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1.  Complex of a protective antibody with its Ebola virus GP peptide epitope: unusual features of a Vλx-light chain 
Journal of molecular biology  2007;375(1):202-216.
13F6-1-2 is a murine monoclonal antibody that recognizes the heavily glycosylated mucin-like domain of the Ebola virus virion-attached glycoprotein (GP) and protects animals against lethal viral challenge. Here we present the crystal structure, at 2.0 Å, of 13F6-1-2 in complex with its Ebola virus GP peptide epitope. The GP peptide binds in an extended conformation, anchored primarily by interactions to the heavy chain. Two GP residues, Gln P406 and Arg P409, make extensive side chain hydrogen bond and electrostatic interactions to the antibody and are likely critical for recognition and affinity. The 13F6-1-2 antibody utilizes a rare Vλx light chain. The three light chain complementarity determining regions (CDRs) do not adopt canonical conformations and represent new classes of structures distinct from Vκ and other Vλ light chains. In addition, although Vλx had been thought to confer specificity, all light chain contacts are mediated through germline-encoded residues. This structure of an antibody that protects against the Ebola virus now provides a framework for humanization and development of a post-exposure immunotherapeutic.
doi:10.1016/j.jmb.2007.10.017
PMCID: PMC2173910  PMID: 18005986
Ebola virus; Vλx light chain; glycoprotein; neutralizing antibody; new canonical structures of immunoglobulins; hypervariable loops; complementarity determining region; Fab-peptide complex
2.  Protective Cytotoxic T-Cell Responses Induced by Venezuelan Equine Encephalitis Virus Replicons Expressing Ebola Virus Proteins 
Journal of Virology  2005;79(22):14189-14196.
Infection with Ebola virus causes a severe disease accompanied by high mortality rates, and there are no licensed vaccines or therapies available for human use. Filovirus vaccine research efforts still need to determine the roles of humoral and cell-mediated immune responses in protection from Ebola virus infection. Previous studies indicated that exposure to Ebola virus proteins expressed from packaged Venezuelan equine encephalitis virus replicons elicited protective immunity in mice and that antibody-mediated protection could only be demonstrated after vaccination against the glycoprotein. In this study, the murine CD8+ T-cell responses to six Ebola virus proteins were examined. CD8+ T cells specific for Ebola virus glycoprotein, nucleoprotein, and viral proteins (VP24, VP30, VP35, and VP40) were identified by intracellular cytokine assays using splenocytes from vaccinated mice. The cells were expanded by restimulation with peptides and demonstrated cytolytic activity. Adoptive transfer of the CD8+ cytotoxic T cells protected filovirus naïve mice from challenge with Ebola virus. These data support a role for CD8+ cytotoxic T cells as part of a protective mechanism induced by vaccination against six Ebola virus proteins and provide additional evidence that cytotoxic T-cell responses can contribute to protection from filovirus infections.
doi:10.1128/JVI.79.22.14189-14196.2005
PMCID: PMC1280180  PMID: 16254354

Results 1-2 (2)