MERS Vaccine Candidate Offers Promise, but Questions Remain

摘要: Middle East respiratory syndrome coronavirus (MERS-CoV), a novel human virus that emerged in 2012, has caused significant disease and kindled fears of SARS-like epidemic traversing the world (Hilgenfeld Peiris, 2013). While lacking rapid human-to-human spread seen with its SARS-CoV cousin, outbreak MERS-CoV continued over past three years lead to infection 26 countries, > 1500 cases, > 550 deaths (WHO, 2015). With periodic reintroduction from zoonotic sources possibility for further adaptation, remains global public health threat highlights need therapeutic countermeasures limit spread. Despite several study, understanding been limited by variety factors including difficulty accessing samples, autopsy data, lack robust animal models (Zumla et al., However, number reports have provided both insights tools study extensive sequencing reverse genetic resources, monoclonal antibodies treatment In contrast, vaccine strategies due absence models. Typically examined mice, presence specific charge glycosylation difference between rodent DPP4, receptor MERS-CoV, prevent (Peck Therefore, traditional approaches pathogenesis efficacy stunted. The small model shifted research into larger vivo non-human primates ungulates (van Doremalen Munster, Koch's postulates were first achieved rhesus macaques (Falzarano 2014). Subsequently, other large reported marmosets, camels, rabbits, alpacas vary their levels new described continue be developed, short term, provide best testing vaccines therapeutics. In these issues EBioMedicine, Lan colleagues describe studies primate (Lan Building on previous (Wang 2012), report details MERS based recombinant binding domain (RBD) subunit. Their results indicate stimulation humoral cellular immunity following vaccination boost. Subsequent intra-tracheal challenge vaccinated monkeys revealed partial protection induced reduced pneumonia viral titers. Having tested SARS platform potential as response approach future emergent CoV outbreaks. Similarly, could also deployed reservoir populations like camels are thought harbor this RBD-based failed produce sterilizing typically sought context vaccination. Overall, demonstrate macaque model, subunit target receptor-binding can offer some level protection, but require refinement induce immunity. While shows promise domain-based platforms, questions remain. which supports replication, fails recapitulate severe humans. As such, may underestimate utility or, alternatively, provides only minor disease. Further more pathogenic marmoset or adapted viruses is required decipher question. while drives aspects cannot model. Previous work double inactivated had shown young mice (Spruth 2006); however, subsequent analysis aged animals heterologous failure immune pathology (Bolles 2011). not experimental systems, age immuno-compromised status appears co-morbidity lethality 2013, Zumla any compromised must considered. addition, increases likelihood exposure virus. focus RBD MERS, vaccine-induced reduced; confirm result. Overall, promising MERS-RBD-based development. combination strong neutralization indicates worth pursuing. additional capture humans, populations, challenge. Despite caveats, success important implications well development platforms