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. Issue 8 (22nd February 2017)

• Record Type: Journal Article
• Authors: Wijaya, Limin; Tham, Christine Y.L.; Chan, Yvonne F.Z.; Wong, Abigail W.L.; Li, L.T.; Wang, Lin-Fa; Bertoletti, Antonio; Low, Jenny G.
• Is Part Of: Vaccine. Volume 35:Issue 8(2017)
• Page Start: 1175
• Page End: 1183
• Publication Date: 2017-02-22
• Subjects: PIKA rabies vaccine -- Safety -- Immunogenicity -- Rabies-specific T cell immune response; ACIP Advisory Committee on Immunization Practices -- AEs adverse events -- CSIRO Commonwealth Scientific and Industrial Research Organization -- CTCAE Common Terminology Criteria for Adverse Events -- ELISPOT enzyme-linked immunosorbent spot -- FAVN Fluorescent antibody virus neutralization -- GlyRab rabies glycoprotein -- IPRV Inactivated and Purified Rabies Virus -- PBMCs Peripheral Blood Mononuclear cells -- MAbs monoclonal antibodies -- MedDRA Medical Dictionary for Regulatory Activities -- mITT modified intent-to-treat -- PEP post-exposure prophylaxis -- PIKA Polyinosinic-Polycytidylic Acid Based Adjuvant -- PP per-protocol -- RIG rabies immunoglobulins -- RVNA rabies virus neutralizing antibodies -- SAEs Serious Adverse Events -- SFU spot-forming units -- TLR3 Toll-like receptor 3 -- WHO World Health Organization; Vaccines -- Periodicals; 615.372
• DOI: 10.1016/j.vaccine.2016.12.031
• Languages: English
• ISSNs: 0264-410X

Abstract

Abstract: Background: 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. Methods: 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. Results: 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 ⩾0.5 IU/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. Conclusion: 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.govNCT02657161 .