Further Characterization of the Fate of Human Monoclonal Antibodies in Rhesus Monkeys

Abstract

We have shown previously that human monoclonal antibodies are not very immunogenic in rhesus monkeys, with only one monkey out of five mounting an anti-monoclonal antibody response. Two additional monkeys have been injected multiple times with much larger amounts of one human monoclonal antibody. No anti-antibody response has been detected in these monkeys. Structural changes that occur in the monoclonal antibodies over time in vivo have been investigated by Western Blots using anti-idiotypic antisera. Sodium dodecyl sulfate gel electrophoresis reveals that very little antibody has altered molecular weight. Isoelectric focusing patterns change more dramatically. Forms of the antibodies with lower isoelectric points appear in the serum. These forms have a similar in vivo half-life as the freshly prepared antibody. Very low pI forms of the monoclonal antibodies are not detected in the serum. Isoelectric focusing can be used to determine the in vivo or in vitro condition of a monoclonal antibody preparation. Finally, the monkey anti-human IgG that arose in the single monkey studied previously has been further characterized.

Identification of the gene coding for rhesus cytomegalovirus glycoprotein B and immunological analysis of the protein.

“…The HCMV-specific human and murine monoclonal antibodies have been described before : 89-104 (Wagner et al, 1992), MSL-109 (Ehrlich et al, 1988), the ITC series (Ohlin et al, 1993), 27-156, 27-287 (Schoppel et al, 1996. The antisera aSgB-1 and aSgBNH were raised by standard methods in rabbits by immunizing the animals with purified recombinant proteins (Harlow et al, 1988).…”

Glycoprotein H of human cytomegalovirus is a major antigen for the neutralizing humoral immune response

“…To further analyse the antigenically relevant structures of gH expressed in insect cells, indirect immunofluorescence analyses were performed with a panel of MAbs which included the murine antibodies 14-4b, 109, 5, 442, 115 and AP86-SA4, and the human MAb SDZ 89-109 (Ehrlich et al, 1988;Simpson et al, 1993;Urban et al, 1992). Since all these antibodies are capable of neutralizing HCMV it is assumed that they bind to native gH on the envelope of HCMV virions.…”

Identification of Chimpanzee Fab Fragments by Repertoire Cloning and Production of a Full-Length Humanized Immunoglobulin G1 Antibody That Is Highly Efficient for Neutralization of Dengue Type 4 Virus

“…Furthermore, in the C H 1 or C L region, there was only one amino acid (or approximately 1.0%) difference between chimpanzee and human sequences (data not shown) (16,59). The high level of antibody sequence similarity and a number of other observations addressing this issue suggest the possibility that chimpanzee antibodies may be administered directly to humans without further modifications to humanize these reagents (16,17). Experimental data available indicate that little immunogenicity is seen when components of human antibodies are introduced into chimpanzees (46).…”