Acellular Pertussis Vaccines

1. Kathryn Edwards, MD* 1. 2. *Vanderbilt University Medical Center Nashville, TN Dr Edwards has funding for research from Connaught and Lederle-Praxis and is on their speaker’s bureaus. She also is a consultant for Smith-Kline Beecham Co. 1. Pertussis. Committee on Infectious Diseases. 1997 Red Book . 24th ed. 1994:394-407 American Academy of Pediatrics Elk Grove Village, Ill 2. Report of the Nationwide Multicenter Acellular Pertussis Trial . Decker MD, Edwards KM. Pediatrics . 1995;96(suppl):547-603 [OpenUrl][1][Abstract/FREE Full Text][2] 3. Bordetella Pertussis (Whooping Cough) . Cattaneo L, Edwards KM. Semin Pediatr Infect Dis . 1995;6:107-118 4. A Controlled Trial of Two Acellular Vaccines and One Whole-cell Vaccine Against Pertussis . Greco D, Salmaso S, Mastrantonis P, et al. N Engl J Med . 1996;334:341-348 [OpenUrl][3][CrossRef][4][PubMed][5][Web of Science][6] 5. A Controlled Trial of a Two-component Acellular, a Five-component Acellular, and a Whole-cell Pertussis Vaccine . Gustafsson L, Hallander HO, Olin P, Reizenstein E, Storsaeter J. N Engl J Med . 1996;334:349-355 [OpenUrl][7][CrossRef][8][PubMed][9][Web of Science][10] Bordetella pertussis , a fastidious, Gram-negative pleomorphic bacillus first isolated by Bordet and Gengou in 1906, has a marked tropism for ciliated respiratory tract epithelial cells and does not invade the bloodstream. The organism produces multiple antigens that have been the focus of extensive research in the past decade; their isolation and purification has made possible the development of new acellular pertussis vaccines that feature four major antigenic components: pertussis toxin, filamentous hemagglutinin, agglutinogens (fimbriae), and pertactin (Table 1⇓ ). View this table: Table 1. Components Considered for Incorporation into Acellular Vaccine1 Pertussis toxin (PT), also termed lymphocytosis-promoting factor, induces many of the biologic activities of the organism: histamine sensitization, lymphocytosis-promoting activity, pancreatic islet cell activation, and immune response enhancement. PT is composed of several subunits and has a structure similar to other bacterial toxins such as diphtheria. When administered to mice, PT induces antibodies that protect against lethal respiratory and intracerebral challenge with live B pertussis organisms. Many investigators believe PT has a central role in providing clinical protection for humans. For incorporation into a vaccine, active toxin must be inactivated (or toxoided) either chemically or genetically. Filamentous hemagglutinin (FHA), a component of the cell wall, is believed to be crucial for the attachment of organisms to the respiratory epithelium. Mice immunized with FHA are protected against lethal respiratory challenge with pertussis but not against intracerebral challenge. Agglutinogens are fimbrial-associated surface components that stimulate production of agglutinating antibodies. Although pertussis carries several different agglutinogens, three types (1, 2, and 3) occur in various combinations … [1]: {openurl}?query=rft.jtitle%253DPediatrics%26rft.stitle%253DPediatrics%26rft.issn%253D0031-4005%26rft.aulast%253DKlein%26rft.auinit1%253DD.%2BL.%26rft.volume%253D96%26rft.issue%253D3%26rft.spage%253D547%26rft.epage%253D548%26rft.atitle%253DMulticenter%2BAcellular%2BPertussis%2BVaccine%2BTrial%253A%2BA%2BNational%2BInstitutes%2Bof%2BHealth%2BPerspective%26rft_id%253Dinfo%253Apmid%252F7659474%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/ijlink?linkType=ABST&journalCode=pediatrics&resid=96/3/547&atom=%2Fpedsinreview%2F19%2F2%2F68.atom [3]: {openurl}?query=rft.jtitle%253DNew%2BEngland%2BJournal%2Bof%2BMedicine%26rft.stitle%253DNEJM%26rft.issn%253D0028-4793%26rft.aulast%253DGreco%26rft.auinit1%253DD.%26rft.volume%253D334%26rft.issue%253D6%26rft.spage%253D341%26rft.epage%253D349%26rft.atitle%253DA%2BControlled%2BTrial%2Bof%2BTwo%2BAcellular%2BVaccines%2Band%2BOne%2BWhole-Cell%2BVaccine%2Bagainst%2BPertussis%26rft_id%253Dinfo%253Adoi%252F10.1056%252FNEJM199602083340601%26rft_id%253Dinfo%253Apmid%252F8538704%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [4]: /lookup/external-ref?access_num=10.1056/NEJM199602083340601&link_type=DOI [5]: /lookup/external-ref?access_num=8538704&link_type=MED&atom=%2Fpedsinreview%2F19%2F2%2F68.atom [6]: /lookup/external-ref?access_num=A1996TT48700001&link_type=ISI [7]: {openurl}?query=rft.jtitle%253DNew%2BEngland%2BJournal%2Bof%2BMedicine%26rft.stitle%253DNEJM%26rft.issn%253D0028-4793%26rft.aulast%253DGustafsson%26rft.auinit1%253DL.%26rft.volume%253D334%26rft.issue%253D6%26rft.spage%253D349%26rft.epage%253D356%26rft.atitle%253DA%2BControlled%2BTrial%2Bof%2Ba%2BTwo-Component%2BAcellular%252C%2Ba%2BFive-Component%2BAcellular%252C%2Band%2Ba%2BWhole-Cell%2BPertussis%2BVaccine%26rft_id%253Dinfo%253Adoi%252F10.1056%252FNEJM199602083340602%26rft_id%253Dinfo%253Apmid%252F8538705%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [8]: /lookup/external-ref?access_num=10.1056/NEJM199602083340602&link_type=DOI [9]: /lookup/external-ref?access_num=8538705&link_type=MED&atom=%2Fpedsinreview%2F19%2F2%2F68.atom [10]: /lookup/external-ref?access_num=A1996TT48700002&link_type=ISI