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.