Polymeric Multilayer Capsule-Mediated Vaccination Induces Protective Immunity Against Cancer and Viral Infection

Abstract

Recombinant antigens hold high potential to develop vaccines against lethal intracellular pathogens and cancer. However, they are poorly immunogenic and fail to induce potent cellular immunity. In this paper, we demonstrate that polymeric multilayer capsules (PMLC) strongly increase antigen delivery toward professional antigen-presenting cells in vivo, including dendritic cells (DCs), macrophages, and B cells, thereby enforcing antigen presentation and stimulating T cell proliferation. A thorough analysis of the T cell response demonstrated their capacity to induce IFN-γ secreting CD4 and CD8 T cells, in addition to follicular T-helper cells, a recently identified CD4 T cell subset supporting antibody responses. On the B cell level, PMLC-mediated antigen delivery promoted the formation of germinal centers, resulting in increased numbers of antibody-secreting plasma cells and elevated antibody titers. The functional relevance of the induced immune responses was validated in murine models of influenza and melanoma. On a mechanistic level, we have demonstrated the capacity of PMLC to activate the NALP3 inflammasome and trigger the release of the potent pro-inflammatory cytokine IL-1β. Finally, using DC-depleted mice, we have identified DCs as the key mediators of the immunogenic properties of PMLC.

Hollow microneedle-mediated intradermal delivery of model vaccine antigen-loaded PLGA nanoparticles elicits protective T cell-mediated immunity to an intracellular bacterium

“…Delivery of vaccine protein antigens over the cellular membrane can be achieved using delivery systems and over the past decades different types of them, such as polymeric nanoparticles, emulsions and lipid-based nanoparticles have been developed [10][11][12]. Nano-encapsulation of antigens has several advantages, such as stabilization of antigens in vivo, enhancement of the uptake by pAPC and also reduction of antigen release into systemic circulation [4,13]. The immune outcome can be potentially shaped by using nanoparticles with difference size [14] and surface charge [15], and by co-encapsulating antigen and adjuvant into the nanoparticles [16,17].…”

pH-Degradable Mannosylated Nanogels for Dendritic Cell Targeting

“…[14][15][16] Relative to soluble antigens, antigens formulated as nanoparticles promote cross-presentation to CD8 + T-cells that can differentiate into cytotoxic T-cells that can recognize and eliminate infected and malignant cells. [16][17][18][19][20][21][22] Furthermore, ligating immune-stimulatory small molecules to supramolecular structures should reduce systemic levels and confine the inflammatory activity to lymphatic tissues. 23,24 Although, the synthesis of mannosylated polymers and nanoparticle derived thereof has been extensively reported 7,[25][26][27] and explored for DC targeting 28,29 , the efficacy of unambiguously targeting the mannose receptor CD206 on DCs remains elusive.…”

Nanoporous polyelectrolyte vaccine microcarriers. A formulation platform for enhancing humoral and cellular immune responses

“…These findings prompted us at using a mannitol/DS/ P L ARG/OVA ratio of 200/20/25/5 for further experiments. Interestingly, this ratio is very similar to the ratio of polyelectrolytes and antigen applied to yield hollow Layer-by-Layer [17] capsules [18][19][20][21] where porous calcium carbonate microparticles are loaded with OVA and subsequently coated with alternating layers of dextran sulfate and poly-L-arginine followed by dissolution of the calcium carbonate core templates [22][23][24][25][26][27]. Evidently, in the present work the single calcium carbonate pore former [28] (which creates capsules with a hollow void) is replaced by mannitol that creates a nanoporous internal structure as earlier reported.…”