A model shed antigen, ovalbumin (OVA), was incorporated into polymeric biomaterial carriers made of poly(lactic-co-glycolic acid) (PLGA) in the form of microparticles (MP) or scaffolds (SC). These polymeric biomaterial carrier vehicles with incorporated antigen were then injected or implanted into mice and the resulting time-dependent systemic humoral immune response towards the controlled released OVA was assessed by following the OVA-specific IgG concentration and isotypes using ELISA. To assess the differential level of enhancement of the immune response depending on the form of carrier vehicle (MP vs. SC), the total amount of polymer and OVA delivered was kept constant as well as the release rate of OVA for both carrier vehicles. The level of the humoral immune response was higher and sustained for OVA released from PLGA SC which were implanted with associated tissue damage, and lower and transient when the same amount of polymer and OVA were delivered from PLGA MP, which were minimally invasively delivered by injection. This immune response was primarily Th2 helper T cell-dependent, although for the strong adjuvant, CFA, and PLGA SC carriers there was both a Th2 and Th1 response contribution. These results implicate 'danger signals' associated with the implantation of the scaffolds due to tissue injury which primed the system for an enhanced immune response.