Preservation of surface-dependent properties of viral antigens following immobilization on particulate ceramic delivery vehicles.
B-cell stimulation for the purpose of evoking an effective neutralizing humoral immune response is a surface phenomenon that is exquisitely specific to antigen conformation. Consequently, successful delivery of antigen, such as would be desired in a vaccine, entails preservation of an antigen's apparent native surface (conformational) properties. Prior to testing the actual vaccinating efficacy of delivered antigens, the surface properties could be assessed through a variety of in vitro and in vivo assays in which the measurement standard would be the properties of the antigens in their native state (whole virus). Using surface modified nanocrystalline carbon and calcium-phosphate ceramic particulates (carbon ceramics and brushite), we evaluated the surface activity of immobilized non-nuclear material extracted from HIV-1. Physical characterization showed that the particles with immobilized antigen ("HIV decoys") measured 50 nm in diameter (HIV = 50-100 nm) and exhibited the same zeta potentials as whole (live) HIV. In vitro testing showed that the HIV decoys were recognized by both conformationally nonspecific and specific monoclonal antibodies, were recognized by human IgG from HIV antibody-positive patients, and could promote surface agglomeration among malignant T-cells similar to live HIV. Last, in vivo testing in three vaccinated animal species showed that the HIV decoys elicited humoral and cellular immune responses similar to that evoked by whole (live) HIV.
Kossovsky
N
N
Department of Pathology, University of California, Los Angeles School of Medicine 90024-1732, USA.
Gelman
A
A
Sponsler
E
E
Rajguru
S
S
Torres
M
M
Mena
E
E
Ly
K
K
Festekjian
A
A
D000818:Animals; D000911:Antibodies, Monoclonal / Q000032:analysis; D015153:Blotting, Western; D002482:Cellulose; D002516:Ceramics; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D006168:Guinea Pigs; D015488:HIV Antigens / Q000008:administration & dosage / Q000032:analysis / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology* / Q000648:ultrastructure; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008854:Microscopy, Electron; D010316:Particle Size; D011208:Powders; D011817:Rabbits; D012882:Skin Tests; D013499:Surface Properties; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism
D000911:Antibodies, Monoclonal; D015488:HIV Antigens; D011208:Powders; D002482:Cellulose