Antiviral immunotoxins: antibody-mediated delivery of gelonin inhibits Pichinde virus replication in vitro.
Immunotoxins were produced and evaluated for antiviral activity against Pichinde virus, a member of the family Arenaviridae. Immunoglobulins were conjugated to the ribosome-inactivating protein, gelonin, through a disulfide linkage to form the immunotoxins. Immunotoxins were produced utilizing monoclonal antibodies, immunoglobulin-binding proteins and hyperimmune sera. An immunotoxin consisting of hyperimmune rabbit sera conjugated with gelonin displayed strong antiviral activity against Pichinde virus, as did a protein G-gelonin indirect immunotoxin in combination with nonconjugated hyperimmune sera. Hyperimmune rabbit sera conjugated with gelonin caused no detectable cytotoxicity in non-infected Vero cells as measured by [3H]leucine incorporation. The 50% effective dose for the immunotoxin was 0.018 microM compared with 86 microM for ribavirin.
Barnett
B B
BB
Department of Biology, Utah State University, Logan 84322-5500.
Burns
N J
NJ
Park
K J
KJ
Dawson
M I
MI
Kende
M
M
Sidwell
R W
RW
D000818:Animals; D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D006477:Arenaviruses, New World / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D002474:Cell-Free System; D000922:Immunotoxins / Q000494:pharmacology*; D007930:Leucine / Q000378:metabolism; D010940:Plant Proteins / Q000494:pharmacology*; D014176:Protein Biosynthesis; D012254:Ribavirin / Q000494:pharmacology; D054789:Ribosome Inactivating Proteins, Type 1; D014709:Vero Cells; D014779:Virus Replication / Q000187:drug effects
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D000922:Immunotoxins; D010940:Plant Proteins; D054789:Ribosome Inactivating Proteins, Type 1; D012254:Ribavirin; C025674:GEL protein, Gelonium multiflorum; D007930:Leucine