Abstract
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.
Highlights
Previous studies have demonstrated that antigen encapsulation by α2-macroglobulin (α2M)1 enhances antigen-specific immune responses, both in vitro and in vivo [1,2,3,4,5,6,7]
Α2M-encapsulated antigen complexes were typically prepared by in vitro incubation of amine-activated α2M, designated α2M*, with an 8 to 100-fold-molar excess of antigen in the presence of heat [3,4,7]. These α2M*-antigen complexes were purified by size-exclusion chromatography to remove unbound antigen
We investigate the ability of α2M*, co-administered with unbound antigen, to enhance antigen-specific immune responses through in vivo encapsulation, resulting in enhanced antigen delivery
Summary
Previous studies have demonstrated that antigen encapsulation by α2-macroglobulin (α2M) enhances antigen-specific immune responses, both in vitro and in vivo [1,2,3,4,5,6,7]. For these studies, α2M-encapsulated antigen complexes were typically prepared by in vitro incubation of amine-activated α2M, designated α2M*, with an 8 to 100-fold-molar excess of antigen in the presence of heat [3,4,7]. We investigate the ability of α2M*, co-administered with unbound antigen, to enhance antigen-specific immune responses through in vivo encapsulation, resulting in enhanced antigen delivery
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