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

Vaccine. 2017 Feb 22;35(8):1175-1183. doi: 10.1016/j.vaccine.2016.12.031. Epub 2017 Jan 22.


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 NCT02657161.

Keywords: Immunogenicity; PIKA rabies vaccine; Rabies-specific T cell immune response; Safety.

Publication types

  • Clinical Trial, Phase I
  • Randomized Controlled Trial

MeSH terms

  • Adjuvants, Immunologic / pharmacology*
  • Adult
  • Animals
  • Antibodies, Neutralizing / biosynthesis*
  • Antibodies, Viral / biosynthesis*
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / drug effects*
  • CD4-Positive T-Lymphocytes / immunology
  • Chlorocebus aethiops
  • Gene Expression
  • Healthy Volunteers
  • Humans
  • Immunization Schedule
  • Immunogenicity, Vaccine
  • Male
  • Neutralization Tests
  • Patient Safety
  • Post-Exposure Prophylaxis / methods
  • Rabies / prevention & control
  • Rabies Vaccines / administration & dosage*
  • Rabies virus / chemistry
  • Rabies virus / immunology
  • Toll-Like Receptor 3 / agonists*
  • Toll-Like Receptor 3 / genetics
  • Toll-Like Receptor 3 / immunology
  • Vaccination
  • Vero Cells


  • Adjuvants, Immunologic
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Rabies Vaccines
  • TLR3 protein, human
  • Toll-Like Receptor 3

Associated data