Biology subjects

Scumpia, P. O.

Publications and source records attributed to Scumpia, P. O..

4 recordsLinked to original sources

bioRxiv2024

A novel microporous biomaterial vaccine platform for long-lasting antibody mediated immunity against viral infection.

Current antigen delivery platforms, such as alum and nanoparticles, are not readily tunable, thus may not generate optimal adaptive immune responses. We created an antigen delivery platform by loading lyophilized Microporous Annealed Particle (MAP) with aqueous solution containing target antigens. Upon administration of antigen loaded MAP (VaxMAP), the biomaterial reconstitution forms an instant antigen-loaded porous scaffold area with a sustained release profile to maximize humoral immunity. VaxMAP induced CD4+ T follicular helper (Tfh) cells and germinal center (GC) B cell responses in the lymph nodes similar to Alum. VaxMAP loaded with SARS-CoV-2 spike protein improved the magnitude and duration of anti-receptor binding domain antibodies compared to Alum and mRNA-vaccinated mice. A single injection of Influenza specific HA1-loaded-VaxMAP enhanced neutralizing antibodies and elicited greater protection against influenza virus challenge than HA1-loaded-Alum. Thus, VaxMAP is a platform that can be used to promote adaptive immune cell responses to generate more robust neutralizing antibodies, and better protection upon pathogen challenge.

immunology↗

bioRxiv2022

Improved humoral immunity and protection against influenza virus infection with a 3D porous biomaterial vaccine

New vaccine platforms that properly activate humoral immunity and generate neutralizing antibodies are required to combat emerging and re-emerging pathogens, including influenza virus. Biomaterial scaffolds with macroscale porosity have demonstrated tremendous promise in regenerative medicine where they have been shown to allow immune cell infiltration and subsequent activation, but whether these types of materials can serve as an immunization platform is unknown. We developed an injectable immunization platform that uses a slurry of antigen-loaded hydrogel microparticles that anneal to form a porous scaffold with high surface area for antigen uptake by infiltrating immune cells as the biomaterial degrades to maximize humoral immunity. Antigen-loaded-microgels elicited a robust cellular humoral immune response, with increased CD4+ T follicular helper (Tfh) cells and prolonged germinal center (GC) B cells comparable to the commonly used adjuvant, aluminum hydroxide (Alum). By simply increasing the weight fraction of polymer material, we enhanced material stiffness and further increased antigen-specific antibody titers superior to Alum. Vaccinating mice with inactivated influenza virus loaded into this more highly crosslinked formulation elicited a strong antibody response and provided better protection against a high dose viral challenge than Alum. Thus, we demonstrate that by tuning physical and chemical properties alone, we can enhance adjuvanticity and promote humoral immunity and protection against a pathogen, leveraging two different types of antigenic material: individual protein antigen and inactivated virus. The flexibility of the platform may enable design of new vaccines to enhance innate and adaptive immune cell programming to generate and tune high affinity antibodies, a promising approach to generate long-lasting immunity against specific pathogens.

bioengineering↗

bioRxiv2020

Activating an adaptive immune response from a hydrogel scaffold imparts regenerative wound healing.

Biomaterial scaffolds represent a promising approach for material-based tissue regeneration. We previously developed microporous annealed particle (MAP) hydrogels - a flowable, microparticle-based hydrogel in which neighboring hydrogel particles are linked in situ to form a porous scaffold that accelerates wound healing. To promote more extensive tissue ingrowth before scaffold degradation, we aimed to slow scaffold degradation by switching the chirality of the crosslinking peptides from L-peptides to D-peptides. Unexpectedly, despite showing the predicted slower enzymatic degradation in vitro, D-peptide crosslinked MAP hydrogel (D-MAP) hastened material degradation in vivo and imparted significant tissue regeneration to healed cutaneous wounds, including increased tensile strength and hair neogenesis. By themselves, D-chiral peptides were poor activators of macrophage innate immune signaling in vivo, but MAP particles elicit IL-33 type 2 myeloid cell recruitment which is amplified in vivo in the presence of D-peptides. Remarkably, D-MAP elicited significant antigen-specific immunity against the D-chiral peptides, and an intact adaptive immune system was required for the hydrogel-induced skin regeneration. These findings demonstrate that the generation of an adaptive immune response from a biomaterial is sufficient to induce cutaneous regenerative healing despite faster scaffold degradation.

bioengineering↗

bioRxiv2017

A Macrophage Response To Mycobacterium leprae Phenolic Glycolipid Initiates Nerve Damage In Leprosy

Mycobacterium leprae causes leprosy, and is unique among mycobacterial diseases in producing peripheral neuropathy. This debilitating morbidity is attributed to axon demyelination resulting from direct interactions of the M. leprae-specific phenolic glycolipid 1 (PGL-1) with myelinating glia, and their subsequent infection. Here, we use transparent zebrafish larvae to visualize the earliest events of M. leprae-induced nerve damage. We find that demyelination and axonal damage are not directly initiated by M. leprae but by infected macrophages that patrol axons; demyelination occurs in areas of intimate contact. PGL-1 confers this neurotoxic response on macrophages: macrophages infected with M. marinum expressing PGL-1 also damage axons. PGL-1 induces nitric oxide synthase in infected macrophages, and the resultant increase in reactive nitrogen species damages axons by injuring their mitochondria and inducing demyelination. Our findings implicate the response of innate macrophages to M. leprae PGL-1 in initiating nerve damage in leprosy.

microbiology↗