Metabolic, humoral, and cellular responses in adult volunteers immunized with the genetically inactivated pertussis toxin mutant PT-9K/129G

Audino Podda, Luciano Nencioni, M. Teresa De Magistris, Annalisa Di Tommaso, Paola Bossù, Sandra Nuti, Piero Pileri, Samuele Peppoloni, Massimo Bugnoli, Paolo Ruggiero, Ilio Marsili, Alberto D'Errico, Aldo Tagliabue, Rino Rappuoli

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)861-868
Number of pages8
JournalJournal of Experimental Medicine
Volume172
Issue number3
Publication statusPublished - Sep 1 1990

ASJC Scopus subject areas

  • Immunology

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