Case-control Study of the Association Between Pertussis Vaccination in Infancy and the Risk of IgE-mediated Food Allergy

BACKGROUND Atopic diseases have become the most important cause of chronic morbidity among children in wealthy countries. In particular, food allergy, including life-threatening food-related anaphylaxis, is growing at an alarming rate. For example, one Australian allergy clinic observed a 12-fold rise in consultations for food allergy in children between 1995 and 2006. In the 15 years to 2009/10, hospitalisations for food-related anaphylaxis in young Australian children increased more than 8-fold. No effective broadly implementable strategies to curb this 'second wave' of atopic disease have been discovered.

In Australia, an abrupt rise in food allergy coincided closely with the replacement of the antigenically complex whole-cell pertussis vaccine (wP) with the subunit acellular pertussis vaccine (aP) beginning in the late 1990s. Pertussis vaccine protects against Bordatella Pertussis, the causative agent of whooping cough.

Investigators previously shown the marked differences in the immune stimulating profile of wP compared with aP. wP has been shown to induce strong Th1 type immunity while aP induces a Th2 type response. Immune responses can be broadly grouped into cellular (Th1) and antibody mediated immunity (Th2). Natural protective immunity to pertussis relies on strong Th1 type responses to clear the pathogen. This is closely mimicked by the immunity induced by whole cell vaccine (wP). In contrast, the acellular vaccine relies on the development of antibody mediated protection. While antibody mediated responses are protective in the short term, the strong induction of Th2 responses may be deleterious to other aspects of the immune response.

The developing infant immune system has been shown to have a Th2 bias, which may be further skewed by the delivery of a vaccine with a strong Th2 immune profile. Dysregulation of the Th1/Th2 balance which should exist in the immune system can lead to disease states. Predominance of a Th2 environment leads to the development of atopy and allergy. A number of studies, exemplified by those from our centre, detail the Th2 immune bias induced in some infants who received DTaP-only schedules, resulting in excessive IgE production against vaccine antigens. This is likely due to the combined effect of 1) carry-over of the Th2-biased in utero phenotype, 2) the presence of alum and pertussis toxin which have Th2-adjuvantising properties, and 3) the absence of the balancing Th1-stimulating ligands present in DTwP. These effects manifest most strongly in infancy and among children with evidence of an underlying Th2-skewed phenotype.

Studies have demonstrated that the inclusion of even a single wP dose in a pertussis priming schedule is associated with a reduction in Th2-polarised T cell memory and the magnitude of the IgE response compared with a aP-only schedule. Based on these findings it is hypothesised that the inclusion of a single wP dose in the pertussis priming schedule might preserve the Th1/Th2 balance of the developing infant immune system.