectors for human vaccination.
• ALVAC-RG demonstrated an acceptable safety profile and induced an immune response against rabies.
• Further trials with higher doses and alternative administration routes are warranted for canarypox-virus recombinants.