Porcine humoral immune responses to multiple injections of murine monoclonal antibodies

Authors: LOHSE, LOUISE; NIELSEN, JENS; KAMSTRUP, SØREN1; OLEKSIEWICZ, MARTIN B.2; ERIKSEN, LIS3

Source: Apmis, Volume 113, Numbers 7-8, August 2005 , pp. 489-496(8)

Publisher: Wiley-Blackwell

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Abstract:

Lohse L, Nielsen J, Kamstrup S, Oleksiewicz MB, Eriksen L. Porcine humoral immune responses to multiple injections of murine monoclonal antibodies. APMIS 2005;113:489–96.

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.

Keywords: CD4; CD8; ELISA; IgG; anti-mouse response; immunoglobulin; immunotherapy; mAb; pig

Document Type: Research Article

DOI: http://dx.doi.org/10.1111/j.1600-0463.2005.apm_62.x

Affiliations: 1: Danish Institute for Food and Veterinary Research, Department of Virology, Kalvehave, 2: Novo Nordisk A/S, Applied Trinomics, Måløv and 3: Royal Veterinary and Agricultural University, Department of Farm Animals and Horses, Copenhagen, Denmark

Publication date: August 1, 2005

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