Abstract <p><i>Bordetella pertussis</i>, a gram-negative bacterium responsible for whooping cough, poses severe health risks, especially to young children. However, the disease can be prevented by immunization with whole-cell pertussis vaccines and acellular pertussis vaccines containing 2–5 purified <i>B. pertussis</i> antigens, of which chemically detoxified pertussis toxin is the main protective component. While current vaccines have proven effective, concerns over high reactogenicity of whole-cell pertussis vaccines and the waning immunity to acellular pertussis vaccines formulations underscore the need for improved pertussis vaccines. Genetically detoxified pertussis toxin is an attractive vaccine candidate because it retains most of the structural properties of native pertussis toxin and better preserves the protective epitopes compared to detoxified pertussis toxin. In this study, we developed a candidate vaccine based on a genetically detoxified pertussis toxin S1 subunit, gd15PTxS1. We evaluated humoral and cellular immunogenicity of gd15PTxS1 in a murine model and demonstrated significant anti-PTx IgG seroconversion and a balanced Th1/Th2/Th17 T-cell response, with gd15PTxS1 inducing robust cytotoxic and helper T-cell activation comparable to that of the whole-cell pertussis vaccines. Our results show that gd15PTxS1 is highly immunogenic in mice and is a promising vaccine candidate for further protectivity studies.</p>

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Humoral and Cellular Immune Response to the Genetically Detoxified S1 Subunit of Pertussis Toxin in Mice

  • V. A. Shokina,
  • A. V. Maleeva,
  • V. P. Volok,
  • O. V. Shcherbakova,
  • N. E. Postika,
  • A. V. Melikhova,
  • D. Y. Mokhirev,
  • A. A. Tikhonova,
  • D. Engin,
  • A. V. Lukina-Gronskaya,
  • I. S. Rog,
  • I. K. Chudinov,
  • A. A. Lazareva,
  • A. V. Kovalenko,
  • Y. E. Kuzmina,
  • O. V. Fedorov,
  • A. S. Speranskaya,
  • A. V. Kudriavtsev

摘要

Abstract

Bordetella pertussis, a gram-negative bacterium responsible for whooping cough, poses severe health risks, especially to young children. However, the disease can be prevented by immunization with whole-cell pertussis vaccines and acellular pertussis vaccines containing 2–5 purified B. pertussis antigens, of which chemically detoxified pertussis toxin is the main protective component. While current vaccines have proven effective, concerns over high reactogenicity of whole-cell pertussis vaccines and the waning immunity to acellular pertussis vaccines formulations underscore the need for improved pertussis vaccines. Genetically detoxified pertussis toxin is an attractive vaccine candidate because it retains most of the structural properties of native pertussis toxin and better preserves the protective epitopes compared to detoxified pertussis toxin. In this study, we developed a candidate vaccine based on a genetically detoxified pertussis toxin S1 subunit, gd15PTxS1. We evaluated humoral and cellular immunogenicity of gd15PTxS1 in a murine model and demonstrated significant anti-PTx IgG seroconversion and a balanced Th1/Th2/Th17 T-cell response, with gd15PTxS1 inducing robust cytotoxic and helper T-cell activation comparable to that of the whole-cell pertussis vaccines. Our results show that gd15PTxS1 is highly immunogenic in mice and is a promising vaccine candidate for further protectivity studies.