Delivery of antigens to antigen presenting cell surface receptors represents a promising strategy to improve immune response to weak immunogenic antigens. We have analyzed the potential of porcine sialoadhesin (Sn) and CD163 as antigen targeting receptors using mouse Igs as surrogate antigens. Sn and CD163 are two endocytic receptors mainly expressed on macrophages located in antigen-sampling zones of secondary lymphoid organs. MAbs to CD163 induced in vitro PBMC proliferation at concentrations 50-80 fold lower than the control mAb when using, as responder cells, cells from pigs immunized with mouse serum IgGs. To evaluate in vivo targeting, pigs were immunized s.c. with anti-Sn, anti-CD163 or control mAbs, and the immune response induced to mouse Ig was analyzed. Two weeks after the first immunization, pigs receiving either anti-Sn or anti-CD163 mAbs started to show higher anti-mouse-IgG serum titres than controls. Boosting 6 weeks later, further increased the anti-IgG titres up to 15-60 fold those of controls. In addition, differences in the relative predominance of IgG1 or IgG2 subclasses in the response depending on Sn or CD163 targeting were observed. Peripheral blood mononuclear cells from pigs immunized with anti-Sn mAb showed a higher proliferative response to mouse IgG than cells from pigs immunized with control mAb. These results show that targeting antigen to Sn or CD163 can enhance the immune response in pigs.