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