The purpose of this dissertation is to investigate the use of novel polymeric nanomaterials for modulation of the humoral immune system. I focus on developing materials for targeted antigen delivery in order to alter the subsequent antigen-specific antibody response. The precise control of antigen-specific responses has translational potential to improve both vaccination and tolerance-inducing therapeutics. In Chapter 1, I review the immune pathways involved in mounting an antibody response including the roles of antigen presenting cells (APCs), T cell and B cells. I introduce the fields of vaccination and antigen-specific tolerance and highlight the open questions involving antigen delivery and recognition by the immune system, and highlight the value of engineered nanomaterials as tools for better understanding and controlling these responses. In Chapter 2, I build upon previous work and engineer APC-targeted polymersomes for use as a COVID-19 vaccine. Using the receptor binding domain (RBD) of the SARS-CoV-2 spike protein as the target antigen, I formulate RBD-encapsulated (RBDencap) and RBD-surface decorated (RBDsurf) polymersomes for co-administration with adjuvanting monophosphoryl-lipid A (MPLA)-encapsulated polymersomes. I analyze the resulting immune response to vaccination and compare the effects of encapsulated and surface-bound delivery of RBD and find that vaccination with RBDsurf alone elicited strong neutralizing IgG responses as well as RBD-specific CD8+ T cell responses. In Chapter 3, I present a mannose glycopolymer conjugate (p(Man)) for increased antigen delivery to the tolerogenic microenvironment of the liver. I investigate the effects of p(Man)-antigen delivery on antigen-specific T and B cell responses. Using uricase as a model immunogenic therapeutic, I demonstrate the capacity of p(Man)-uricase pre-treatment to reduce the uricase-specific antibody response upon future antigen experience. Lastly, I probe the effects of antigen post-translational glycosylation on p(Man)-antigen treatment and discuss the use of the Uox-/- mouse as a potential model of anti-drug antibody-mediated loss of therapeutic efficacy. In Chapter 4, I discuss the conclusions and future directions of both projects and open questions in the fields of vaccination and antigen-specific humoral tolerance. Lastly, I will present a forward-looking summary of the future of nanomaterials for antigen delivery.