PMID- 28118938 OWN - NLM STAT- MEDLINE DCOM- 20171208 LR - 20191210 IS - 1873-2518 (Electronic) IS - 0264-410X (Linking) VI - 35 IP - 8 DP - 2017 Feb 22 TI - 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. PG - 1175-1183 LID - S0264-410X(16)31256-7 [pii] LID - 10.1016/j.vaccine.2016.12.031 [doi] AB - 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 ⩾0.5IU/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. 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.gov NCT02657161. CI - Copyright (c) 2017 Elsevier Ltd. All rights reserved. FAU - Wijaya, Limin AU - Wijaya L AD - Department of Infectious Diseases, Singapore General Hospital, 20 College Road, Singapore 169856, Singapore. Electronic address: limin.wijaya@singhealth.com.sg. FAU - Tham, Christine Y L AU - Tham CYL AD - 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. FAU - Chan, Yvonne F Z AU - Chan YFZ AD - Department of Infectious Diseases, Singapore General Hospital, 20 College Road, Singapore 169856, Singapore. Electronic address: yvonne.chan2@mohh.com.sg. FAU - Wong, Abigail W L AU - Wong AWL AD - Department of Infectious Diseases, Singapore General Hospital, 20 College Road, Singapore 169856, Singapore. Electronic address: abigail.wong.w.l@sgh.com.sg. FAU - Li, L T AU - Li LT AD - Yisheng Biopharma (Singapore) Pte. Ltd., 20 Maxwell Road, Maxwell House 07-15A, Singapore 069113, Singapore. Electronic address: lietao.li@gmail.com. FAU - Wang, Lin-Fa AU - Wang LF AD - Program in Emerging Infectious Diseases, DUKE-NUS Medical School, 8 College Road, Singapore 169857, Singapore. Electronic address: linfa.wang@duke-nus.edu.sg. FAU - Bertoletti, Antonio AU - Bertoletti A AD - 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. FAU - Low, Jenny G AU - Low JG AD - Department of Infectious Diseases, Singapore General Hospital, 20 College Road, Singapore 169856, Singapore. Electronic address: jenny.low@singhealth.com.sg. LA - eng SI - ClinicalTrials.gov/NCT02657161 PT - Clinical Trial, Phase I PT - Journal Article PT - Randomized Controlled Trial DEP - 20170122 PL - Netherlands TA - Vaccine JT - Vaccine JID - 8406899 RN - 0 (Adjuvants, Immunologic) RN - 0 (Antibodies, Neutralizing) RN - 0 (Antibodies, Viral) RN - 0 (Rabies Vaccines) RN - 0 (TLR3 protein, human) RN - 0 (Toll-Like Receptor 3) SB - IM MH - Adjuvants, Immunologic/*pharmacology MH - Adult MH - Animals MH - Antibodies, Neutralizing/*biosynthesis MH - Antibodies, Viral/*biosynthesis MH - CD4-Positive T-Lymphocytes/cytology/*drug effects/immunology MH - Chlorocebus aethiops MH - Gene Expression MH - Healthy Volunteers MH - Humans MH - Immunization Schedule MH - Immunogenicity, Vaccine MH - Male MH - Neutralization Tests MH - Patient Safety MH - Post-Exposure Prophylaxis/methods MH - Rabies/prevention & control MH - Rabies Vaccines/*administration & dosage MH - Rabies virus/chemistry/immunology MH - Toll-Like Receptor 3/*agonists/genetics/immunology MH - Vaccination MH - Vero Cells OTO - NOTNLM OT - Immunogenicity OT - PIKA rabies vaccine OT - Rabies-specific T cell immune response OT - Safety EDAT- 2017/01/26 06:00 MHDA- 2017/12/09 06:00 CRDT- 2017/01/26 06:00 PHST- 2016/10/08 00:00 [received] PHST- 2016/12/14 00:00 [revised] PHST- 2016/12/14 00:00 [accepted] PHST- 2017/01/26 06:00 [pubmed] PHST- 2017/12/09 06:00 [medline] PHST- 2017/01/26 06:00 [entrez] AID - S0264-410X(16)31256-7 [pii] AID - 10.1016/j.vaccine.2016.12.031 [doi] PST - ppublish SO - Vaccine. 2017 Feb 22;35(8):1175-1183. doi: 10.1016/j.vaccine.2016.12.031. Epub 2017 Jan 22.