AIFA Early Career and New Researcher Grant

Dr Isabelle Bosi

Garvan Institute of Medical Research, Children’s Hospital Westmead and Royal Prince Alfred Hospital, Sydney

Research Team: A/Prof Owen Siggs, A/Prof Elissa Deenick, JOnathan Nguyen (Garvan Institute of Medical Research), Prof Bruce Bennetts, Dr Enzo Ranieri, Dr Melanie Wong (Children’s Hospital Westmead) A/Prof Paul Gray (Sydney Children’s Hospital), Dr Kahn Preece (John Hunter Hospital, Newcastle), A/Prof Stephen Adelstein (Royal Prince Alfred Hospital), Dr Joanne Smart (Royal Children's Hospital, Melbourne), Dr Natasha Moseley (Perth Children’s Hospital), A/Prof Jane Peake (Queensland Children's Hospital), Dr Jovanka King (The Women’s and Children’s Hospital, Adelaide)

Primary immune deficiencies (PID), also known as Inborn errors of immunity (IEI) are a group of genetic conditions that affect the function of a person's immune system. This may cause infections and/or abnormal immune activity. Severe Combined Immunodeficiency (SCID) is a sub-group of IEI that cause abnormal development of essential immune cells. SCID is fatal without treatment and early detection improves survival.

A newborn screening test for SCID is now offered to all newborns in Australia. This involves collecting blood from a heel prick onto card and testing for normal byproducts of immune cell development (TRECs and, in some states, KRECs). The current test is very useful, but it cannot pick up all children with SCID or IEI. The test also cannot diagnose the sub-type of SCID, which is important for choosing the best treatment.

This project will investigate whether routine genetic testing (whole genome sequencing or WGS) performed on newborn screening cards can improve the diagnosis of SCID and other IEIs. WGS may be useful as an upfront test or after abnormal TREC and/or KREC levels are identified.

This study has 3 main aims. Firstly, the team will perform whole genome sequencing on the NBS cards of individuals with diagnosed IEI, to see if they can pick up their diagnosis using WGS alone. Next, they will perform WGS on the NBS cards of newborns with an abnormal TREC/KREC result. They will explore whether a fast, accurate diagnosis can be made with WGS alone. Finally, the researchers will study whether new tests can be developed that may be helpful for diagnosing IEI as a newborn.

The team hopes that this study will improve the diagnosis of IEI and allow earlier access to treatment.

AIFA Early Career and New Researcher Grant

Dr Etienne Masle-Farquhar

Garvan Institute of Medical Research, Sydney

Research Team: Prof Russell Dale, Dr Melanie Wong, Dr Shruti Swarmy, Dr Jacinta Perram, Dr Katherine Jackson, Prof Susan Clark, Dr Timothy Peters, Christopher Jara, Caitlin Bartie (Garven Institute of Medical Research), Dr Yogesh Jeelall (Sir Charles Gairdner Hospital, Perth)

The goal of this project is to understand how mutations within B lymphocytes, that modify a gene called KMT2D, cause autoimmune disease and/or immune deficiency in young children with Kabuki Syndrome (KS) or in adults with a rare anemia called Cold Agglutinin Disease (CAD). In addition to KS and CAD, mutations in KMT2D are incredibly frequent in up to 30% of B cell non-Hodgkin lymphomas, which are often life-threatening diseases.

By identifying cohorts of patients with these diseases, and using cutting-edge immunology and sequencing methods to identify and study specific “Rogue” B cells harbouring KMT2D mutations, the team hopes to aid in the diagnosis, monitoring and eventually treatment of individuals with KS and CAD.  Their findings will also have broad relevance to scientists and clinicians studying or treating B cell lymphomas.

AIFA Early Career and New Researcher Grant

Dr Shaymaviswanathan Karnaneedi

James Cook University, Townsville

Research Team: Prof Andreas Lopata (James Cook University), Prof Sheryl van Nunen OAM (The University of Sydney), A/Prof Graham Mackay (The University of Melbourne)

Due to global resource constraints and climate change mitigation putting limits on traditional animal-derived protein production, complementary proteins from insects have become a great alternative sustainable food source to feed the growing population due to their high protein and nutrient content and low greenhouse gas production during rearing. The Food Standards Australia New Zealand’s Advisory Committee for Novel Foods (FSANZ-ACNF) have assessed and declared crickets and mealworms as safe for human consumption and are currently available in the Australian health food and fitness supplement market.

Due to ancestral similarities between insects and shellfish, and house dust mites (HDM), edible insect-derived proteins can be unsafe and harmful when consumed by people who are allergic to shellfish and HDM. Australia has a high prevalence of shellfish food allergy as well as house dust mite allergy, however, no studies have demonstrated the level of risk faced by consumers with these allergies when consuming edible insects.

