Journal Article

An accelerated rabies vaccine schedule based on toll-like receptor 3 (TLR3) agonist PIKA adjuvant augments rabies virus specific antibody and T cell response in healthy adult volunteers

Tham, Christine Y.L., Low, Jenny G., Wijaya, Limin, Bertoletti, Antonio, Chan, Yvonne F.Z., Wang, Lin-Fa, Li, L.T., Wong, Abigail W.L.

2017

Overview

Rabies is a fatal disease where post-exposure prophylaxis (PEP) is crucial in preventing infection. However, deaths even after appropriate PEP, have been reported. The PIKA Rabies vaccine adjuvant is a TLR3 agonist that activates B and T cells leading to a robust immune response. We conducted a phase I, open label, randomized study in healthy adults to assess the safety and immunogenicity of the PIKA Rabies vaccine and an accelerated vaccine regimen. Thirty-seven subjects were randomized into 3 groups: control vaccine classic regimen, PIKA vaccine classic regimen and PIKA vaccine accelerated regimen. Subjects were followed up for safety, rabies virus neutralizing antibodies (RVNA) and T cell responses. Both the control and PIKA Rabies vaccine were well tolerated. All adverse events (AEs) were mild and self-limiting. Seventy-five percent of subjects in the PIKA accelerated regimen achieved a RVNA titer ⩾0.5IU/mL on day 7, compared to 53.9% in the PIKA classic regimen (p=0.411) and 16.7% in control vaccine classic regimen (p=0.012). The PIKA rabies vaccine elicited multi-specific rabies CD4 mediated T cell response already detectable ex vivo at day 7 after vaccination and that was maintained at day 42. The investigational PIKA rabies vaccine was well tolerated and more immunogenic than the commercially available vaccine in healthy adults. Clinical trial registry: The study was registered with clinicaltrials.gov NCT02657161.

• Publisher: Elsevier Ltd,Elsevier Limited
• Subject: adjuvants / Adjuvants, Immunologic - pharmacology / Adult / adults / agonists / Allergy and Immunology / Animals / Antibodies, Neutralizing - biosynthesis / Antibodies, Viral - biosynthesis / CD4-Positive T-Lymphocytes - cytology / CD4-Positive T-Lymphocytes - drug effects / CD4-Positive T-Lymphocytes - immunology / Cercopithecus aethiops / disease control / Gene Expression / Healthy Volunteers / Humans / Immune response / Immunization Schedule / Immunogenicity / Immunogenicity, Vaccine / Laboratories / Lymphocytes / Male / neutralization / Neutralization Tests / neutralizing antibodies / Patient Safety / PIKA rabies vaccine / Post-Exposure Prophylaxis - methods / Prophylaxis / Rabies / Rabies - prevention & control / Rabies lyssavirus / Rabies Vaccines - administration & dosage / Rabies virus / Rabies virus - chemistry / Rabies virus - immunology / Rabies-specific T cell immune response / Safety / T-lymphocytes / Toll-like receptor 3 / Toll-Like Receptor 3 - agonists / Toll-Like Receptor 3 - genetics / Toll-Like Receptor 3 - immunology / Vaccination / Vaccines / Vero Cells / Volunteers