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Safety and pharmacokinetics of a chimerized anti-lipoteichoic acid monoclonal antibody in healthy adults
- Source :
- International Immunopharmacology. 9:639-644
- Publication Year :
- 2009
- Publisher :
- Elsevier BV, 2009.
-
Abstract
- A chimerized (murine/human) monoclonal antibody (pagibaximab) against lipoteichoic acid (LTA) and protective in animal models for coagulase-negative staphylococci (CONS) and Staphylococcus aureus bacteremia, was developed for prevention of staphylococcal infection in high-risk populations. This open label two-dose study of a single intravenous dose of 3 or 10 mg/kg of pagibaximab evaluated the safety/tolerability, pharmacokinetics, and opsonophagocytic activity of pagibaximab in healthy adults. Eight participants were enrolled (four in each dose group). No infusion, drug, or dose related adverse events occurred. Serum anti-LTA levels were dose-related; mean concentrations peaked at 87.75 and 259.24 microg/mL for 3 and 10 mg/kg groups, respectively. The half-life (beta) of pagibaximab was approximately 33 days. Opsonophagocytic activity of serum samples on a human clinical isolate of Staphylococcus epidermidis in a standard bacterial killing assay was dose-related, and peaked at a mean of 88.5 and 95.5% at 1:90 dilution for 3 and 10 mg/kg groups, respectively. Serum anti-LTA and opsonophagocytic activity levels exhibited statistically significant correlation. The results suggest that pagibaximab at 3 and 10 mg/kg administered as a single intravenous dose in healthy adults appears to: 1) provide preliminary safety and tolerability data, 2) produce dose-related serum anti-LTA and opsonophagocytic activity levels, 3) have a half-life similar to other immunoglobulin G1 antibodies, 4) exhibit statistically significant correlation between serum anti-LTA and opsonophagocytic activity levels. This study supports conducting safety and pharmacokinetic trials of pagibaximab in populations at high-risk of developing CONS infection.
- Subjects :
- Adult
Lipopolysaccharides
Male
Staphylococcus aureus
Neutrophils
Recombinant Fusion Proteins
Immunology
Staphylococcal infections
Mice
Serum Bactericidal Test
Phagocytosis
Pharmacokinetics
Staphylococcus epidermidis
medicine
Animals
Humans
Immunology and Allergy
Pagibaximab
Pharmacology
Dose-Response Relationship, Drug
biology
Antibodies, Monoclonal
Middle Aged
Staphylococcal Infections
medicine.disease
biology.organism_classification
Anti-Bacterial Agents
Teichoic Acids
Tolerability
Injections, Intravenous
Toxicity
biology.protein
Female
Antibody
Half-Life
medicine.drug
Subjects
Details
- ISSN :
- 15675769
- Volume :
- 9
- Database :
- OpenAIRE
- Journal :
- International Immunopharmacology
- Accession number :
- edsair.doi.dedup.....8fb28876affa6a6c5f4151ed20d11f71
- Full Text :
- https://doi.org/10.1016/j.intimp.2009.02.008