Cell-mediated immune responses in four-year-old children after primary immunization with acellular pertussis vaccines

Cell-mediated immune (CMI) responses to Bordetella pertussis antigens (pert ussis toxin [PT], pertactin [PRN], and filamentous hemagglutinin [FHA]) wer e 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 chil dren enrolled in this study received any booster of pertussis vaccines or w as 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 c ompensated for by conversion to positive CMI responses, ranging from 36% ag ainst 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 e ven 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 h igher in CMI converters than in nonconverters. The acquisition of CMI respo nse to A: pertussis antigens in 48-month-old children was not associated wi th a greater frequency of coughing episodes lasting greater than or equal t o 7 days and was characterized by a prevalent type 1 cytokine profile, with high gamma interferon and low or no production of interleukin-5, reminisce nt of cytokine patterns following immunization with whole-cell pertussis va ccine or natural infection. Our data imply I-hat vaccination-induced system ic 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 expl ain, at least in part, the persistence of protection against typical pertus sis in aP vaccine recipients despite a substantial waning of both Ab and CM I responses induced by the primary immunization.