Transiently increased IgE responses in infants and pre-schoolers receiving only acellular Diphtheria-Pertussis-Tetanus (DTaP) vaccines compared to those initially receiving at least one dose of cellular vaccine (DTwP) - Immunological curiosity or canary in the mine?

Background: Several previous studies have highlighted the strong Th2-polarising and IgE-promoting activity of the DTaP vaccine, but there is no evidence that this has pathological consequences and accordingly there is no current interest amongst vaccine developers in reformulating DTaP to attenuate these properties. In light of an apparent resurgence in pertussis in many countries, and emerging evidence from other areas of paediatric immunology of IgE-mediated interference with host defence mechanisms, this issue requires more detailed clarification.

Methods: We have re-evaluated the impact of DTaP-only versus mixed DTwP/DTaP vaccination on Th2-dependent "bystander" IgE responses in three cohorts of children under different priming conditions, encompassing both vaccine-targeted and unrelated antigens including food allergens.

Asthma is associated with multiple alterations in anti-viral innate signalling pathways.

Background: Human rhinovirus (HRV) infection is a major trigger for asthma exacerbations. Anti-viral immunity appears to be abnormal in asthma, with immune dysfunction reported in both airway structural cells and migratory, bone marrow derived cells. Though decreased capacity to produce anti-viral interferons (IFNs) has been reported in asthma, a detailed analysis of the molecular events involved has not been undertaken.

Antibody and cell-mediated immunity to pertussis 4 years after monovalent acellular pertussis vaccine at birth.

Background: In a previous study, we found that monovalent acellular pertussis (aP) vaccine at birth and 1 month achieves higher IgG antibody (Ab) levels to pertussis toxoid (PT), filamentous hemagglutinin (FHA) and pertactin by 8 weeks, when compared with controls. Here, we report antibody and cell-mediated immune responses to 4 years of age.

Methods: IgG Ab to PT, filamentous hemagglutinin and pertactin, diphtheria (D) and tetanus (T) was measured in the 3 groups (aP vaccine at birth and 1 month, aP birth only and no aP) at 2 years of age and before and after DTaP-inactivated polio vaccine (DTaP-IPV) at 4 years of age.

Impact of sex steroid ablation on viral, tumour and vaccine responses in aged mice.

Recent evidence suggests that the decline in resistance to viral infections with age occurs predominantly as a result of a gradual loss of naïve antigen-specific T cells. As such, restoration of the naïve T cell repertoire to levels seen in young healthy adults may improve defence against infection in the aged. We have previously shown that sex steroid ablation (SSA) rejuvenates the ageing thymus and increases thymic export of naïve T cells, but it remains unclear whether T cell responses are improved.

Innate interferons inhibit allergen and microbial specific T(H)2 responses.

Several studies provided evidence of innate interferons (IFNs) regulating T(H)2 cytokine production using purified CD4(+) memory cells and T(H)2 polarisation via interleukin-4 (IL-4). Vitally, none of these previous studies examined IFN attenuation of T(H)2 responses to allergen or antigen. This study therefore sought to investigate the abrogation of specific allergen- and antigen-stimulated T(H)2 response in peripheral blood mononuclear cells (PBMC) derived from 12 sensitised individuals by IFN-β and IFN-λ.

Innate IFNs and plasmacytoid dendritic cells constrain Th2 cytokine responses to rhinovirus: a regulatory mechanism with relevance to asthma.

Human rhinoviruses (RV) cause only minor illness in healthy individuals, but can have deleterious consequences in people with asthma. This study sought to examine normal homeostatic mechanisms regulating adaptive immunity to RV in healthy humans, focusing on effects of IFN-αβ and plasmacytoid dendritic cells (pDC) on Th2 immune responses. PBMC were isolated from 27 healthy individuals and cultured with RV16 for up to 5 d.

A genomics-based approach to assessment of vaccine safety and immunogenicity in children.

Immune responses to vaccines in infants and young children are typically Th2-biased, giving rise to concerns regarding potential atopy-like side effects, and antagonism of Th1-associated sterilising immunity. Conventional immunological methodology has limited capacity to effectively address these problems because of the inherent complexity of the immune responses involved. In the present study, we sought to develop an unbiased systems biology approach to elucidate superficially similar Th2-associated responses to paediatric vaccines and allergens, and to differentiate between them via gene coexpression network analysis.

Th2-polarisation of cellular immune memory to neonatal pertussis vaccination.

Current infant vaccination against pertussis in North America and Australia requires three doses of vaccines including diphtheria, tetanus and acellular pertussis antigens (DTaP) at 2, 4 and 6 months of age. Interest is growing in the possibility that vaccination at birth might provide earlier protection of infants, but early vaccination also gives rise to concerns over the potential for excessive Th2-polarisation of pertussis-specific T-cell memory profiles. We evaluated this issue as part of a small pilot study comparing infants receiving a monovalent acellular pertussis vaccine (aP) at birth or birth and at 1 month, followed by DTaP at 2, 4 and 6 months with infants receiving DTaP only from 2 months.

Airway hyperresponsiveness is associated with activated CD4+ T cells in the airways.

It is widely accepted that atopic asthma depends on an allergic response in the airway, yet the immune mechanisms that underlie the development of airway hyperresponsiveness (AHR) are poorly understood. Mouse models of asthma have been developed to study the pathobiology of this disease, but there is considerable strain variation in the induction of allergic disease and AHR. The aim of this study was to compare the development of AHR in BALB/c, 129/Sv, and C57BL/6 mice after sensitization and challenge with ovalbumin (OVA).