Serological correlates of protection and long-term efficacy of a novel recombinant protective antigen-based anthrax vaccine in a rabbit model

Vaccine. 2025 May 31:57:127212. doi: 10.1016/j.vaccine.2025.127212. Epub 2025 May 9.

Abstract

The novel anthrax vaccine candidate GC1109, composed of recombinant protective antigen, has shown robust antibody responses and safety in preclinical and clinical studies. However, the assessment of GC1109 vaccine efficacy was limited in a rodent model and could not be applied in clinical studies due to ethical issues. In this study, we aim to provide predictive insights for human applications of GC1109 by examining the correlation between anthrax toxin-neutralizing antibodies (TNAs) and protection against Bacillus anthracis infection in rabbit. The threshold level of TNAs necessary for protection was assessed following subcutaneous (s.c) challenge with lethal B. anthracis spores. In addition, the longevity of immunity in GC1109-vaccinated rabbits was investigated. A positive correlation between TNA levels and survival was observed, indicating their potential as a predictor of protection in humans. The 50 % neutralization factor (NF50) value of 0.5 was associated with a 70 % probability of survival, establishing this value as a surrogate marker for protective efficacy. Long-term protection was confirmed, with the GC1109-vaccinated group exhibiting significantly higher survival rates (91.7 %) than the control group (8.3 %) at 12 months post-vaccination. These findings highlight the protective efficacy and durability of GC1109-induced immunity against lethal B. anthracis challenge. The study supports the continued development of GC1109 as a viable anthrax vaccine candidate and underscores its potential for emergency preparedness in Korea.

Keywords: Anthrax vaccine; GC1109; Long-term protection; Rabbit model; Survival; Toxin neutralization activity.

MeSH terms

  • Animals
  • Anthrax Vaccines* / administration & dosage
  • Anthrax Vaccines* / immunology
  • Anthrax* / immunology
  • Anthrax* / prevention & control
  • Antibodies, Bacterial / blood
  • Antibodies, Bacterial / immunology
  • Antibodies, Neutralizing / blood
  • Antibodies, Neutralizing / immunology
  • Antigens, Bacterial* / genetics
  • Antigens, Bacterial* / immunology
  • Bacillus anthracis / immunology
  • Bacterial Toxins* / genetics
  • Bacterial Toxins* / immunology
  • Disease Models, Animal
  • Female
  • Rabbits
  • Vaccine Efficacy
  • Vaccines, Synthetic / administration & dosage
  • Vaccines, Synthetic / immunology

Substances

  • Anthrax Vaccines
  • Antigens, Bacterial
  • Bacterial Toxins
  • Antibodies, Bacterial
  • anthrax toxin
  • Antibodies, Neutralizing
  • Vaccines, Synthetic