Preclinical safety study of a recombinant Streptococcus pyogenes vaccine formulated with aluminum adjuvant

J Appl Toxicol. 2017 Feb;37(2):222-230. doi: 10.1002/jat.3349. Epub 2016 May 30.


A recombinant vaccine composed of a fusion protein formulated with aluminum hydroxide adjuvant is under development for protection against diseases caused by Streptococcus pyogenes. The safety and local reactogenicity of the vaccine was assessed by a comprehensive series of clinical, pathologic and immunologic tests in preclinical experiments. Outbred mice received three intramuscular injections of 1/5th of the human dose (0.1 ml) and rabbits received two injections of the full human dose. Control groups received adjuvant or protein antigen. The vaccine did not cause clinical evidence of systemic toxicity in mice or rabbits. There was a transient increase of peripheral blood neutrophils after the third vaccination of mice. In addition, the concentration of acute phase proteins serum amyloid A and haptoglobin was significantly increased 1 day after injection of the vaccine in mice. There was mild transient swelling and erythema of the injection site in both mice and rabbits. Treatment-related pathology was limited to inflammation at the injection site and accumulation of adjuvant-containing macrophages in the draining lymph nodes. In conclusion, the absence of clinical toxicity in two animal species suggest that the vaccine is safe for use in a phase I human clinical trial. Copyright © 2016 John Wiley & Sons, Ltd.

Keywords: Streptococcus pyogenes; acute phase proteins; injection site; lymph nodes; preclinical safety; vaccine.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Adjuvants, Immunologic / adverse effects*
  • Aluminum Hydroxide / administration & dosage
  • Aluminum Hydroxide / adverse effects*
  • Aluminum Hydroxide / immunology
  • Animals
  • Antibodies, Bacterial / blood
  • Bacterial Proteins / immunology*
  • Dose-Response Relationship, Drug
  • Drug Evaluation, Preclinical
  • Exotoxins / immunology*
  • Female
  • Injection Site Reaction
  • Male
  • Mice, Inbred Strains
  • Rabbits
  • Recombinant Fusion Proteins
  • Streptococcal Vaccines / administration & dosage
  • Streptococcal Vaccines / adverse effects*
  • Streptococcal Vaccines / immunology
  • Streptococcus pyogenes / immunology*


  • Adjuvants, Immunologic
  • Antibodies, Bacterial
  • Bacterial Proteins
  • Exotoxins
  • Recombinant Fusion Proteins
  • Streptococcal Vaccines
  • erythrogenic toxin
  • Aluminum Hydroxide