M. of 1 1,877, 7,571, 24,923, and 83,197 ng/ml following doses of 0.1, 0.4, 1.2, and 4.0 mg/kg body weight, respectively. The mean elimination half-life was between 70 and 95 h. The mean volume of distribution was between 4.76 and 5.47 liters. Clearance ranged between 0.039 and 0.120 liters/h. At the highest dose of 4.0 mg/kg, plasma KBPA-101 levels were greater than 5,000 mogroside IIIe ng/ml for 14 days. mogroside IIIe KBPA-101 exhibited linear kinetics across all doses. No anti-KBPA-101 antibodies were detected after dosing in any subject. Overall, the human monoclonal antibody KBPA-101 was well tolerated over the entire dose range in healthy volunteers, and no serious adverse events have been reported. Hospital-acquired (nosocomial) infections are responsible for an increasing number of serious secondary illnesses in the hospital environment. Immunocompromised individuals including burn victims, incubated patients in the intensive care unit, cancer and AIDS patients, as well as patients undergoing organ transplantation are at particularly high risk of contracting nosocomial infections. and spp., is one of the most common pathogens responsible for nosocomial infections (6, 13). expresses a variety of membrane-bound virulence factors such as lipopolysaccharide (LPS), pili, flagella, as well as secreted compounds, such as exoenzyme S and exotoxin A, that interfere with host defense systems (2, 14). LPS in particular is responsible for the development of septic shock, a condition associated with extremely poor outcomes. Considerable amounts of LPS can be released from the bacterial membrane during antibiotic treatment and can aggravate the systemic inflammatory response. The treatment of infections is a challenge due mainly to its poor outer membrane permeability and/or efflux that results in intrinsic resistance to many antimicrobial agents. In addition, often harbors chromosomal and/or plasmid-mediated genes that encode antimicrobial resistance mechanisms, enabling it to acquire resistance to almost every class of antimicrobial agent available (3, 7). The major defense mechanisms counteracting gram-negative bacterial infections are complement-activated killing and complement-mediated opsonophagocytosis. Polysaccharides such as LPS are T-cell-independent antigens that trigger the innate immune system via the stimulation of pattern recognition receptors (e.g., Toll-like receptor 4). Antibodies induced in response to them are mostly of the immunoglobulin M SAV1 (IgM) isotype. IgM antibodies have several favorable properties that support their use as therapeutic tools: their pentameric form provides 10 antigen binding sites, they bind antigens with high avidity, and IgM antibodies are very mogroside IIIe effective complement activators (18). Passive immunotherapy has long been recognized as a valuable addition to standard therapy against infectious diseases. The use of monoclonal antibodies (MAbs) has been established in several therapeutic areas and might represent an alternative or complement to antibiotic therapy. Combined treatment with MAbs and antibiotics may lead to a more rapid resolution of infections, resulting in shorter stays in intensive care units as well as reductions of morbidity, mortality, and health care costs. Currently, MAbs are derived from mice and genetically modified to improve tolerability in humans. Nevertheless, these so-called humanized antibodies possess remainders of potentially antigenic sequences and mogroside IIIe differ in glycosylation patterns from human antibodies. These differences can affect half-life and long-term tolerability. Therefore, a technique to utilize human B cells for the production of therapeutic MAbs has been developed. KBPA-101 is a human MAb obtained from a volunteer immunized with a O-polysaccharide toxin A conjugate vaccine (10, 11). It is of IgM/ isotype and directed against the LPS O-polysaccharide moiety of serotype IATS O11. Preclinical tests with KBPA-101 included systemic infections in a murine burn wound sepsis model, where full protection of animals against lethal challenges with was achieved at very low doses of 5 g/animal. Also, an acute lung infection model using mice showed protection against local respiratory infections. Although KBPA-101 is derived from a human donor, there are potential safety concerns associated with the use of MAbs, including immunological and hypersensitivity reactions. Since KBPA-101 is mogroside IIIe selected for its species-specific effector function and the targeted antigen is not expressed endogenously in humans, no crossover reactivity with autoantigens is expected. The aim of this single-center, double-blind, dose escalation phase I study was to evaluate the safety and pharmacokinetic profile of.