Affiliation:
1. Department of Nanoengineering University of California San Diego La Jolla California USA
2. Chemical Engineering Program University of California San Diego La Jolla California USA
Abstract
AbstractSustained 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.
Funder
American Cancer Society
National Cancer Institute
National Heart, Lung, and Blood Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases
National Multiple Sclerosis Society
Subject
Pharmaceutical Science,Biomedical Engineering,Biotechnology
Cited by
1 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献