The Immunology of Bordetella pertussis Infection

Biologicals (1999) 27, 77 A icle No. biol.1999.0183, a ailable online a h p://www.idealib a y.com on The Immunology o Bo de ella pe ussis In ec ion Kings on H. G. Mills*, Ma k Ryan, Pe e McGui k, Fiona G i in, Ge aldine Mu phy and Be na d Mahon In ec ion and Immuni y G oup, Depa men o Biology, Na ional Uni e si y o I eland, Maynoo h, Co. Kilda e, I eland Despi e he weal h o in o ma ion on he pa ho- genesis, i ulence and an igenici y o Bo de alla pe ussis and he success ul de elopmen o e#ica- cious acellula pe ussis accines, he mechanism o accine induced p o ec ion agains Bo de alla pe ussis in man is s ill poo ly unde s ood. Using mu ine models, we and o he s ha e p e iously epo ed e idence o he in ol emen o T cells in p o ec i e immuni y. Based on he obse a ion ha espi a o y in ec ion wi h Bo de alla pe ussis induces po en and pe sis en immuni y, we ha e s udies he induc ion o T cell subse s induced by na u al in ec ion o by immuniza ion wi h whole cell and acellula accines in child en. Fu he mo e we ha e employed he mu ine espi a o y challenge model in expe imen s ha pe mi ed manipula ion o he immune sys em in an a emp o p o ide mo e di ec e idence o he ole o dis inc a ms o he immune esponse in p o ec ion agains Bo de alla pe ussis. Th ough collabo a ion wi h Jann S o sae e , Lenna Nillson and Lie Go he o s in Sweden, Knu Øyma in No way, Elizabe h Mille in London and Fiona Shackley in Ox o d, we ha e gained access o aluable clinical samples o he assess- men o cellula immune esponses o Bo de alla pe ussis in child en. Ini ial in es iga ions o cy okine p oduc ion by pe iphe al blood T cells om child en eco e ing om whooping cough sug- ges ed ha immuni y gene a ed by na u al in ec ion is media ed by Th1 cells. Fu he mo e analysis o blood samples om child en wi hin 3 mon hs o 4 yea s o immuniza ion wi h whole cell pe ussis accine e ealed a simila cy okine p o ile, mode - a e o high le els o IFN-, bu unde ec able IL-5. In con as , analysis o cellula esponses o m child en immunized wi h acellula accines demon- s a ed ha p imed T cells sec e ed high le els o IFN-and IL-5 ollowing speci ic an igen s imu- la ion in i o. All o he high e#icacy acellula accines es ed (Smi hKline Beecham 3-componen , Chi on Biocine 3-componen and Connaugh 5-componen ) p oduced his Th0 o mixed Th1/Th2 cy okine p o ile in he majo i y o child en es ed. Access o clinical lo s o pe ussis accines has allowed us o alida e ou mu ine espi a o y challenge model; he a e o bac e ial clea ance ollowing ae osol challenge co ela ed wi h es i- ma es o e#icacy om clinical ials. Fu he mo e, he immune esponses induced in mice we e consis - en wi h ou demons a ion ha acellula and whole cell accines induced dis inc T cell popu- la ions in child en. In mice, he acellula accine induced T cells ha sec e ed IL-5 and IL-4 a e in i o cul u e, bu unde ec able IFN-and low le els o IL-2, a clea Th2 cy okine p o ile, whe eas, he whole cell accine induced a clea Th1 esponse. Recen expe imen s using immunoglobulin, IL-4, o IFN- ecep o gene knockou mice ha e sugges ed ha Th1 esponses a e impo an o bac e ial clea - ance ollowing p ima y in ec ion and in immuni y induced wi h a whole cell accine, whe eas an i- body and Th2 cells play a mo e c i ical ole in he p o ec i e mechanism o he acellula accines. Fu he mo e s a egies ha can shi he immune esponse induced wi h acellula accine om Th2 o Th1, such as he use o an S-1 ecombinan PT mu an o he inclusion o IL-12 in he o mula ion, we e ound o enhance he a e o bac e ial clea - ance ollowing bac e ial challenge. In conclu- sion, ou cu en unde s anding o immuni y o Bo de alla pe ussis sugges s ha an i-Bo de alla pe ussis IgG an ibodies play a key ole in p e en - ing bac e ial adhe ence and ha Bo de alla pe ussis-speci ic T cells (p obably IL-4 and IL-5 sec e ing Th0/Th2 cells) a e equi ed o he induc ion o his humo al esponse, whe eas Th1 cells unc ion in limi ing he cou se o in ec ion h ough enhanced bac e ial up ake and killing by phagocy ic cells. 1045–1056/99/020077+01$30.00/0 1999 The In e na ional Associa ion o Biologicals