Prophylactic Effect of Monoclonal Antibody 1D2 Administration in a Mouse Model of Invasive Aspergillosis

Objective: To investigate the prophylactic efficacy of monoclonal antibody (mAb) 1D2 against Aspergillus fumigatus in an immunosuppressed mouse model of invasive aspergillosis (IA). Methods: BALB/c mice (n = 18) were immunosuppressed with cyclophosphamide and randomly assigned into three groups (n = 6 each): 1D2 prophylaxis, isotype antibody (6B10) control and PBS control. Two hours prior to intravenous inoculation of A. fumigatus conidia (2 × 105 conidia per mouse), 1D2 (100 μg) or control interventions were administered intravenously. Clinical signs and body weight were monitored, and mice were euthanised for tissue and blood collection 48 h after infection. Liver injury was assessed histologically using a modified semi-quantitative scoring system. Fungal burden was assessed by colony-forming unit (CFU) counts in blood and sampled liver, spleen, kidney, and lung tissues. Plasma cytokine concentrations were analysed by ELISA. Results: 1D2-treated mice showed a lower loss of body weight post-inoculation than PBS controls (p = 0.007) and had significantly reduced clinical distress scores on days 1 and 2 (p < 0.05). Histopathological analysis showed alleviated liver injury in the 1D2 group, with a median liver injury score of 4.5 (IQR 3.0–5.25) versus 8.0 (IQR 6.75–10.0) in PBS controls (p < 0.05). CFU counts in the liver, spleen and kidney were significantly lower in the 1D2-treated group than in either control group (p < 0.05). Plasma IL-6 levels were reduced in the 1D2-treated group (582.9 ± 279.7 pg/mL) compared with PBS (1073 ± 289.1 pg/mL) and 6B10 (1080 ± 357.4 pg/mL)-treated controls (p < 0.05). TNF-α and IL-1 showed no significant differences. Conclusions: Prophylactic administration of mAb 1D2 was associated with reduced post-inoculation weight loss, lower clinical distress scores, less liver injury, and reduced recoverable CFU counts in sampled liver, spleen and kidney tissues. Plasma IL-6 concentrations were also lower in the 1D2-treated group. These findings provide proof-of-concept evidence supporting further preclinical evaluation of 1D2 as a prophylactic candidate against IA.