In 2021, Chen and colleagues developed a new IL-17A antibody, also known as humanized rabbit monoclonal antibody HZD37-5 which can reduce the inflammation response in patients with psoriasis, psoriatic arthritis, axial spondyloarthritis and other autoimmune diseases (Chen et al., 2021). Dysregulation of IL-17A was shown to result in pro-inflammatory diseases and thus the treatment is designed to block IL-17A directly or via preventing IL-17A signaling pathways.

          Since human-derived IL-17A antibodies such as Secukinumab and Brodalumab can cause adverse reactions by worsening Crohn’s disease (CD) while neutralizing IL-17A in psoriasis can cause haemorrhagic diarrhoea, HZD37-5 which is derived from rabbits was designed to target N78 loci of IL-17A and reduce the inflammation response by blocking IL-17A transducing signals. Most importantly, HZD37-5 had high affinity and specificity for human and rhesus IL-17A. 

 

          Recently, rabbit-derived therapeutic antibody drug had been widely used when Beovu (the first rabbit-derived scFv monoclonal antibody) had been approved by FDA to treat wet age-related macular degeneration (AMD) (Avaylon, Lee, & Gallemore, 2020) while Vyepti (the world’s second rabbit antibody drug) was used to treat migraine in adults (Morgan & Joyner, 2021). Beovu and Vyepti were used because rabbit antibodies have rich antibody expression profile, higher affinity and easy to humanize.

          The rationale of this study is active IBD in pregnant women was associated with an increased risk of adverse pregnancy outcomes including increased rates of spontaneous abortion, preterm delivery, low birth weight, and severe preeclampsia, as well as increased likelihood of delivery by caesarean (Boyd, Basit, Harpsøe, Wohlfahrt, & Jess, 2015). This study is important to determine the preclinical safety profile of vedolizumab due to the concerns of Vedolizumab may be harmful to pregnant women and their foetuses. 

          The result of this study showed that the administration of high doses of vedolizumab did not show any maternal or developmental effects in rabbits when vedolizumab was shown to be pharmacologically active in rabbits as assessed by target binding saturation. 100 mg/kg of vedolizumab which is the highest dose tested was determined to be the no observed adverse effect level (NOAEL) in rabbits and this dose is approximately 20 times the recommended human dosage. Therefore, vedolizumab is safe to be used as the treatment for IBD even in the pregnant females when no increased risk of congenital abnormalities or adverse pregnancy outcomes can be observed in this study.

          NZW is suitable to be used as animal model to understand pathogenesis and treatment of P. aeruginosa pneumonia because it reflects the human pattern of infection over a 14-day period. These models also allow for serial microbiological, pharmacokinetic, proteomic, and immunological sampling of blood over a 14-day period, thus providing a detailed assessment of dosage, pharmacokinetic or pharmacodynamic relationships and outcome. The persistent neutropenia of NZW model also summarises the host deficits of immunocompromised patients with hematological malignancies (Petraitis et al., 2019). 

          The result showed that C/T can significantly reduce the burden of Pseudomonas aeruginosa in rabbit lung tissue. This study thus established a preclinical foundation for design and implementation of a clinical trial of ceftolozane-tazobactam as the primary treatment for P.aeruginosa bacteremia and pneumonia in immunocompromised patients with profound neutropenia, hematological malignancies, and hematopoietic stem cell transplantation (Petraitis et al., 2019) 

Tracheal intubation is difficult due to the small size of mouth and larynx.

Lungs: 4 right lobes & 2 left lobes.