The diagnostic capacity for edible insects in Australia is also severely underdeveloped. The food allergy research group at James Cook University has been investigating edible insect-based food proteins, particularly for crickets and mealworms and has shown strong laboratory-based evidence of cross-allergy of shellfish- and HDM-allergic individuals to crickets and mealworms.

In this study, the team plan to first isolate the proteins from crickets and mealworms that can cause cross-allergy in shellfish- and HDM-allergic individuals. Following this, to demonstrate true clinical allergy, they plan to study the capacity of two diagnostic methods that utilise immune cells that mimic clinical allergy in shellfish- and HDM-allergic individuals. These methods, known as the “basophil activation test” (BAT) and “mast cell activation test” (MAT), have the potential to accurately diagnose edible insect food allergy without the need for subsequent skin prick tests (SPT) or oral food challenge (OFC).

AIFA Early Career and New Researcher Grant  

Ms Kayla Parker

Murdoch Children’s Research Institute (MCRI), Melbourne

Research Team: Prof Kirsten Perrett, A/Prof Rachel Peters, Dr Vicki McWilliam, Dr Victoria Soriano, Ms Audrey Walsh (MCRI)

Tree nut allergies are frequently life-long and severe as the accidental ingestion of tree nuts can risk life-threatening reactions involving IgE antibodies. Tree nut allergies are also common, affecting 3% of Australian children. Infants with a peanut allergy are at a higher risk of a tree nut allergy, with 40% developing a tree nut allergy by school-age.

Tree nut allergy can be a clinical and diagnostic challenge. Due to the increased risk of developing multi-nut allergies, infants with a peanut allergy often undergo tree nut IgE screening tests before introducing tree nuts into the diet to assess their risk of tree nut allergy. Positive screening results will often guide advice for strict tree nut avoidance until a diagnostic oral food challenge test (OFC). With ever-growing OFC waiting lists in an already overwhelmed healthcare system, this makes conducting potentially multiple individual tree nut OFCs nonviable to determine an infant’s allergy profile. Additionally, there is a lack of evidence to support this approach with international guidelines recommending against pre-ingestion screening. The delayed introduction, or complete avoidance, of tree nuts whilst waiting for an OFC may further increase the risk of developing a tree nut allergy.

This project will involve infants from the TreEat study, a randomised control trial investigating the safety and efficacy of early tree nut ingestion in preventing tree nut allergy in infants with a peanut allergy. Infants with a blood sample (n=125) taken before tree nuts were ever ingested (age 4 to 11 months) and at follow-up (age 18 months) will be included. Their blood IgE levels to cashew, hazelnut, walnut and almond will be measured pre- and post-ingestion, and their tree nut ingestion history and allergy outcomes at follow-up will be determined.

This research will provide world-first evidence on whether the early introduction of tree nuts can modify the association between tree nut IgE levels and allergy development among high-risk infants with peanut allergy. This research will also help inform clinical management by understanding whether infants with peanut allergy can safely introduce tree nuts into their diet irrespective of pre-ingestion screening results.

AIFA DBV Technologies Food Allergy Research Grant 

Dr Tim Brettig

Murdoch Children’s Research Institute (MCRI), Melbourne

Research team: Prof Kirsten Perrett, A/Prof Rachel Peters, Dr Vicki McWilliam (MCRI) 

The 2020 bipartisan Federal Government Inquiry into Allergies and Anaphylaxis recommended the provision of safe and effective treatments for food allergy is a health priority¹. Oral immunotherapy (OIT) is a form of food allergy treatment, shown to improve the outcomes for people living with food allergy².

In Australia, OIT is undergoing translation into clinical practice with the National Allergy Centre of Excellence (NACE) ADAPT OIT Program (ADAPT: from Allergy Development to an Accelerated Pathway to Tolerance) currently being implemented for children under 18 months of age with peanut allergy in several public hospitals.

There is a lack of evidence using randomized controlled trials (RCTs) for evaluation of tree nut OIT, and to date there is only one overseas study describing OIT for multiple simultaneous nut OIT³. Given the progression of peanut OIT as a treatment option in Australia, the LMNOP (low-dose multiple nut oral immunotherapy program) pilot outcomes will provide crucial evidence for feasibility, acceptability, tolerability and compliance of multiple-nut OIT. AIFA funding will support the analysis of these outcomes and, if successful, direct translation and implementation into routine clinical care. As an expansion of the NACE ADAPT OIT Program, Australian infants with multiple-food allergy could then be treated with multiple-nut OIT, enabling the possibility of enhanced life-changing individual benefit and reduced health-care burden.

