Reactogenicity and safety assessment of an attenuated nanovaccine against scorpion envenomation: Preclinical study

Vaccine. 2017 Dec 4;35(48 Pt B):6657-6663. doi: 10.1016/j.vaccine.2017.10.028. Epub 2017 Oct 20.

Abstract

An attenuated nanovaccine (Nps - V) has been developed to protect humans from fatal scorpion envenomation in at-risk regions. This study was conducted to evaluate the toxicity and the local reactogenicity of the Nps - V nanovaccine developed against Androctonus australis hector (Aah) venom. Assessment of the systemic inflammatory response and serum cytokine levels were evaluated in vaccinated mice with 100μg of irradiated Aah venom (V) encapsulated or not into polymeric calcium-alginate nanoparticles (Nps) and injected by subcutaneous (s.c) route. The local reactogenicity was evaluated by dermal Draize observations and skin tissue analysis at the injection site of vaccinated rabbits with 250 or 500μg of V-loaded into Nps. All animals gained weight and had normal food consumption during the study. Additionally, results showed that the nanoformulation Nps - V did not cause clinical evidence of systemic toxicity in mice or rabbits, a transient edema/erythema at the injection site was only recorded as treatment-related reactogenicity. These results indicated a favorable safety profile for Nps - V and supported its use in superior animal tests, then in a Phase 1 clinical trial.

Keywords: Androctonus australis hector venom; Calcium-alginate nanoparticles; Nanovaccine; Reactogenicity; Safety.

MeSH terms

  • Alginates / administration & dosage*
  • Alginates / adverse effects
  • Alginates / chemistry
  • Animals
  • Cytokines / biosynthesis
  • Cytokines / immunology
  • Drug Evaluation, Preclinical
  • Edema
  • Erythema
  • Glucuronic Acid / administration & dosage
  • Glucuronic Acid / adverse effects
  • Glucuronic Acid / chemistry
  • Hexuronic Acids / administration & dosage
  • Hexuronic Acids / adverse effects
  • Hexuronic Acids / chemistry
  • Humans
  • Mice
  • Nanoparticles / administration & dosage
  • Nanoparticles / adverse effects
  • Nanoparticles / chemistry*
  • Nanoparticles / therapeutic use
  • Nanotechnology / methods
  • Scorpion Venoms / administration & dosage*
  • Scorpion Venoms / adverse effects*
  • Scorpion Venoms / radiation effects*
  • Scorpion Venoms / therapeutic use
  • Vaccination / methods

Substances

  • Alginates
  • Cytokines
  • Hexuronic Acids
  • Scorpion Venoms
  • Glucuronic Acid