In vitro and in vivo activity of polyclonal and monoclonal human immunoglobulins G, M, and A against Pseudomonas aeruginosa lipopolysaccharide

Abstract

We evaluated the in vitro opsonophagocytic killing activity of monoclonal human immunoglobulin G (IgG), IgM, and IgA specific for Pseudomonas aeruginosa lipopolysaccharide and the in vivo protective capacity in neutropenic mice of both monoclonal and purified polyclonal IgG, IgM, and IgA. Monoclonal IgM was efficacious in mediating opsonophagocytic killing only in conjunction with complement, whereas monoclonal IgG opsonic killing was potentiated by complement, and monoclonal IgA opsonic killing was independent of complement. These findings are similar to those previously reported for purified polyclonal IgM, IgG, and IgA. The monoclonal and polyclonal immunoglobulins had comparable 50% protective doses in neutropenic mice (range, 0.28 to 0.46 microgram per mouse). The protective activity of IgM in neutropenic mice was abolished by cobra venom factor treatment, whereas IgG and IgA maintained efficacy in cobra venom factor-treated mice. These data indicate that all three major human serum immunoglobulin isotypes have opsonophagocytic and protective activities against P. aeruginosa, with a critical role for complement in the function of IgM.

Feasibility of prophylaxis and therapy against Gram-negative infections by human monoclonal antibodies

“…We show that a single injection of 5 ~g HmAbs is effective in protecting mice from P. aeruginosa sepsis and that the time of antibody administration is of crucial importance in producing this protective effect. Consistent with previous results the prophylactic administration of antibody was effective in protecting mice from shock and death [7][8][9][10]14,16]. In addition, we demonstrate that serotype-specific HmAbs are of equal efficacy when administered 6 h after challenge, but that protection is diminished if injected 18 h after challenge.…”

“…As a consequence, human hyperimmune globulin preparations enriched with antibodies against the most prevalent Gram-negative nosocomial pathogens have been produced from the plasma of donors immunized with vaccines containing serotype-specific antigens and are currently under clinical evaluation [6]. To date the evaluation of serotype-specific HmAbs for efficacy in animal models has been generally limited to prophylactic use [7][8][9][10].…”

Pseudomonas aeruginosa-specific IgG1 and IgG2 subclasses in enhancement of pulmonary clearance following passive immunisation in the rat

“…of pooled data from three experiments. The number of rats per group is: Unt (15), I-1 mg (5), I-5 (10), NI-1 (5) and NI-5(9). *Signi¢cantly di¡erent from the Unt group; # signi¢cantly di¡erent from both the Unt and NI-5 groups.…”

Pharmacodynamic and Protective Properties of a Murine Lipopolysaccharide‐Specific Monoclonal Antibody in Experimental Pseudomonas aeruginosa Pneumonia in Mice

“…ET Al, particularly lipopolysaccharide (LPS) or endotoxin, may provide the basis for effective adjuvant therapy in this disease (10). Monoclonal antibodies (MAbs) reactive with surface-exposed antigens of P. aeruginosa have been evaluated in different animal models of Pseudomonas disease (13,17,19,20,(24)(25)(26). MAbs specific for the O-side chain component of P. aeruginosa LPS have been tested with varying success in guinea pig and mouse models of Pseudomonas pneumonia (3,11,27).…”