A novel rabies vaccine based-on toll-like receptor 3 (TLR3) agonist PIKA adjuvant exhibiting excellent safety and efficacy in animal studies

Virology. 2016 Feb;489:165-72. doi: 10.1016/j.virol.2015.10.029. Epub 2016 Jan 5.

Abstract

Vaccination alone is not sufficiently effective to protect human from post-exposure rabies virus infection due to delayed generation of rabies virus neutralizing antibodies and weak cellular immunity. Therefore, it is vital to develop safer and more efficacious vaccine against rabies. PIKA, a stabilized chemical analog of double-stranded RNA that interacts with TLR3, was employed as adjuvant of rabies vaccine. The efficacy and safety of PIKA rabies vaccine were evaluated. The results showed that PIKA rabies vaccine enhanced both humoral and cellular immunity. After viral challenge, PIKA rabies vaccine protected 70-80% of animals, while the survival rate of non-adjuvant vaccine group (control) was 20-30%. According to the results of toxicity tests, PIKA and PIKA rabies vaccine are shown to be well tolerated in mice. Thus, this study indicates that PIKA rabies vaccine is an effective and safe vaccine which has the potential to develop next-generation rabies vaccine and encourage the start of clinical studies.

Keywords: Efficacy; PIKA adjuvant; Rabies vaccine; Safety.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Viral / immunology
  • Drug Evaluation, Preclinical
  • Female
  • Humans
  • Immunity, Cellular
  • Male
  • Mice
  • Mice, Inbred BALB C
  • RNA, Double-Stranded / administration & dosage
  • RNA, Double-Stranded / adverse effects
  • RNA, Double-Stranded / genetics
  • RNA, Double-Stranded / immunology*
  • Rabies / immunology*
  • Rabies / prevention & control
  • Rabies / virology
  • Rabies Vaccines / administration & dosage
  • Rabies Vaccines / adverse effects
  • Rabies Vaccines / immunology*
  • Rabies virus / genetics
  • Rabies virus / immunology*
  • Toll-Like Receptor 3 / agonists*
  • Toll-Like Receptor 3 / immunology

Substances

  • Antibodies, Viral
  • RNA, Double-Stranded
  • Rabies Vaccines
  • TLR3 protein, human
  • Toll-Like Receptor 3