MeawandMoo1 schreef:
Zo..
Crucell heeft weer een antal monoclonal antibodies ontdekt met neutraliserende werking na oplopen van een infectie.
Vergelijking met Rabies:
Ook hier overleven de meeste muisjes na ontvangst van een dodelijke infectie.
[quote=Crucell]
Herein, we characterize in detail two WNV-specific human MAbs, CR4348 and CR4354, that were isolated from B cell populations of convalescent patients. These MAbs strongly neutralize WNV infection of cultured cells, protect mice against lethal infection in vivo,
[/quote]
Human Monoclonal Antibodies Induced by Natural Infection Against West Nile Virus Neutralize at a Post-Attachment Step.
Vogt MR, Moesker B, Goudsmit J, Jongeneelen M, Austin SK, Oliphant T, Nelson S, Pierson TC, Wilschut J, Throsby M, Diamond MS.
Departments of Pathology and Immunology, Molecular Microbiology, Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Medical Microbiology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands; Crucell Holland B.V., 2301 CA, Leiden, The Netherlands; Viral Pathogenesis Section, Laboratory of Viral Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
West Nile virus (WNV) is a neurotropic flavivirus that is now a primary cause of epidemic encephalitis in North America. Studies in mice have demonstrated that the humoral immune response against WNV limits primary infection and protects against a secondary challenge. The most potent neutralizing mouse monoclonal antibodies (MAbs) recognize an epitope on the lateral ridge of domain III (DIII-lr) of the envelope (E) protein. However, studies with serum from human patients show that antibodies against the DIII-lr epitope comprise at best, a minor component of the human anti-WNV antibody response. Herein, we characterize in detail two WNV-specific human MAbs, CR4348 and CR4354, that were isolated from B cell populations of convalescent patients. These MAbs strongly neutralize WNV infection of cultured cells, protect mice against lethal infection in vivo, and yet poorly recognize recombinant forms of E protein. Instead, CR4348 and CR4354 bind determinants on intact WNV virions and subviral particles in a pH-sensitive manner, and neutralization is altered by mutations at the dimer interface in domain II and the hinge between domains I and II, respectively. CR4348 and CR4354 human MAbs neutralize infection at a post-attachment step in the viral lifecycle, likely by inhibiting acid-induced fusion within the endosome.
www.ncbi.nlm.nih.gov/pubmed/19386704