Booster immunization of children with an acellular pertussis vaccine enhances Th2 cytokine production and serum IgE responses against pertussis toxin but not against common allergens

Abstract

SUMMARYAcellular pertussis vaccines (Pa) protect against severe pertussis in children. However, serum antibody responses decline quickly after immunization. Studies in animal models suggest that cell-mediated immunity also contributes to protection against Bordetella pertussis, and it has already been demonstrated that Pa induce T cells that secrete type-1 and type-2 cytokines in children. In this study we examined the persistence of the T cell response and the effect of booster immunization in 4±6-yearold children. Cell-mediated immunity to B. pertussis antigens was detected in a high proportion of children more than 42 months after their last immunization. Peripheral blood mononuclear cells (PBMC) from the majority of children secreted interferon-gamma (IFN-g) and a smaller proportion IL-5, in response to specific antigen stimulation in vitro. However, following booster immunization, significantly higher concentrations of IL-5, but not IFN-g , were produced by PBMC in response to B. pertussis antigens. Furthermore, plasma IL-4 and IL-5 concentrations were increased, whereas IFN-g concentrations were reduced following booster immunization. It has been suggested that childhood immunization with Th2-inducing vaccines may predispose some children to atopic disease. Although we found that pertussis toxin (PT)-specific IgE was significantly increased after booster immunization in both atopic and non-atopic children, the levels of IgE to common allergens and the prevalence of positive skin prick test were unaffected by the booster vaccination. Thus, despite the enhancement of type-2 responses to B. pertussis antigens, booster vaccination with Pa does not appear to be a risk factor for allergy.

Acellular Pertussis Vaccine Protects against Exacerbation of Allergic Asthma Due toBordetella pertussisin a Murine Model

“…In the present study we show that Pa immunization did not enhance the OVA-specific IgE response (Fig. 2B); this suggests that Pa-like vaccines are unlikely to promote atopy and is consistent with the findings of studies of Paimmunized children, which found no significant enhancement of IgE specific to third-party antigens (50). Significantly decreased levels of OVA-specific IgE were observed in mice in group PaBpOVA compared to those in either the PaOVA or the OVA group (Fig.…”

“…Although OVA-induced sensitization does not impair vaccine-mediated clearance of B. pertussis, it was possible that Pa influenced allergic sensitization. An increase in the concentrations of IgE antibodies specific for PT, a component of Pa, has been reported in other studies (40,50). Therefore, the serum IgE responses of mice sensitized to OVA following Pa or sham immunization were examined.…”

“…One contentious interpretation of that study is that vaccine components may be responsible for a portion of the increased prevalence of asthma and allergies in U.S. children. However, a large number of previous studies have demonstrated that Pa protects against the devastating and sometimes fatal childhood disease whooping cough (27,44,50,54) and that current commercial formulations of Pa show greatly reduced reactogenicities compared to that of Pw (6). The latter data unequivocally demonstrate the benefit of Pa immunization to health and justify the selection of Pa for mass vaccination protocols.…”

“…Both Pa immunization and OVA sensitization induce powerful Th2 responses in mice (15,27,50), whereas B. pertussis infection induces strong Th1 responses in mice and children (37,52). The goal of this study was to examine the possibility that Pa immunization enhances allergic sensitization; however, it was also necessary to examine the confounding influence of sensitizing antigen upon clearance.…”

“…Active PT enhances IgE responses to foreign antigens and is widely used as an adjuvant in animal experiments to enhance the immune responses to coadministered antigens (26,51). Inactivated PT is a component of most Pas, and it is known that booster immunization of children with an acellular pertussis vaccine enhanced Th2 cytokine production and serum IgE responses against PT (50). Circulating IgE antibodies against PT have also been found after primary immunization with Pa with or without a subsequent Pa or Pw booster (11,17,42).…”