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  • Similar as the rRBD protein of SARS CoV

    2018-10-25

    Similar as the rRBD protein of SARS-CoV which induced high titres of protective anti-RBD antibody responses in NHPs (Wang et al., 2012), the rRBD vaccination of MERS-CoV induced effective IgG and neutralisation glucocorticoid receptor in our rhesus macaque model. Besides, the induced IgG and neutralisation antibodies maintained for at least 17weeks without obvious attenuation. Following a subsequent boost, antibody titres reached almost their previous peak level. There was no evident difference for induction of the humoral immunity between high and low dose groups. However, high-dose vaccination induced a stronger T-cell response than the low-dose vaccination. Following MERS-CoV challenge, rhesus macaques exhibited a transient glucocorticoid receptor lower respiratory tract infection, in accordance with previous reports (de Wit et al., 2013a,b; Munster et al., 2013; Yao et al., 2013). Although infection was also detected in rRBD-immunised animals, clinical signs were alleviated. Pathological changes in the lungs and tracheas of rRBD-immunised animals indicated reduced, but not fully absent lesions. Using qRT-PCR assay, viral loads in the lungs, trachea and oropharyngeal swabs of the rRBD vaccination groups were decreased. Furthermore, rRBD-immunised monkeys could not isolate MERS-CoV from the lungs while viral loads in the lungs and trachea of mock monkeys were as high as 50 and 100TCID50/mL, respectively. Consistent with the results of immunity elicited by high and low dose of rRBD vaccine, the protection against MERS-CoV infection in monkey could be contributed to the humoral immune especially the neutralising antibodies rather than the cellular mediated immunity. 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 6.5×107 TCID50, 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.
    Competing Interests
    Author Contributions
    Acknowledgements
    Introduction Neisseria meningitidis is a major global cause of meningitis and sepsis with large variations in disease incidence rates and strain distribution globally (Halperin et al., 2012). Incidence rates range from 0.5–15 cases per 100,000 population across most global regions. Very high incidence rates of 100–1000 per 100,000 are witnessed during occasional epidemics across 21 countries (Multi-Disease Surveillance Centre Ouagadougou RMS, 2002–2015) in Africa collectively referred to as the ‘meningitis belt’(Lapeyssonnie, 1968). Meningococci are classified into serogroups based on biochemical properties of their polysaccharide capsule — the primary determinant of meningococcal virulence and major vaccine target. Serogroups A, B, C, W (formerly W-135) and Y cause almost all invasive disease cases. Other virulence determinants are lipooligosaccharide and several outer membrane proteins (Stephens, 2009). Multilocus sequence typing (MLST) (Maiden et al., 1998), based on DNA sequence of seven housekeeping genes, is used to classify meningococci into lineages (sequence types, ST). Closely related STs are termed ‘clonal complex.’