Pharmacokinetic and pharmacodynamic study of a clinically effective anti-CD2 monoclonal antibody
SCANDINAVIAN JOURNAL OF IMMUNOLOGY
Authors: Sellberg, Felix; Berglund, David; Binder, Christian; Hope, James; Fontenot, Jane; Griesemer, Adam; Sykes, Megan; Sachs, David H.; Berglund, Erik
Abstract
The humanized IgG1 kappa monoclonal antibody siplizumab and its rat parent monoclonal IgG2b antibody BTI-322 are directed against the CD2 antigen. Siplizumab is species-specific, reacting with human and chimpanzee cells but not with cells from any other species, including other non-human primates. Because siplizumab treatment has recently shown great potential in clinical transplantation, we now present the results of our previous pharmacokinetic, pharmacodynamic and safety studies of both antibodies. Fourteen chimpanzees received 1-3 doses of 0.143 to 5.0 mg/kg iv The effects were followed with flow cytometry on peripheral lymphocytes and staining of lymph nodes. Side effects were recorded. Serum antibody concentrations were followed. Across the doses, a rapid, transient depletion of CD2, CD3, CD4 and CD8 lymphocytes and NK cells was observed for both antibodies. Immune reconstitution was more rapid for BTI-322 compared to siplizumab. Paracortical lymph node T cell depletion was moderate, estimated at 45% with doses of >0.6 mg/kg. Restoration of lymph node architecture was seen after two weeks to two months for all animals. All four subjects receiving BTI-322 experienced AEs on the first dosing day, while the eight subjects dosed with siplizumab experienced few mild, transient AEs. Infusion with siplizumab and BTI-322 resulted in rapid depletion of CD2(+) cells in circulation and tissue. Siplizumab had a longer t(1/2) and fewer AEs compared to BTI-322.
Immunization with 3-oxododecanoyl-L-homoserine lactone-r-PcrV conjugate enhances survival of mice against lethal burn infections caused by Pseudomonas aeruginosa
BOSNIAN JOURNAL OF BASIC MEDICAL SCIENCES
Authors: Golpasha, Isar Dejban; Mousavi, Seyed Fazlollah; Owlia, Parviz; Siadat, Seyed Davar; Irani, Shiva
Abstract
Quorum Sensing and type III secretion system play an important role in the virulence of Pseudomonas (P.) aeruginosa in burn wound infections. We aimed to explore the feasibility of using 3-oxo-C-12-HSL-r-PcrV conjugate as a candidate vaccine against P aeruginosa caused infections. 3-oxo-C-12-HSL-r-PcrV conjugate was prepared and used for immunization of mice (lo pig, subcutaneous, three times, at 2-week intervals). Mice were divided into five groups: I: PcrV; II: 3-oxo-C-12-HSL-r-PcrV 1.tg); III: 3-oxo-C-12-HSL-r-PcrV (20 1.1g); IV: 3-oxo-C-12-HSL; and V: PBS receiving groups. After each shot of immunization, total and isotype antibody responses against corresponding antigen were measured to determine the immunization efficacy. One month after the last immunization, all groups were burned and challenged subeschar with P aeruginosa PAO1. Survival rate and bacterial quantity in the skin and internal organs (liver and spleen) were evaluated 25-hr after burn infection. Immunization with 3-oxo-C-12-HSL-r-PcrV significantly increased total IgG and specific subclass antibodies (IgGi, IgG2a, IgG2b, and IgM) in the serum of the groups II and III compared to the control group (p