Journal Article

Antibody-mediated protection against MERS-CoV in the murine model

Butcher, W., Moore, B.D., Gibson, L.C.D., Williamson, E.D., Mahood, R., Harvey, R., Macleod, C., Almond, N., Bogus, M., Lever, M.S., O'Brien, L., Weller, S.A., New, R.R.C., Bayliss, M., Smither, S.

2019

Overview

•A novel dual route vaccination using the MERS-CoV RBD sub-unit has been developed.•Murine antisera induced to the RBD protein , were neutralising in vitro.•MERS-CoV susceptibility was induced in naïve mice with Ad5hDPP4.•Passive transfer of anti-RBD sera protected susceptible mice.•Protected mice had a significantly reduced viral titre (P = 0.02) in their lungs. Murine antisera with neutralising activity for the coronavirus causative of Middle East respiratory syndrome (MERS) were induced by immunisation of Balb/c mice with the receptor binding domain (RBD) of the viral Spike protein. The murine antisera induced were fully-neutralising in vitro for two separate clinical strains of the MERS coronavirus (MERS-CoV). To test the neutralising capacity of these antisera in vivo, susceptibility to MERS-CoV was induced in naive recipient Balb/c mice by the administration of an adenovirus vector expressing the human DPP4 receptor (Ad5-hDPP4) for MERS-CoV, prior to the passive transfer of the RBD-specific murine antisera to the transduced mice. Subsequent challenge of the recipient transduced mice by the intra-nasal route with a clinical isolate of the MERS-CoV resulted in a significantly reduced viral load in their lungs, compared with transduced mice receiving a negative control antibody. The murine antisera used were derived from mice which had been primed sub-cutaneously with a recombinant fusion of RBD with a human IgG Fc tag (RBD-Fc), adsorbed to calcium phosphate microcrystals and then boosted by the oral route with the same fusion protein in reverse micelles. The data gained indicate that this dual-route vaccination with novel formulations of the RBD-Fc, induced systemic and mucosal anti-viral immunity with demonstrated in vitro and in vivo neutralisation capacity for clinical strains of MERS-CoV.

• Publisher: Elsevier Ltd,Elsevier Limited,Published by Elsevier Ltd
• Subject: Adenoviridae / Adenoviruses / Allergy and Immunology / Animal models / Antibodies / Antigens / Antisera / antiserum / Antiviral agents / Calcium phosphates / Coronaviridae / Coronavirus / Coronaviruses / Fatalities / Formulations / Fusion protein / humans / humoral immunity / Immunity / Immunization / Immunoglobulin G / In vivo methods and tests / Infections / Lungs / MERS / mice / micelles / Microcrystals / Middle East respiratory syndrome coronavirus / Mucosa / Mucosal immunity / Neutralising antibody / Novel vaccine formulation / Oral administration / Proteins / Respiratory infection / Reverse micelles / Spike protein / Systemic immunity / Vaccination / Vaccines / viral load