title: 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.
abstract: 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.
authors.affiliation: Department of Infectious Diseases, Singapore General Hospital, 20 College Road, Singapore 169856, Singapore. Electronic address: limin.wijaya@singhealth.com.sg.
authors.forename: Limin
authors.initials: L
authors.lastname: Wijaya
authors.affiliation: Singapore Institute for Clinical Sciences, Agency for Science Technology and Research (A*STAR), 30 Medical Drive, Singapore 117609, Singapore; NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, 28 Medical Drive, Singapore 117456, Singapore. Electronic address: ylin@duke-nus.edu.sg.
authors.forename: Christine Y L
authors.initials: CYL
authors.lastname: Tham
authors.affiliation: Department of Infectious Diseases, Singapore General Hospital, 20 College Road, Singapore 169856, Singapore. Electronic address: yvonne.chan2@mohh.com.sg.
authors.forename: Yvonne F Z
authors.initials: YFZ
authors.lastname: Chan
authors.affiliation: Department of Infectious Diseases, Singapore General Hospital, 20 College Road, Singapore 169856, Singapore. Electronic address: abigail.wong.w.l@sgh.com.sg.
authors.forename: Abigail W L
authors.initials: AWL
authors.lastname: Wong
authors.affiliation: Yisheng Biopharma (Singapore) Pte. Ltd., 20 Maxwell Road, Maxwell House 07-15A, Singapore 069113, Singapore. Electronic address: lietao.li@gmail.com.
authors.forename: L T
authors.initials: LT
authors.lastname: Li
authors.affiliation: Program in Emerging Infectious Diseases, DUKE-NUS Medical School, 8 College Road, Singapore 169857, Singapore. Electronic address: linfa.wang@duke-nus.edu.sg.
authors.forename: Lin-Fa
authors.initials: LF
authors.lastname: Wang
authors.affiliation: Program in Emerging Infectious Diseases, DUKE-NUS Medical School, 8 College Road, Singapore 169857, Singapore; Singapore Institute for Clinical Sciences, Agency for Science Technology and Research (A*STAR), 30 Medical Drive, Singapore 117609, Singapore. Electronic address: antonio@duke-nus.edu.sg.
authors.forename: Antonio
authors.initials: A
authors.lastname: Bertoletti
authors.affiliation: Department of Infectious Diseases, Singapore General Hospital, 20 College Road, Singapore 169856, Singapore. Electronic address: jenny.low@singhealth.com.sg.
authors.forename: Jenny G
authors.initials: JG
authors.lastname: Low
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000328:Adult; D000818:Animals; D057134:Antibodies, Neutralizing / Q000096:biosynthesis*; D000914:Antibodies, Viral / Q000096:biosynthesis*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D002522:Chlorocebus aethiops; D015870:Gene Expression; D064368:Healthy Volunteers; D006801:Humans; D007115:Immunization Schedule; D000071497:Immunogenicity, Vaccine; D008297:Male; D009500:Neutralization Tests; D061214:Patient Safety; D056990:Post-Exposure Prophylaxis / Q000379:methods; D011818:Rabies / Q000517:prevention & control; D011819:Rabies Vaccines / Q000008:administration & dosage*; D011820:Rabies virus / Q000737:chemistry / Q000276:immunology; D051196:Toll-Like Receptor 3 / Q000819:agonists* / Q000235:genetics / Q000276:immunology; D014611:Vaccination; D014709:Vero Cells
chemical_list: D000276:Adjuvants, Immunologic; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D011819:Rabies Vaccines; C495344:TLR3 protein, human; D051196:Toll-Like Receptor 3
keywords: Immunogenicity; PIKA rabies vaccine; Rabies-specific T cell immune response; Safety