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

Although rRBD vaccination alleviated pneumonia and decreased viral load in the rhesus macaque upon challenge with MERS-CoV in this study, it did not prevent the infection of MERS-CoV completely. The data should be interpreted with some cautions. First, the rhesus macaque models to mimic MERS-CoV infection had inevitable limitations. In both the present and previous reports, MERS-CoV challenge in the rhesus macaque models resulted in transient infection of the lower respiratory tract (de Wit et al., 2013a,b; Munster et al., 2013; Yao et al., 2013) and the more severe or even lethal disease course frequently associated with human cases was not observed herein (van den Brand et al., 2015) . Therefore, the prophylactic effects of the rRBD vaccine were not fully demonstrated in this model. Second, MERS-CoV challenge in the trachea bypasses the natural entry sites, such as nasal mucosa and laryngeal areas of the pharynx which show as crucial regions of mucosal immunity (Sato and Kiyono, 2012) , while, the bypassed mucosal immunity is the first defence against lots of infectious diseases, including MERS-CoV (Neutra and K. P., 2006) . Third, the challenge dose of 6.5 × 10 7 TCID 50 , was markedly greater than typical MERS-CoV exposure in humans. More recently, a progressive and lethal pneumonia was observed in a MERS-CoV challenged common marmoset model (Falzarano et al., 2014) , in which the infected animals developed viremia, and total RNA sequencing demonstrated the induction of immune and inflammatory pathways (Falzarano et al., 2014) . Therefore, the marmoset model corresponds closely to the disease course in humans and allows for clearer discrimination between successfully treated and control animals. Therefore, the protective efficacy of this vaccine candidate remains to be tested in a more suitable disease model (e.g. common marmoset) or humans.