Publication:
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

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Issued Date

2006

Resource Type

Article

File Type

application/pdf

ISSN

221317

DOI

10.1099/vir.0.81660-0

Other identifier(s)

2-s2.0-33646146936

Rights Holder(s)

Scopus

Bibliographic Citation

Journal of General Virology. Vol 87, No.5 (2006), p.1267-1273

Suggested Citation

Mekseepralard C., Toms G.L., Routledge E.G. 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. Journal of General Virology. Vol 87, No.5 (2006), p.1267-1273. doi:10.1099/vir.0.81660-0 Retrieved from: https://hdl.handle.net/20.500.14740/5796

Title

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

Author(s)

Mekseepralard C.
 Toms G.L.
 Routledge E.G.

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.

Subject(s)

Alemtuzumab
 Epitope
 Fc receptor
 Immunoglobulin Fc fragment
 Immunoglobulin G
 Immunoglobulin heavy chain
 Immunoglobulin light chain
 Immunoglobulin subclass
 Respiratory syncytial virus vaccine
 Thrombospondin
 Animal cell
 Animal experiment
 Animal model
 Animal tissue
 Antigen binding
 Article
 Chimera
 Complement activation
 Controlled study
 Enzyme linked immunosorbent assay
 Female
 Gene isolation
 Gene mutation
 Genetic conservation
 Human
 Human cell
 Immunoglobulin gene
 Immunoglobulin variable region
 Infection prevention
 Inoculation
 Mouse
 Nonhuman
 Passive immunization
 Priority journal
 Protein assembly
 Protein domain
 Protein expression
 Protein function
 Protein glycosylation
 Respiratory syncytial pneumovirus
 Reverse transcription polymerase chain reaction
 Virus infection
 Virus neutralization
 Virus titration
 Wild type
 Animals
 Antibodies, Monoclonal
 Antibodies, Viral
 Epitopes
 Humans
 Immunization, Passive
 Immunoglobulin G
 Injections, Intravenous
 Mice
 Mice, Inbred BALB C
 Neutralization Tests
 Respiratory Syncytial Virus Infections
 Respiratory Syncytial Virus, Human
 Viral Fusion Proteins
 Chimaeriformes
 Human respiratory syncytial virus
 Hydrangea ringspot virus
 Murinae
 Rodentia
 Subgroup A

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URI

https://hdl.handle.net/20.500.14740/5796

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Scopus: Year 1983-2021

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