Nearly one billion people globally suffer from allergies, representing a considerable social and economic impact, significant morbidity and reduced quality of life. Allergic diseases most commonly develop in infancy, meaning that children are exposed to life-long treatments that can cause considerable and irreversible side effects. Compelling evidence suggests that sensitisation occurs within the first two years of life when the gut microbiome establishes. Over this period, a delicate balance linking the microbiome and the immune system exists, which, if perturbed, results in heightened allergen-specific Th2 responses. These observations imply a “window of susceptibility” for the development of sensitisation that could be explored as an intervention opportunity to prevent atopy.
We have recently described that a hookworm recombinant protein, named Anti-Inflammatory Protein (AIP)-2, is able to suppress allergic responses in both mice (in vivo) and humans (ex vivo), and to promote sustained immune regulation in mice. We have found that AIP-2 administered via breastmilk (BM) within the first week of life, modified the composition of the gut microbiome and protected pups from asthma onset into adulthood. Our central hypothesis is that AIP-2 and BM co-factors prevent sensitisation by modifying the immune and microbiome landscape promoting sustainable tolerance.