Modulation of the humoral immune response by targeting CD40 and FcγRII/III; delivery of soluble but not particulate antigen to CD40 enhances antibody responses with a Th1 bias

Abstract

Targeted delivery of antigen improves immunogenicity and can obviate the use of adjuvants. In addition to molecular targeting based on affinity interactions, particle-based antigen targeting to myeloid cells is also an efficient means to enhance immune responses. We compared the efficiency of targeting a model antigen, streptavidin, to CD40 and low affinity Fc gamma receptors II and III, either in a soluble or in a particulate form. Single chain fragments targeting these receptors were used to generate soluble tetramers with streptavidin or to decorate streptavidin coated nanobeads, and mice were immunized with the different formulations. Whereas particulate presentation of streptavidin enhanced total IgG1 and IgG2a levels, overall antigen specific antibody production increased in the case of targeted soluble antigen only, as assessed by reverse protein arrays and ELISPOT. In particular, soluble CD40 targeted antigen induced the strongest IgG2a responses, suggesting a Th1 bias compared to FcgammaRII/III targeting. Combined targeting to these receptors did not further increase immunogenicity. Thus, in our model, affinity targeting of soluble antigen to CD40 proved to be superior to particle-mediated delivery both in terms of antibody quantity and quality.