| Institution: | 1. Iowa State University, Department of Veterinary Microbiology and Preventative Medicine, United States;2. Iowa State University, Department of Chemical and Biological Engineering, United States;3. Iowa State University, Department of Kinesiology, United States;4. Nanovaccine Institute, Iowa State University, United States;1. University of North Florida, Department of Biological Sciences, 1 UNF Drive, Jacksonville, FL 32224, USA;2. The Marine Mammal Center, Marin Headlands, 2000 Bunker Road, Fort Cronkhite, Sausalito, CA 94965, USA;1. Department of Animal Genetics, Center for Research in Agricultural Genomics (CSIC-IRTA-UAB-UB), Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain;2. Departament de Ciència Animal i dels Aliments, Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain;3. Departamento de Ciencias Agroforestales, Escuela Universitaria de Ingeniería Técnica Agrícola-Universidad de Sevilla, Carretera Utrera, km. 1, 41013 Sevilla, Spain;4. Instituto Murciano de Investigación y Desarrollo Agrario y Alimentario (IMIDA), Estación Sericícola, La Alberca, Murcia, Spain;5. Departamento de Producción Animal, Campus de Rabanales, Universidad de Córdoba, 14071 Córdoba, Spain;1. State Key Laboratory of Virology & Key Laboratory of Analytical Chemistry for Biology and Medicine (MOE), College of Chemistry and Molecular Sciences, Wuhan University, Wuhan, 430072, PR China;2. Department of Clinical Laboratory, Zhongnan Hospital, Wuhan University, Wuhan, 430071, PR China;1. Centre for Cancer and Inflammation Research, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong, China;2. Consun Chinese Medicines Research Centre for Renal Diseases, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong, China;3. Research and Development Centre for Natural Health Products, HKBU Shenzhen Research Institute and Continuing Education, Shenzhen, Hong Kong, China;4. JaneClare Transdermal TCM Therapy Laboratory, Hong Kong Baptist University, Hong Kong, China |
| Abstract: | BackgroundOne of the most concerning public health issues, related to vaccination and disease prevention, is the inability to induce durable immune responses following a single-dose immunization. In this regard, the nature of the inflammatory environment induced by vaccine adjuvants can negatively impact the resulting immune response. To address these concerns, new strategies to vaccine design are needed in order to improve the outcomes of immune responses, particularly in immunologically disadvantaged populations.MethodsComparisons of the scope of innate immune activation induced by TLR agonists versus cyclic dinucleotides (CDNs) was performed. Their effects on the activation characteristics (e.g., metabolism, cytokine secretion) of bone marrow derived dendritic cells (BMDCs) were studied. In addition, the differential effects on in vivo induction of antibody responses were measured.ResultsAs compared to TLR ligands, the stimulation of BMDCs with CDNs induced distinctly different metabolic outcomes. Marked differences were observed in the production of nitric oxide (NO) and the cytokine BAFF. These distinct differences were correlated with improved (i.e., more rapid and persistent) vaccine antibody responses in both aged and young mice.ConclusionsOur results illustrate that the innate immune pathway targeted by adjuvants can critically impact the outcome of the immune response post-vaccination. Specifically, CDN stimulation of APCs induced an activation phenotype that was characterized by decreased innate effector molecule production (e.g., NO) and increased BAFF. This was attributed to the induction of an innate inflammatory environment that enabled the host to make the most of the existing B lymphocyte potential. The use of adjuvants that differentially engage mechanisms of innate immune activation would be particularly advantageous for the generation of robust, single dose vaccines. The results of this study demonstrated that CDNs induced differential innate activation and enhanced vaccine induced antibody responses in both young and aged mice. |
