Porcine humoral immune responses to multiple injections of murine monoclonal antibodies.
In humans and cattle, multiple injections of murine monoclonal antibodies (m-mAbs) induce anti-mouse antibody responses. The objectives of the present study were to investigate whether a similar response could be seen when pigs were subjected to m-mAb therapy, and to study the kinetics of such a response. In two separate animal experiments, long-term treatment was performed with m-mAbs at low-dose levels and therapeutic levels, respectively. Two specific m-mAbs that recognized cognate antigen in the pigs (CD4 and CD8 surface antigens on T-lymphocytes) and two irrelevant control m-mAbs having no cognate antigen in the pigs were used. Enzyme-linked immunosorbent assays (ELISA) were used to quantitate the circulating m-mAbs, as well as the induced pig anti-mouse antibodies (PAMA), in serum samples from m-mAb-treated pigs. As expected, we generally saw vigorous PAMA responses within 10 days after the start of m-mAb treatment with the specific m-mAbs. However, the different mAbs showed striking differences in the kinetics and levels of PAMA responses, differences that might be ascribed to the m-mAb formulation and epitope specificity. In conclusion, treatment of pigs with m-mAbs against T-cell surface antigens induced rapid PAMA responses. This may influence and possibly decrease the effect of the m-mAb treatment by narrowing the time period where m-mAbs can efficiently be used for cell depletion.
Lohse
Louise
L
Danish Institute for Food and Veterinary Research, Department of Virology, Lindholm, Kalvehave, Denmark.
Nielsen
Jens
J
Kamstrup
Søren
S
Oleksiewicz
Martin B
MB
Eriksen
Lis
L
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000096:biosynthesis*; D000910:Antibodies, Heterophile / Q000096:biosynthesis*; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D000961:Antilymphocyte Serum / Q000008:administration & dosage; D015704:CD4 Antigens / Q000276:immunology; D016827:CD8 Antigens / Q000276:immunology; D006801:Humans; D007700:Kinetics; D008212:Lymphocyte Depletion; D051379:Mice; D013045:Species Specificity; D034421:Sus scrofa
D000888:Antibodies, Anti-Idiotypic; D000910:Antibodies, Heterophile; D000911:Antibodies, Monoclonal; D000961:Antilymphocyte Serum; D015704:CD4 Antigens; D016827:CD8 Antigens