Immunomodulatory Capacity and Therapeutic Potential of S.mansoni-Derived Proteins in the Context of Immune Modulation, Asthma and/or Allergy

Summary

During chronic schistosome infections, a complex regulatory network is induced to regulate the host immune system, in which IL-10-producing regulatory B cells (Breg) play a significant role. Schistosomal egg antigens (SEA) are bound and internalized by specific murine B cells and induce both human and mouse IL-10 producing Breg cells. To identify Breg inducing proteins in SEA, HPLC-fractionation was applied, showing some active fractions. Proteomics analysis on several fractions was performed and identified a number of unique proteins of which some were highly abundant. Identification of unique Breg-inducing molecules may form interesting treatment targets for inflammatory diseases such as asthma or allergies.

Background

Current treatment of asthma are mainly bronchodilators or inhaled corticosteroids with or without the long-lasting β2-agonists. Daily use of these medications is required, to prevent recurrence of inflammation and bronchoconstriction. In addition to the high therapy compliance, other disadvantages of the commonly used treatment for asthma are possible long-term side effects and the lack of responsiveness in severe, therapy-resistant asthma patients. Certain environmental and health factors increase risk of wheezing or asthma in children, or the pathology of existing asthma. Additionally, neither cure nor preventional therapy for asthma exists, only medication to alleviate symptoms. Avenues that focus on primary prevention have the potential to open a completely new market. Helminths derived molecules represent an attractive source of new immunomodulatory therapeutics/biologicals for use in asthma (or allergy) treatment.

Technology

Some candidate proteins were identified as potentially immunomodulatory in fractions of parasite material with the capacity to induce IL-10 from mouse B cells. These crude molecules also seem to be able to block type 2 innate cytokines from human primary bronchial epithelial cells. They were therefore recombinantly produced using specific separation techniques. One specific candidate molecule has also
been tested against human B cells, whereby it also shows the capacity to
induce IL-10. In addition, these pure molecules will also be tested in bronchial epithelial cells to evaluate their capacity to block respiratory infections, such as rhinoviruses.

Value Proposition

The global Asthma and COPD Drugs Market Size alone was valued at
$32988.7 million in 2020 and is projected to reach $52049.54 million by
2030, registering a CAGR of 4.64% from 2021 to 2030. Asthma is a noncommunicable, chronic inflammatory lung disorder of the airways
(www.alliedmarketresearch.com).

Team

Prof. Hermelijn H. Smits currently holds the position as Professor in 'Host-commensal interactions and Immunemodulation' at the Parasitology department within the Leiden University Medical Center in
Leiden/ The Netherlands. She worked at this invention together with her
team.