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Immune response modulation by recombinant peptides expressed in virus-like particles
E V Svirshchevskaya1, L Alekseeva, A Marchenko
1Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, RAS, Moscow, Russia. esvir@mail.ibch.ru
Abstract:
Aspergillus fumigatus, a ubiquitous fungus, is implicated in the pathogenesis of a number of clinically different allergic diseases in man, including allergic bronchopulmonary aspergillosis. Peptide-based immunotherapy may offer an alternative treatment strategy for the management of allergic disease. The objective of this study was to alter the allergen-specific immune response using dominant T cell epitopes of a major A. fumigatus allergen, Asp f2, expressed in yeast as virus-like particles (VLP). The T cell epitopes of Asp f2, recognized in mice with an H-2d background, were determined by producing T-cell hybridomas. Two dominant T cell epitopes, aa60--71 and aa235--249, were identified and expressed in a yeast VLP system. To induce tolerance VLP-peptides were injected subcutaneously into mice previously immunized with recombinant Asp f2. The T cell immune response was abrogated totally in 3 weeks following a single injection of VLP but was restored 2 months later following intranasal antigen exposure. T-cell depletion resulted in the reduction of 20-30% of all antigen-specific immunoglobulin classes. Thus, recombinant peptides expressed in the VLP system can be used successfully in the modulation of Asp f2-induced immune response in mice, although a single administration is not sufficient to maintain a state of tolerance for a long period of time.
Insights
Peptide immunotherapy using Aspergillus fumigatus (Asp f2) allergen fragments displayed on virus-like particles (VLPs) can modulate allergic immune responses in mice. A single VLP injection temporarily suppressed T cell responses, but tolerance waned over time.
Area of Science:
- Immunology
- Allergology
- Mycology
Background:
- Aspergillus fumigatus is a common fungus linked to allergic diseases like allergic bronchopulmonary aspergillosis.
- Peptide-based immunotherapy presents a potential treatment for managing allergic conditions.
Purpose of the Study:
- To investigate the potential of altering allergen-specific immune responses using dominant T cell epitopes of Aspergillus fumigatus allergen Asp f2.
- To express these epitopes on yeast-derived virus-like particles (VLPs) for immunotherapy.
Main Methods:
- Identified dominant T cell epitopes (aa60--71 and aa235--249) of Asp f2 in H-2d mice using T-cell hybridomas.
- Expressed identified epitopes on yeast VLPs.
- Administered VLP-peptides subcutaneously to mice previously immunized with Asp f2 to induce tolerance.
- Assessed T cell immune response and immunoglobulin levels.
Main Results:
- A single subcutaneous injection of VLP-peptides completely abrogated the T cell immune response within 3 weeks.
- The suppressed T cell response was restored 2 months later after intranasal antigen exposure.
- T-cell depletion led to a 20-30% reduction in antigen-specific immunoglobulin classes.
Conclusions:
- Recombinant peptides expressed on VLPs can successfully modulate Asp f2-induced immune responses in a mouse model.
- A single administration of VLP-peptide immunotherapy is insufficient for long-term tolerance induction.