Recombinant Hypoallergenic Cat Allergy Vaccines
Trifonova D. Curin M. Focke-Tejkl M. Liu Z. Borochova K. Gattinger P. van Hage M. Grönlund H. Kiss R. Huang H.-J. Keller W. Riabova K. Karsonova A. Kundi M. Tulaeva I. Fomina D. Karaulov A. Valenta R.
September 2025John Wiley and Sons Inc
Allergy: European Journal of Allergy and Clinical Immunology
2025#80Issue 92622 - 2635 pp.
Background: Molecular forms of allergen-specific immunotherapy (AIT) for cat allergy are needed. Fel d 1, Fel d 4, and Fel d 7 are the most important cat allergens. Methods: IgE epitopes of Fel d 4 and Fel d 7 were mapped by blocking allergic patients IgE binding with allergen peptide-specific antisera. Five recombinant fusion proteins (PreS-Cat 1-PreS-Cat 5) each containing hepatitis B virus (HBV)-derived PreS as an immunological carrier and non-allergenic peptides from the IgE binding sites of Fel d 1, Fel d 4, and Fel d 7 were expressed in Escherichia coli, purified, and characterized by mass spectrometry, circular dichroism (CD), and size exclusion chromatography. ImmunoCAP and basophil activation experiments demonstrated the hypoallergenic activity of PreS-Cat 1–5. The ability of PreS-Cat 1–5 to induce IgE-blocking antibodies in rabbits was compared to three licensed allergen extract-based AIT vaccines. PreS-Cat 1-5-specific IgG antibodies were tested for inhibition of allergen-specific IgE binding and specific basophil activation. T cell activation and induction of specific cytokine secretion by PreS-Cat proteins were compared with cat allergens in PBMC cultures. Results: Recombinant hypoallergenic, biochemically and structurally defined PreS-Cat 1–5 were obtained. Two subcutaneous immunizations of rabbits with PreS-Cat 1–5 induced equal (Fel d 1) or better (Fel d 4 and Fel d 7) antibodies (PreS-Cat 5 > PreS-Cat 1 > PreS-Cat 3) blocking allergic patients IgE binding to cat allergens than six to fifteen immunizations with allergen extract-based vaccines. PreS-Cat-specific antibodies strongly inhibited specific basophil activation. PreS-Cat 5 > PreS-Cat 1 induced significantly more IL-10 in cultured PBMCs from cat allergic patients than cat allergens. Conclusions: PreS-Cat 5 and PreS-Cat 1 are highly promising molecular vaccine candidates for AIT of cat allergy, combining Fel d 1-, Fel d 4-, and Fel d 7-peptides in single PreS fusion proteins.
allergen , allergen-specific immunotherapy (AIT) , allergy , cat allergy , molecular allergy vaccine
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Department of Pathophysiology and Allergy Research, Division of Immunopathology, Center for Pathophysiology, Infectiology, and Immunology, Medical University of Vienna, Vienna, Austria
LIFE Improvement by Future Technologies (LIFT) Center, Skolkovo, Moscow, Russian Federation
Department of Medicine Solna, Division of Immunology and Respiratory Medicine and Center for Molecular Medicine, Karolinska Institutet and University Hospital, Stockholm, Sweden
Therapeutic Immune Design Unit, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden
Center for Molecular Allergology, Karl Landsteiner University for Healthcare Sciences, Krems, Austria
Institute of Molecular Biosciences, BioTechMed Graz, University of Graz, Graz, Austria
Laboratory of Immunopathology, Department of Clinical Immunology and Allergy, Sechenov First Moscow State Medical University, Moscow, Russian Federation
Department of Environmental Health, Center for Public Health, Medical University of Vienna, Vienna, Austria
Moscow Clinical and Research Center of Allergy and Immunology, Clinical City Hospital #52, Moscow, Russian Federation
Department of Pulmonology, Astana Medical University, Astana, Kazakhstan
Department of Pathophysiology and Allergy Research
LIFE Improvement by Future Technologies (LIFT) Center
Department of Medicine Solna
Therapeutic Immune Design Unit
Center for Molecular Allergology
Institute of Molecular Biosciences
Laboratory of Immunopathology
Department of Environmental Health
Moscow Clinical and Research Center of Allergy and Immunology
Department of Pulmonology
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