AIFA acknowledges the support of DBV Technologies for this Food Allergy Research Grant of $15,000

References:

1. Walking the allergy tightrope: addressing the rise of allergies and anaphylaxis in Australia 2020 [2023 Mar 12]. Available from: https://www.aph.gov.au/Parliamentary_Business/Committees/House/Health_Aged_Care_and_Sport/Allergiesandanaphylaxis/Report
2. Epstein-Rigbi N, Goldberg MR, Levy MB, Nachshon L, Elizur A. Quality of Life of Food-Allergic Patients Before, During, and After Oral Immunotherapy. J Allergy Clin Immunol Pract. 2019;7(2):429-36.e2.
3. Erdle SC, Cook VE, Cameron SB, Yeung J, Kapur S, McHenry M, et al. Real-World Safety Analysis of Preschool Tree Nut Oral Immunotherapy. J Allergy Clin Immunol Pract. 2023;11(4):1177-83.

AIFA Professor Ann Kupa Food Allergy Research Grant

Dr Jacqueline Loprete

St Vincent's Hospital, Sydney

Research team: Prof Andrew Carr, Dr Winnie Tong, Ms Robyn Richardson, Mr Jonathan Montemayor, Mr Jamie Rogers, Dr Karran Pathmanandavel (St Vincent’s Hospital)

Peanut is one of the most frequent causes of food allergy in Australia, affecting 1 in 100 adults¹. Peanut allergy also affects approximately 3% of children. Given that only 20% of children will grow out of their peanut allergy², it follows that the proportion of adults living with peanut allergy will only increase over time.

Not only is peanut allergy common, but it caused almost 20% of deaths in adults from food-related anaphylaxis in Australia between 1997 and 2013³. These deaths all occurred in patients with a known allergy to peanut, including patients who previously had anaphylaxis to peanut and carried an adrenaline injector that can abort anaphylaxis. Adults are at greater risk than children of severe reactions to accidental peanut exposure³.

Peanut allergy can also have significant psychosocial impacts. It limits social interactions and increases anxiety in patients and their families⁴. The only recommended treatment for the prevention of peanut allergy in adults is strict avoidance, including of products that are labelled as “may contain traces of peanut”. However, the risk of hidden allergens in packaged products and food prepared outside of the home cannot be discounted⁵. Avoidance is supplemented by carrying an adrenaline injector in case of accidental exposure. This constant need for vigilance is what drives the psychosocial stress for those with a peanut allergy and their loved ones.

One tool available to treat IgE-mediated reactions is immunotherapy. Allergen immunotherapy involves exposing an individual to gradually increasing amounts of the substance to which they are allergic to induce immune tolerance, which allows reactions to become less severe or to disappear completely. With non-food-induced allergy, allergen immunotherapy is proven to be an effective treatment (e.g. immunotherapy for bee venom anaphylaxis is life-saving)⁶ and is the standard of care.

There is limited data regarding food immunotherapy in adults. The PALISADE group demonstrated efficacy in 40% of adults compared to 65% of children⁷. This 40% rate was also lower than in other studies of peanut immunotherapy in children^8-10. A systematic review food immunotherapy studies showed a significant risk reduction in children but not in adults¹¹.

The reason for the lower efficacy in adults compared to children is unclear. The dropout of adults in food immunotherapy studies is higher than children¹², perhaps due to more frequent and more severe adverse reactions¹³. Immunotherapy in children may also be more successful because the younger immune system has more plasticity.

The recently completed Combining Peanut Oral Immunotherapy and Omalizumab in Adults with Peanut Allergy (OPAL) Study was an Australian-first, prospective, single-arm study. It recruited adults who reacted to less than one peanut kernel (300mg of peanut protein). OPAL evaluated the usefulness of omalizumab, a medication targeted against the IgE protein responsible for triggering allergic reactions, plus peanut immunotherapy.

The OPAL study demonstrated comparable and possibly superior efficacy and comparable safety when compared indirectly to previously published studies in adults. However, the OPAL protocol required 14 visits over 6 months, which for most adults translated to 14 days off work. A shorter protocol is essential for these results to be translated into routine clinical practice. We propose a new study with fewer visits (7 vs. 14) over a shorter duration (12 vs. 24 weeks).

The primary aim of this study is to assess if a rapid protocol of omalizumab and peanut immunotherapy has similar efficacy and safety as the established OPAL protocol. The team also aims to assess the incidence and severity of reactions to a peanut challenge after 36 weeks of maintenance oral peanut immunotherapy, the frequency and severity of accidental peanut exposure, changes in quality-of-life markers in people undergoing peanut immunotherapy, changes in immunological markers in individuals undergoing immunotherapy, and to compare these outcomes to the results of the OPAL study.

AIFA acknowledges the support of Professor Ann Kupa for this Food Allergy Research Grant of $20,000

References