Eberlein Valentina, Rosencrantz Sophia, Finkensieper Julia, Besecke Joana Kira, Mansuroglu Yaser, Kamp Jan-Christopher, Lange Franziska, Dressman Jennifer, Schopf Simone, Hesse Christina, Thoma Martin, Fertey Jasmin, Ulbert Sebastian, Grunwald Thomas
Fraunhofer Institute for Cell Therapy and Immunology IZI, Leipzig, Germany.
Fraunhofer Cluster of Excellence Immune-Mediated Diseases (CIMD), Frankfurt am Main, Germany.
Front Immunol. 2024 Apr 5;15:1382318. doi: 10.3389/fimmu.2024.1382318. eCollection 2024.
The respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory tract infections associated with numerous hospitalizations. Recently, intramuscular (i.m.) vaccines against RSV have been approved for elderly and pregnant women. Noninvasive mucosal vaccination, e.g., by inhalation, offers an alternative against respiratory pathogens like RSV. Effective mucosal vaccines induce local immune responses, potentially resulting in the efficient and fast elimination of respiratory viruses after natural infection. To investigate this immune response to an RSV challenge, low-energy electron inactivated RSV (LEEI-RSV) was formulated with phosphatidylcholine-liposomes (PC-LEEI-RSV) or 1,2-dioleoyl-3-trimethylammonium-propane and 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DD-LEEI-RSV) for vaccination of mice intranasally. As controls, LEEI-RSV and formalin-inactivated-RSV (FI-RSV) were used i.m. vaccination. The RSV-specific immunogenicity of the different vaccines and their protective efficacy were analyzed. RSV-specific IgA antibodies and a statistically significant reduction in viral load upon challenge were detected in mucosal DD-LEEI-RSV-vaccinated animals. Alhydrogel-adjuvanted LEEI-RSV i.m. showed a Th2-bias with enhanced IgE, eosinophils, and lung histopathology comparable to FI-RSV. These effects were absent when applying the mucosal vaccines highlighting the potential of DD-LEEI-RSV as an RSV vaccine candidate and the improved performance of this mucosal vaccine candidate.
呼吸道合胞病毒(RSV)是导致急性下呼吸道感染并引发大量住院病例的主要病因。最近,针对RSV的肌肉注射疫苗已被批准用于老年人和孕妇。非侵入性黏膜疫苗接种,例如通过吸入方式,为预防像RSV这样的呼吸道病原体提供了一种替代方法。有效的黏膜疫苗可诱导局部免疫反应,有可能在自然感染后高效快速地清除呼吸道病毒。为了研究对RSV攻击的这种免疫反应,将低能电子灭活RSV(LEEI-RSV)与磷脂酰胆碱脂质体(PC-LEEI-RSV)或1,2-二油酰基-3-三甲基铵丙烷和1,2-二油酰基-sn-甘油-3-磷酸乙醇胺(DD-LEEI-RSV)配制用于小鼠鼻内接种疫苗。作为对照,LEEI-RSV和福尔马林灭活RSV(FI-RSV)用于肌肉注射接种。分析了不同疫苗的RSV特异性免疫原性及其保护效力。在黏膜接种DD-LEEI-RSV的动物中检测到RSV特异性IgA抗体,并且在攻击后病毒载量有统计学上的显著降低。铝佐剂LEEI-RSV肌肉注射显示出Th2偏向,伴有IgE、嗜酸性粒细胞增加以及与FI-RSV相当的肺部组织病理学变化。应用黏膜疫苗时则没有这些效应,突出了DD-LEEI-RSV作为RSV疫苗候选物的潜力以及这种黏膜疫苗候选物的改进性能。