RSV19

Antibody Name: RSV19 (IgG2a | k) (VH SGIIC | VL SGII)
References: Tempest, P.R., Bremner, P., Lambert, M., Taylor, G., Furze, J.M., Carr, F.J. and Harris, W.J. "Reshaping a human monoclonal antibody to inhibit human respiratory syncytial virus infection in vivo" Bio/Tech. (1991) 9: 266-271.
Everitt, D.E., Davis, C.B., Thompson, K. et al. "The pharmacokinetics, antigenicity and fusion-inhibition activity of RSHZ19, a humanized monoclonal antibody to respiratory syncytial virus, in healthy volunteers" J. Infect. Dis. (1996) 174:463-469.
Donor Antibody: mouse
Acceptor Antibody: Human IgG1 | k
Antigen: Fusion (F) protein of Respiratory Syncytial Virus (RSV)
Laboratory: Scotgen, Aberdeen; Univ. of Aberdeen; AFRC Inst. Animal Health, UK
Design: "Ordered steps of additional alterations to achieve the minimal number of changes to the human structure necessary to restore binding affinity and specificity".
Frameworks: VH human NEWM | VL human REI (modified as in Campath-1H.)
CDRs: All 6 from VH and VL, Kabat Definition.
Backmutations: YCAR91-94FCNS:H (The R94 may interact with D101 in CDR-H3 and was removed).
S27F:H change not mentioned in the text.
Binding: Best binder version rsv19vhfns. Significant reduction in binding (>10-fold) measured by ELISA, but no direct comparison with the mouse mAb since no chimaeric mAb was available to use as a positive control.
Expression: Rat YB2/0 myeloma cells from ATCC
Comment: The humanised mAb showed both in vitro and in vivo biological activity.
Clinical Indication: Acute respiratory illness in young children. The humanised mAb was effective against a wide range of clinical isolates of RSV.

explanation of symbols and abbreviations

José Saldanha © 1997-8. Birkbeck College, London WC1E 7HX.