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.
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Selected References
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- Cherry J. D. 'Pertussis vaccine encephalopathy': it is time to recognize it as the myth that it is. JAMA. 1990 Mar 23;263(12):1679–1680. [PubMed] [Google Scholar]
- De Magistris M. T., Romano M., Bartoloni A., Rappuoli R., Tagliabue A. Human T cell clones define S1 subunit as the most immunogenic moiety of pertussis toxin and determine its epitope map. J Exp Med. 1989 May 1;169(5):1519–1532. doi: 10.1084/jem.169.5.1519. [DOI] [PMC free article] [PubMed] [Google Scholar]
- De Magistris M. T., Romano M., Nuti S., Rappuoli R., Tagliabue A. Dissecting human T cell responses against Bordetella species. J Exp Med. 1988 Oct 1;168(4):1351–1362. doi: 10.1084/jem.168.4.1351. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ferrick D. A., Ohashi P. S., Wallace V., Schilham M., Mak T. W. Thymic ontogeny and selection of alpha beta and gamma delta T cells. Immunol Today. 1989 Dec;10(12):403–407. doi: 10.1016/0167-5699(89)90035-2. [DOI] [PubMed] [Google Scholar]
- Fleischer B., Schrezenmeier H. T cell stimulation by staphylococcal enterotoxins. Clonally variable response and requirement for major histocompatibility complex class II molecules on accessory or target cells. J Exp Med. 1988 May 1;167(5):1697–1707. doi: 10.1084/jem.167.5.1697. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hewlett E. L., Sauer K. T., Myers G. A., Cowell J. L., Guerrant R. L. Induction of a novel morphological response in Chinese hamster ovary cells by pertussis toxin. Infect Immun. 1983 Jun;40(3):1198–1203. doi: 10.1128/iai.40.3.1198-1203.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Marrack P., Blackman M., Kushnir E., Kappler J. The toxicity of staphylococcal enterotoxin B in mice is mediated by T cells. J Exp Med. 1990 Feb 1;171(2):455–464. doi: 10.1084/jem.171.2.455. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Miller D. L., Ross E. M., Alderslade R., Bellman M. H., Rawson N. S. Pertussis immunisation and serious acute neurological illness in children. Br Med J (Clin Res Ed) 1981 May 16;282(6276):1595–1599. doi: 10.1136/bmj.282.6276.1595. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Muller A. S., Leeuwenburg J., Pratt D. S. Pertussis: epidemiology and control. Bull World Health Organ. 1986;64(2):321–331. [PMC free article] [PubMed] [Google Scholar]
- Nencioni L., Pizza M., Bugnoli M., De Magistris T., Di Tommaso A., Giovannoni F., Manetti R., Marsili I., Matteucci G., Nucci D. Characterization of genetically inactivated pertussis toxin mutants: candidates for a new vaccine against whooping cough. Infect Immun. 1990 May;58(5):1308–1315. doi: 10.1128/iai.58.5.1308-1315.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nicosia A., Bartoloni A., Perugini M., Rappuoli R. Expression and immunological properties of the five subunits of pertussis toxin. Infect Immun. 1987 Apr;55(4):963–967. doi: 10.1128/iai.55.4.963-967.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Olin P., Storsaeter J., Romanus V. The efficacy of acellular pertussis vaccine. JAMA. 1989 Jan 27;261(4):560–560. [PubMed] [Google Scholar]
- Pittman M. Pertussis toxin: the cause of the harmful effects and prolonged immunity of whooping cough. A hypothesis. Rev Infect Dis. 1979 May-Jun;1(3):401–412. doi: 10.1093/clinids/1.3.401. [DOI] [PubMed] [Google Scholar]
- Pittman M. The concept of pertussis as a toxin-mediated disease. Pediatr Infect Dis. 1984 Sep-Oct;3(5):467–486. doi: 10.1097/00006454-198409000-00019. [DOI] [PubMed] [Google Scholar]
- Pizza M., Covacci A., Bartoloni A., Perugini M., Nencioni L., De Magistris M. T., Villa L., Nucci D., Manetti R., Bugnoli M. Mutants of pertussis toxin suitable for vaccine development. Science. 1989 Oct 27;246(4929):497–500. doi: 10.1126/science.2683073. [DOI] [PubMed] [Google Scholar]
- Sato H., Sato Y. Protective antigens of Bordetella pertussis mouse-protection test against intracerebral and aerosol challenge of B. pertussis. Dev Biol Stand. 1985;61:461–467. [PubMed] [Google Scholar]
- Sato Y., Kimura M., Fukumi H. Development of a pertussis component vaccine in Japan. Lancet. 1984 Jan 21;1(8369):122–126. doi: 10.1016/s0140-6736(84)90061-8. [DOI] [PubMed] [Google Scholar]
- Sekura R. D., Fish F., Manclark C. R., Meade B., Zhang Y. L. Pertussis toxin. Affinity purification of a new ADP-ribosyltransferase. J Biol Chem. 1983 Dec 10;258(23):14647–14651. [PubMed] [Google Scholar]
- Sekura R. D., Zhang Y. L., Roberson R., Acton B., Trollfors B., Tolson N., Shiloach J., Bryla D., Muir-Nash J., Koeller D. Clinical, metabolic, and antibody responses of adult volunteers to an investigational vaccine composed of pertussis toxin inactivated by hydrogen peroxide. J Pediatr. 1988 Nov;113(5):806–813. doi: 10.1016/s0022-3476(88)80005-2. [DOI] [PubMed] [Google Scholar]
- Storsaeter J., Olin P., Renemar B., Lagergård T., Norberg R., Romanus V., Tiru M. Mortality and morbidity from invasive bacterial infections during a clinical trial of acellular pertussis vaccines in Sweden. Pediatr Infect Dis J. 1988 Sep;7(9):637–645. doi: 10.1097/00006454-198809000-00008. [DOI] [PubMed] [Google Scholar]
- Uchiyama T., Tadakuma T., Imanishi K., Araake M., Saito S., Yan X. J., Fujikawa H., Igarashi H., Yamaura N. Activation of murine T cells by toxic shock syndrome toxin-1. The toxin-binding structures expressed on murine accessory cells are MHC class II molecules. J Immunol. 1989 Nov 15;143(10):3175–3182. [PubMed] [Google Scholar]
- Wardlaw A. C., Parton R. Bordetella pertussis toxins. Pharmacol Ther. 1982;19(1):1–53. doi: 10.1016/0163-7258(82)90041-9. [DOI] [PubMed] [Google Scholar]
- White J., Herman A., Pullen A. M., Kubo R., Kappler J. W., Marrack P. The V beta-specific superantigen staphylococcal enterotoxin B: stimulation of mature T cells and clonal deletion in neonatal mice. Cell. 1989 Jan 13;56(1):27–35. doi: 10.1016/0092-8674(89)90980-x. [DOI] [PubMed] [Google Scholar]
- Yagi J., Baron J., Buxser S., Janeway C. A., Jr Bacterial proteins that mediate the association of a defined subset of T cell receptor:CD4 complexes with class II MHC. J Immunol. 1990 Feb 1;144(3):892–901. [PubMed] [Google Scholar]