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Protection of mice against Human respiratory syncytial virus by wild-type and aglycosyl mouse-human chimaeric lgG antibodies to subgroup-conserved epitopes on the G glycoprotein

Lookup NU author(s): Dr Chantana Mekseepralard, Professor Geoff Toms, Dr Edward Routledge

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Abstract

Monoclonal antibodies (mAbs) to conserved epitopes on the G glycoprotein of human respiratory syncytial virus (HRSV) subgroup A fail to neutralize the virus in cell culture in the absence of complement, but are protective in rodent models of infection. They may have potential as prophylactic agents in human infants. In order to investigate the role of Fc-dependent pathways in protection by one such antibody, 1 C2, the VH and VL genes were isolated by RT-PCR and assembled with human κ light-chain and human γ1 heavy-chain constant-region genes to form two mouse-human chimaeras, which were expressed in NSO cells. One of the chimaeras carried a wild-type γ1 chain, whilst the other had an aglycosyl mutation in the CH2 domain rendering the antibody defective in complement activation and FcγR binding. Whilst both chimaeric antibodies exhibited similar avidity for HRSV in ELISA, only the fully glycosylated wild type was capable of neutralizing the virus in the presence of complement. In mice passively immunized with either murine or wild-type γ1 chimaeric antibody, no virus could be recovered from the lungs 4 days after intranasal inoculation of HRSV. In mice immunized with the aglycosyl γ1 chimaera, however, virus was present in the lungs following challenge, although virus titres were significantly reduced compared with controls (P<0.005). These results indicate that the protective effect of this antibody is mediated by both Fc-dependent and Fc-independent pathway. © 2006 SGM.


Publication metadata

Author(s): Mekseepralard C, Toms GL, Routledge EG

Publication type: Article

Publication status: Published

Journal: Journal of General Virology

Year: 2006

Volume: 87

Issue: 5

Pages: 1267-1273

ISSN (print): 0022-1317

ISSN (electronic): 1465-2099

Publisher: Society for General Microbiology

URL: http://dx.doi.org/10.1099/vir.0.81660-0

DOI: 10.1099/vir.0.81660-0

PubMed id: 16603529


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