5609
Mahmoud Mohamed Mostafa Shehata
Development of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) candidate vaccine
MERS-CoV, surveillance, vaccine, and Egypt
Middle East Respiratory Syndrome Coronavirus (MERS-CoV) represents a global human health threat since its first zoonotic transmission to humans. Since 2012, a total of 2229 human confirmed infections with MERS-CoV were documented (791 fatalities; case-fatality rate=36%) in 27 countries. Herein, an active surveillance of MERS-CoV in Egypt among local and imported camels was conducted to demonstrate the prevalence situation and to characterize MERS-CoVs in Egypt. Subsequently, a well-characterized MERS-CoV isolate was used to develop vaccines via three different approaches; (1) DNA vaccines (encode structural proteins spike S, envelope E, membrane M and nucleocapsid N); (2) outer-membrane vesicles (OMVs)-based preparations expressing receptor-binding domain (RBD) of MERS-CoV spike protein; (3) a novel recombinant chimeric influenza A H1N1 pandemic (A/California/04/2009) (5+3) as a vector to express an immunogenic short peptide residue of MERSCoV spike protein to elucidate immunity against MERS-CoV and H1N1pdm09. This study included the molecular characterization and serological analysis of 5693 samples. Interestingly, collected samples from camels have showed relatively high seropositivity for sera samples (71.2%). Nevertheless, for other types of collected samples which were tested by RT-PCR, the positivity rate was low and variable: nasal (15.4%), rectal (15.8%), milk (6.4%) and urine (0%). The imported camels showed higher percent in sera and viral prevalence than local one. The full genome sequences of Egyptian MERS-CoVs are grouped with a novel clade C out of clades A and B. Interestingly, the results of developed vaccine trials showed that BALB/c mice vaccinated with pcDNA3.1-S and pcDNA3.1-N gave potent neutralizing antibodies (nAbs) against MERS-CoV. The novel recombinant OMV-H1-RBD and the two chimeric rescued inactivated rgH1N1-peptide-MERS-CoVs stimulated a protective nAbs against H1N1pdm09 and MERS-CoV in vaccinated mice. This study is providing evidences that camels are the main reservoirs for MERS-CoV and surveillance in African exporting countries is urgently required. Also to control MERS-CoV, DNA vaccines of S and N encoded protein are highly recommended. The novel recombinant OMVs vaccine and two chimeric influenza virus with immunogenic peptide of MERS-CoV is can serve as effective bivalent vaccine to combat both H1N1pdm09 and MERS-CoV infections
2018
Ph.d
Ain Shams
Science