HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Mekseepralard, C. Articles by Routledge, E. G. Search for Related Content PubMed PubMed Citation Articles by Mekseepralard, C. Articles by Routledge, E. G. Agricola Articles by Mekseepralard, C. Articles by Routledge, E. G.

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

C. Mekseepralard

E. G. Routledge

The Schools of Clinical Medical Sciences and Cell and Molecular Biosciences, The University of Newcastle upon Tyne, Newcastle upon Tyne NE2 4HH, UK

Correspondence
G. L. Toms
Geoffrey.Toms{at}ncl.ac.uk

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, 1C2, the V_H and V_L genes were isolated by RT-PCR and assembled with human light-chain and human 1 heavy-chain constant-region genes to form two mouse–human chimaeras, which were expressed in NS0 cells. One of the chimaeras carried a wild-type 1 chain, whilst the other had an aglycosyl mutation in the C_H2 domain rendering the antibody defective in complement activation and FcR 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 1 chimaeric antibody, no virus could be recovered from the lungs 4 days after intranasal inoculation of HRSV. In mice immunized with the aglycosyl 1 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 pathways.

Present address: Department of Microbiology, Faculty of Medicine, Srinakharinwirot University, Sukhumvit 23, Bangkok 10100, Thailand.

Present address: Angel Biotechnology, 44 Colbourne Crescent, Nelson Park Industrial Estate, Cramlington, Northumberland NE23 1WB, UK.