Abstract
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.
| Language | English |
|---|---|
| Pages | 4094-4102 |
| Number of pages | 9 |
| Journal | Vaccine |
| Volume | 37 |
| Issue number | 30 |
| Early online date | 6 Jun 2019 |
| DOIs | |
| Publication status | Published - 9 Jul 2019 |
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Keywords
- coronavirus
- MERS
- mucosal immunity
- neutralising antibody
- novel vaccine formulation
- respiratory infection
- systemic immunity
- vaccination
Cite this
}
Antibody-mediated protection against MERS-CoV in the murine model. / New, R.R.C.; Moore, B.D.; Butcher, W.; Mahood, R.; Lever, M.S.; Smither, S.; O'Brien, L.; Weller, S.A.; Bayliss, M.; Gibson, L.C.D.; Macleod, C.; Bogus, M.; Harvey, R.; Almond, N.; Williamson, E.D.
In: Vaccine, Vol. 37, No. 30, 09.07.2019, p. 4094-4102.Research output: Contribution to journal › Article
TY - JOUR
T1 - Antibody-mediated protection against MERS-CoV in the murine model
AU - New, R.R.C.
AU - Moore, B.D.
AU - Butcher, W.
AU - Mahood, R.
AU - Lever, M.S.
AU - Smither, S.
AU - O'Brien, L.
AU - Weller, S.A.
AU - Bayliss, M.
AU - Gibson, L.C.D.
AU - Macleod, C.
AU - Bogus, M.
AU - Harvey, R.
AU - Almond, N.
AU - Williamson, E.D.
PY - 2019/7/9
Y1 - 2019/7/9
N2 - 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.
AB - 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.
KW - coronavirus
KW - MERS
KW - mucosal immunity
KW - neutralising antibody
KW - novel vaccine formulation
KW - respiratory infection
KW - systemic immunity
KW - vaccination
UR - http://www.scopus.com/inward/record.url?scp=85066780154&partnerID=8YFLogxK
U2 - 10.1016/j.vaccine.2019.05.074
DO - 10.1016/j.vaccine.2019.05.074
M3 - Article
VL - 37
SP - 4094
EP - 4102
JO - Vaccine
T2 - Vaccine
JF - Vaccine
SN - 0264-410X
IS - 30
ER -