MERS Vaccine Candidate Offers Promise, but Questions Remain

Middle East respiratory syndrome coronavirus (MERS-CoV), a novel human virus that emerged in 2012, has caused significant respiratory disease and kindled fears of a SARS-like epidemic traversing the world (Hilgenfeld and Peiris, 2013). While lacking the rapid human-to-human spread seen with its SARS-CoV cousin, the outbreak of MERS-CoV has continued in the Middle East over the past three years and has lead to infection in 26 countries, N 1500 cases, and N550 deaths (WHO, 2015). With periodic reintroduction from zoonotic sources and the possibility for further human adaptation, MERS-CoV remains a significant global public health threat and highlights the need for therapeutic countermeasures to limit infection and spread. Despite several years of study, understanding of MERS-CoV infection has been limited by a variety of factors including difficulty accessing samples, limited autopsy data, and the lack of robust animal models of disease (Zumla et al., 2015). However, a number of reports have provided both insights and tools for further study including extensive se-quencing data, reverse genetic resources, and monoclonal antibodies for treatment of infection (Zumla et al., 2015). In contrast, vaccine strategies have been limited due to the absence of robust animal models. Typically examined in mice, the presence of specific charge and glyco-sylation difference between human and rodent DPP4, the receptor for MERS-CoV, prevent infection (Peck et al., 2015). Therefore, the traditional approaches to study pathogenesis and vaccine efficacy have been stunted. The lack of a small animal model has shifted MERS-CoV research into larger in vivo models including non-human primates and ungulates (van Doremalen and Munster, 2015). Koch's postulates EBioMedicine 2 (2015) 1292–1293 were first achieved for MERS-CoV in rhesus macaques (Falzarano et al., 2014). Subsequently, other large animal models have been reported including marmosets, camels, rabbits, and alpacas and vary in their levels of MERS-CoV pathogenesis (van Doremalen and Munster, 2015). While new small animal models have been described and continue to be developed, in the short term, non-human primates provide the best model for testing vaccines and therapeutics. In these issues of EBioMedicine, Lan and colleagues describe vaccine studies in a non-human primate model of MERS-CoV infection (Lan et al., 2015). Building on previous studies in rhesus macaques with SARS-CoV (Wang et al., 2012), the report details the efficacy of a MERS vaccine based on a recombinant receptor binding domain (RBD) subunit. Their results indicate stimulation of both humoral and cellular immunity following vaccination and boost. Subsequent …