Division of Immunopathology, Institute for Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, 1090 Vienna, Austria.
Division of Cellular and Molecular Pathophysiology, Institute for Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, 1090 Vienna, Austria.
Int J Mol Sci. 2023 Feb 1;24(3):2725. doi: 10.3390/ijms24032725.
Allergy and rhinovirus (RV) infections are major triggers for rhinitis and asthma, causing a socioeconomic burden. As RVs and allergens may act synergistically to promote airway inflammation, simultaneous treatment strategies for both causative agents would be innovative. We have previously identified the transmembrane glycoprotein intercellular adhesion molecule 1 (ICAM-1) as an anchor for antibody conjugates bispecific for ICAM-1 and (Phl p) 2, a major grass pollen allergen, to block allergen transmigration through the epithelial barrier. Since ICAM-1 is a receptor for the major group RVs, we speculated that our bispecific antibody conjugates may protect against RV infection. Therefore, we created antibody conjugates bispecific for ICAM-1 and the major grass pollen allergen Phl p 5 and analyzed their capacity to affect allergen penetration and RV infection. Bispecific antibody conjugates significantly reduced the trans-epithelial migration of Phl p 5 and thus the basolateral Phl p 5 concentration and allergenic activity as determined by humanized rat basophilic leukemia cells and inhibited RV infection of cultured epithelial cells. A reduction in allergenic activity was obtained only through the prevention of allergen transmigration because the Phl p 5-specific IgG antibody did not block the allergen-IgE interaction. Our results indicate the potential of allergen/ICAM-1-specific antibody conjugates as a topical treatment strategy for allergy and RV infections.
过敏和鼻病毒 (RV) 感染是引发鼻炎和哮喘的主要诱因，造成了巨大的社会经济负担。由于 RV 和过敏原可能协同作用促进气道炎症，因此针对这两种致病因素的同时治疗策略将具有创新性。我们之前发现细胞间黏附分子 1 (ICAM-1) 作为针对 ICAM-1 和 （Phl p）2 的双特异性抗体缀合物的锚点，（Phl p）2 是主要草花粉过敏原，可阻止过敏原穿过上皮屏障迁移。由于 ICAM-1 是主要 RV 群的受体，我们推测我们的双特异性抗体缀合物可能具有预防 RV 感染的作用。因此，我们创建了针对 ICAM-1 和主要草花粉过敏原 Phl p 5 的双特异性抗体缀合物，并分析了它们影响过敏原渗透和 RV 感染的能力。双特异性抗体缀合物显著降低了 Phl p 5 的跨上皮迁移，从而降低了人嗜碱性白血病细胞测定的基底外侧 Phl p 5 浓度和变应原活性，并抑制了培养上皮细胞中的 RV 感染。仅通过预防过敏原迁移才能获得变应原活性的降低，因为 Phl p 5 特异性 IgG 抗体不能阻断过敏原-IgE 相互作用。我们的研究结果表明，过敏原/ICAM-1 特异性抗体缀合物作为过敏和 RV 感染的局部治疗策略具有潜力。
