Pathogen-associated molecular patterns on biomaterials: a paradigm for engineering new vaccines

Abstract

Vaccine development has progressed significantly and has moved from whole microorganisms to subunit vaccines that contain only their antigenic proteins. Subunit vaccines are often less immunogenic than whole pathogens; therefore, adjuvants must amplify the immune response, ideally establishing both innate and adaptive immunity. Incorporation of antigens into biomaterials, such as liposomes and polymers, can achieve a desired vaccine response. The physical properties of these platforms can be easily manipulated, thus allowing for controlled delivery of immunostimulatory factors and presentation of pathogen-associated molecular patterns (PAMPs) that are targeted to specific immune cells. Targeting antigen to immune cells via PAMP-modified biomaterials is a new strategy to control the subsequent development of immunity and, in turn, effective vaccination. Here, we review the recent advances in both immunology and biomaterial engineering that have brought particulate-based vaccines to reality.

Targeting human dendritic cells via DEC-205 using PLGA nanoparticles leads to enhanced cross-presentation of a melanoma-associated antigen

“…The particulate nature of these delivery vehicles permits their rapid internalization by DCs and their composition can provide adjuvant properties required for immunogenicity. 18 Ag encapsulated in NPs and targeted to APC are protected from enzymatic degradation, and processed and presented to T lymphocytes after their delivery to the APC.…”

“…16,17 Moreover, the particulate nature of these systems permits their rapid internalization by DCs, perhaps due to their pathogen-mimicking size and charge profile, an effect that can be heightened by surface decoration of NPs with defined PAMP. 18 However, comparatively little is known about whether immune responses induced by NPs can be further enhanced by directing Ag-containing NPs via cell surface lectin receptors such as DEC-205 to human monocyte-derived DCs, the principal cell type utilized clinically in antitumor vaccination. It is understood that the presence and density of anti-DEC-205 on NPs in the mouse system can enhance a vaccine response, 19 but outside of recent targeting of plasmacytoid DCs as APC, 9 very little is known regarding the efficiency of this targeted approach and its mechanistic impact on cross-presentation in human DC populations.…”

Hepatitis C virus E2 protein encapsulation into poly D, L-lactic-<em>co</em>-glycolide&nbsp;microspheres could induce mice cytotoxic T-cell response

“…The particulate nature of PLGA particles performed a rapid internalization, perhaps because of its pathogen-mimicking size and charge profile. 28 The studies by Newman et al 29 showed that PLGA particles are able to induce and enhance immune responses of poor immunogens. For a viral vaccine, this very interesting study showed that HIV p24 protein adsorbed onto the surface of surfactant-free anionic poly(d,l-lactide) or poly lactic acid nanoparticles was efficiently taken up by mouse dendritic cells, inducing the maturation of dendritic cells.…”

“Wrapped Up” Vaccines in the Context of HIV-1 Immunotherapy

“…Moreover, the nature of non-viral carriers allows their functionalization with moieties permitting specific targeting to DCs. Additionally they allow co-delivery of immunostimulatory molecules which can direct the immune system toward the humoral or cellular arm [181]. The simultaneous delivery of antigens and immune-stimulators to the same DC is a feature which has been reported to significantly augment the strength of the induced adaptive immune responses [182][183][184].…”