The intrasplenic circulation of three formulations of the same protein antigen.

This paper presents a kinetic study of the intrasplenic circulation of three formulations of the protein antigen conalbumin including the soluble form and two liposomal formulations, one encapsulated in the internal aqueous milieu and one surface-linked to the liposomal vehicle. These formulations differ not only in their physical status but also in their immunostimulating properties and were chosen in an attempt to correlate the movements of antigen in lymphoid tissues with the immune response elicited. The presence of conalbumin was followed over a period of 21 days using, as a detection system, an antibody that we developed and which allows for the visualization of antigenic peptides such as those presented at the surface of antigen-presenting cells (APC). The results demonstrate that the amount of antigen accessing to the spleen, its time of residency and the pathway it follows are all profoundly influenced by the form under which it penetrates the immune system. The results also indicate that the marked initial preferences of an antigen for either B cells, marginal zone macrophages (MZM) or metallophilic macrophages (MM) are of fundamental importance in determining the fate of this antigen in the spleen. It is concluded that the exact formulation of an antigen is as crucial to the regulation of the immune response as is the nature of this antigen. It is further concluded that liposomes can be used efficiently to modify the formulation of an antigen and can contribute as such to the induction of specific immune functions by driving the antigen towards some privileged immune cell populations.