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Infection and Immunity, August 1999, p. 4064-4071, Vol. 67, No. 8
Departments of Bacteriology and Medical
Mycology1 and of Epidemiology and
Biostatistics,2 Istituto Superiore di
Sanità, 00161 Rome, Italy
Received 19 January 1999/Returned for modification 12 February
1999/Accepted 17 May 1999
Cell-mediated immune (CMI) responses to Bordetella
pertussis antigens (pertussis toxin [PT], pertactin [PRN],
and filamentous hemagglutinin [FHA]) were assessed in 48-month-old
recipients of acellular pertussis [aP] vaccines (either from
Chiron-Biocine [aP-CB] or from SmithKline Beecham [aP-SB]) and
compared to CMI responses to the same antigens at 7 months of age,
i.e., 1 month after completion of the primary immunization cycle.
None of the children enrolled in this study received any booster of
pertussis vaccines or was affected by pertussis during the whole
follow-up period. Overall, around 75% of 4-year-old children showed a
CMI-positive response to at least one B. pertussis antigen,
independently of the type of aP vaccine received, and the proportion of
CMI responders were at least equal at 48 and 7 months of age. However,
longitudinal examination of individual responses showed that from 20 (against PT) to 37% (against FHA) of CMI responders after primary
immunization became negative at 48 months of age. This loss was more
than compensated for by conversion to positive CMI responses, ranging
from 36% against FHA to 69% against PRN, in other children who were
CMI negative at 7 months of age. In 60 to 80% of these CMI converters, a lack of decline or even marked elevation of antibody (Ab) titers against B. pertussis antigens also occurred between 20 and
48 months of age. In particular, the frequency of seropositivity to PRN
and FHA (but not to PT) was roughly three times higher in CMI
converters than in nonconverters. The acquisition of CMI response to
B. pertussis antigens in 48-month-old children was not
associated with a greater frequency of coughing episodes lasting
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Copyright © 1999, American Society for Microbiology. All rights reserved.
Cell-Mediated Immune Responses in Four-Year-Old Children after
Primary Immunization with Acellular Pertussis Vaccines
7
days and was characterized by a prevalent type 1 cytokine profile, with
high gamma interferon and low or no production of interleukin-5, reminiscent of cytokine patterns following immunization with whole-cell pertussis vaccine or natural infection. Our data imply that
vaccination-induced systemic CMI may wane by 4 years of age but may be
acquired or naturally boosted by symptomless or minor clinical
infection by B. pertussis. This might explain, at least in
part, the persistence of protection against typical pertussis in aP
vaccine recipients despite a substantial waning of both Ab and CMI
responses induced by the primary immunization.
*
Corresponding author. Mailing address: Department of
Bacteriology and Medical Mycology, Istituto Superiore di Sanità,
Viale Regina Elena, 299, 00161 Rome, Italy. Phone: 39-06-49902890. Fax: 39-06-49387112. E-mail: ausiello{at}sun.iss.it.
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