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Cell-mediated immune responses in four-year-old children after primary immunization with acellular pertussis vaccines
C M Ausiello1, R Lande, F Urbani
1Departments of Bacteriology and Medical Mycology, Istituto Superiore di Sanità, 00161 Rome, Italy. ausiello@sun.iss.it
Insights
Cell-mediated immunity (CMI) to pertussis antigens wanes by age 4, but new responses emerge, potentially from asymptomatic infections. This may explain continued protection from acellular pertussis vaccines despite declining immune responses.
Area of Science:
- Immunology
- Vaccinology
- Microbiology
Background:
- Acellular pertussis [aP] vaccines induce immune responses, but their durability and impact on cell-mediated immunity [CMI] require further investigation.
- Understanding CMI responses to Bordetella pertussis antigens is crucial for assessing long-term vaccine efficacy.
Purpose of the Study:
- To assess CMI responses to pertussis toxin [PT], pertactin [PRN], and filamentous hemagglutinin [FHA] in children vaccinated with aP vaccines.
- To compare CMI responses at 48 months of age with those at 7 months, after primary immunization.
Main Methods:
- Assessed CMI responses to B. pertussis antigens in 48-month-old children who received aP vaccines.
- Compared CMI responses at 48 months to responses at 7 months (1 month post-primary immunization).
- Monitored antibody [Ab] titers and cytokine profiles (interferon-gamma, interleukin-5).
Main Results:
- Approximately 75% of 4-year-olds showed CMI responses to at least one antigen, similar to 7-month-olds.
- 20-37% of initial CMI responders lost their response by 48 months.
- New CMI responses developed in 36-69% of children who were initially negative, often with stable or rising antibody titers.
- CMI converters showed a type 1 cytokine profile, similar to whole-cell pertussis vaccine responses.
Conclusions:
- Vaccination-induced CMI wanes by age 4, but new responses can be acquired, possibly through asymptomatic B. pertussis infections.
- This acquisition of CMI may contribute to sustained protection against pertussis despite waning vaccine-induced immunity.
- Findings suggest a complex interplay between vaccination, infection, and long-term immunity to pertussis.
Abstract:
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 >/=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.