Year: 2023
Type: article
Abstract: Sustained release of vaccine components is a potential method to boost efficacy compared with traditional bolus injection. Here, we show that a biodegradable hyaluronic acid (HA)-scaffold, termed HA cryogel, mediates sustained antigen and adjuvant release in vivo leading to a durable immune response. Delivery from subcutaneously injected HA cryogels was assessed and a formulation which enhanced the immune response while minimizing the inflammation associated with the foreign body response was identified, termed CpG-OVA-HAC2. Dose escalation studies with CpG-OVA-HAC2 demonstrated that both the antibody and T cell responses were dose-dependent and influenced by the competency of neutrophils to perform oxidative burst. In immunodeficient post-hematopoietic stem cell transplanted mice, immunization with CpG-OVA-HAC2 elicited a strong antibody response, three orders of magnitude higher than dose-matched bolus injection. In a melanoma model, CpG-OVA-HAC2 induced dose-responsive prophylactic protection, slowing the tumor growth rate and enhancing overall survival. Upon rechallenge, none of the mice developed new tumors suggesting the development of robust immunological memory and long-lasting protection against repeat infections. CpG-OVA-HAC2 also enhanced survival in mice with established tumors. The results from this work support the potential for CpG-OVA-HAC2 to enhance vaccine delivery.
DOI: 10.1002/btm2.10591
Institution: University of California San Diego
Language: English
Subfield: Molecular Medicine
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,750
Funders: National Science Foundation, American Cancer Society, National Multiple Sclerosis Society, Multiple Sclerosis Society, National Institutes of Health, University of California, San Diego, National Heart, Lung, and Blood Institute, National Cancer Institute, National Institute of Neurological Disorders and Stroke, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Division of Electrical, Communications and Cyber Systems, National Center for Advancing Translational Sciences, School of Medicine, University of California, San Diego
Awards: G1242503956, G2928778974, G310317267, G336167305, G3968490805, G398616611, G4003527286, G4597188909, G4869303369, Cancer Researchers in Nanotechnology (CRIN), NNCI: San Diego Nanotechnology Infrastructure (SDNI), G5344493716, G5820425362, Biomaterial scaffold-assisted drug delivery to modulate acute graft-versus-host-disease, University of California San Diego Neuroscience Microscopy Imaging Core, G639426234, G6948496559, G70231108, G7091389010, UC San Diego Clinical and Translational Research Institute, G8021374757, G8375898738, G8711730408, G8734224423, G9000028825, G9000120855, G9000127217, G9000222291, G909366919
OpenAlex ID: W4386069290