α2-macroglobulin co-administered in vivo promotes antigen delivery and presentation

Administered in vivo, covalent receptor-recognized α2-macroglobulin (α2M)-antigen complexes enhance humoral and cell-mediated immunity. We hypothesized that in vivo α2M-encapsulation could be promoted in the setting of vaccines that co-deliver α2M with unbound antigen, thereby eliminating the need to prepare complexes in vitro. Mice immunized intradermally with co-delivered α2M and OVA demonstrated antigen-specific immune responses, including anti-tumor responses, similar to those elicited by conjugated α2M-OVA complexes. Enhanced immunity appears to result from in vivo α2M-encapsulation of antigen. This finding represents a significant advancement in the development of α2M as an antigen delivery vehicle capable of enhancing the presentation of subunit vaccines.