Recombinant Receptor Binding Domain Protein Induces Partial Protective Immunity in Rhesus Macaques Against Middle East Respiratory Syndrome Coronavirus Challenge()

Lan, Jiaming; Yao, Yanfeng; Deng, Yao; Chen, Hong; Lu, Guangwen; Wang, Wen; Bao, Linlin; Deng, Wei; Wei, Qiang; Gao, George F.; Qin, Chuan; Tan, Wenjie

To investigate pneumonia following MERS-CoV infection, histopathological and immunohistochemical analyses were conducted to elucidate the effect of rRBD vaccination. Control monkey lung tissues exhibited moderate lesions (Fig. 4a) with abundant alveolar oedema, fibrin formation in the hyaline member and a small-to-moderate degree of macrophage fibrous infiltration (Fig. 4b) . In contrast, a mild-tomoderate-sized lesion was observed in the lung tissue of rRBDimmunised monkeys (Fig. 4c-f ). Infiltration of inflammatory cells was also detected in the tracheas of mock group monkeys (Fig. 4g) . Although inflammatory cell infiltration and impaired epithelium in the tunica mucosa bronchiorum were also found in the rRBD vaccination group (Fig. 4h-i) , all of the lesion were alleviated compared to the control group. Glomerular capsule expansion was observed in the kidneys of all challenge monkeys (data not shown), but this was considered an incidental, clinically non-significant finding. No specific pathological changes were observed in the spleens of immunised monkeys (data not shown). Viral antigen, using a polyclonal antibody against nucleoprotein, was found by IHC in the lungs (Fig. 5a-c) and tracheas ( Fig. 5d−f) of all monkeys. No specific antigen was detected in the kidneys of challenged monkeys (data not shown). Fig. 3 . Radiographic alterations and lung pathology. a. X-rays from rhesus macaques imaged prior to (−1 day) and post-MERS-CoV inoculation (1 day and 3 days). Areas of interstitial infiltration, indicative of pneumonia, are highlighted (circle). b. Gross pathology of the lungs from necropsied animals at 3 dpi. Haemorrhage and necrosis indicated by the black circle in both high and low dose immunisation groups were small and local, which happened in the mock group were large and disperse. M, H and L represent the mock, high-and lowdose groups, respectively.