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

Considerable evidence has proved that recombinant receptor binding domain (rRBD)-based subunit vaccine is a promising candidate vaccine against the SARS-CoV infection. As rRBD of SARS-CoV Spike protein induced strong neutralisation antibody and long-term protective immunity in rabbits and mice and completely protected immunized mice from SARS-CoV infection . Furthermore, high titres of neutralisation antibodies in non-human primates (NHP) were induced by vaccination with the rRBD of SARS-CoV (Wang et al., 2012) . Experience using rRBD-based subunit vaccines against SARS could inform the design of a rRBD-based MERS vaccine. Several human neutralising antibodies targeting the RBD of the MERS-CoV spike protein, have been identified from the naïve-antibody library Ying et al., 2014) , suggesting that RBD contains epitopes that can induce nAbs and therefore may represent a target antigen against MERS-CoV. Our group and others have confirmed rRBD protein induced strong neutralising antibody responses against MERS-CoV infection in mice and rabbits Lan et al., 2014; Ma et al., 2014; Mou et al., 2013; Zhang et al., 2015) . Although the rRBD subunit vaccine is a highly potent neutraliser of antibodies and T-cell immune responses, no formulation has been tested on a higher animal model with MERS-CoV challenge to verify its prophylactic efficacy (Gretebeck and Subbarao, 2015) . Recently, MERS-CoV infection and disease animal models have been developed (Agrawal et al., 2015; de Wit et al., 2013a,b; Falzarano et al., 2014; Munster et al., 2013; Pascal et al., 2015; Yao et al., 2013; Zhao et al., 2014) , including a rhesus macaque model of naturally permissive MERS-CoV disease (de Wit et al., 2013a,b; Munster et al., 2013; Yao et al., 2013) . We herein evaluate a rRBD subunit vaccine in a rhesus macaque model, to identify a prophylactic approach that could be used in humans to prevent MERS-CoV infection.