Metabolic, humoral, and cellular responses in adult volunteers immunized with the genetically inactivated pertussis toxin mutant PT-9K/129G.
PT-9K/129G, a nontoxic mutant of pertussis toxin (PT) obtained by genetic manipulation, has been shown in animal models to be a promising candidate for new vaccines against whooping cough. To assess the safety and the immunogenicity of PT-9K/129G in humans, a pilot study has been performed in adult volunteers. The protein was found to be safe, capable of inducing high titers of toxin-neutralizing antibodies, and capable of generating immunological memory. In fact, vaccination caused an increase of cell-mediated response to PT, PT-9K/129G, S1 subunit, and B oligomer, indicating that memory T cells are induced by the vaccine. Since PT-9K/129G is mitogenic for T lymphocytes in vitro, it was investigated whether this activity is also present in vivo. No variation was observed in the proportion of T cells (CD3+), T helper cells (CD4+), and cytotoxic T cells (CD8+), as well as in that of other lymphoid populations, by FACS analysis. Interestingly, no thorough correlation was found between humoral and cellular responses. In one case, a very high cellular response was present in absence of detectable antibodies, suggesting that the antibody response, which is the only parameter measured in most clinical trials, may not give a complete picture of the response induced by a vaccine.
Sclavo Research Center, Sienna, Italy.
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Podda
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Nencioni
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De Magistris
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Di Tommaso
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Bossù
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Nuti
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Pileri
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Peppoloni
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Bugnoli
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Ruggiero
D000328:Adult; D000917:Antibody Formation / Q000187:drug effects*; D001786:Blood Glucose / Q000378:metabolism; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects*; D007328:Insulin / Q000097:blood; D007694:Killer Cells, Natural / Q000276:immunology; D007958:Leukocyte Count; D009154:Mutation; D037342:Pertussis Toxin; D010567:Pertussis Vaccine; D010865:Pilot Projects; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D010566:Virulence Factors, Bordetella / Q000009:adverse effects / Q000235:genetics / Q000276:immunology*
D001786:Blood Glucose; D007328:Insulin; C000597951:PT-9K-129G vaccine; D010567:Pertussis Vaccine; D010566:Virulence Factors, Bordetella; D037342:Pertussis Toxin