New generation vaccines offer promises of more specific immune protection and less adverse effects when compared to traditional vaccines. In contrast to traditional vaccines that are primarily consisted of live attenuated or inactivated whole pathogens and toxins, numerous new vaccines under development are composed of synthetic, recombinant, or highly purified subunit antigens. While these subunit antigens do not contain as much components as whole pathogens to cause side effects, they are also likely less immunogenic. Therefore, there is an urgent need for the development of new and improved vaccine adjuvants. Even though hundreds of agents have been listed as having adjuvant activity when used in animal models, aluminum salt-based adjuvant remains to be the sole agent used in U.S.-licensed vaccines. Pattern recognition molecules represent a novel class of candidates for adjuvant development. Pattern recognition molecules expressed intracellularly, extracellularly, or on cell surface recognize pathogen-associated molecular patterns (PAMPs) and play critical roles in the initiation of innate and adaptive immune responses. The extracellular matrix (ECM) protein Mindin is a pattern recognition molecule that may function as a molecular adjuvant in vaccination. Mindin belongs to the F-spondin family of ECM proteins and is highly conserved across species. Our results demonstrate that Mindin plays a key role in the initiation of innate and adaptive immune responses. Importantly, Mindin can amplify the inflammatory response to PAMPs stimulation and enhance phagocytosis of bacteria by normal macrophages. These properties of Mindin suggest that it can enhance immune responses to microbial pathogens. In this application, we propose to examine whether Mindin can be used as a molecular adjuvant for bacterial and viral vaccines. First, Mindin will be purified and used as an adjuvant in immunizations with influenza virus and group B Streptococcus vaccines. Second, Mindin will be fused to vaccine subunits or capsular polysaccharides and the conjugated products will be tested in immunizations. Third, Mindin fused DNA plasmids will be examined for their efficacy in protecting influenza virus infection. ? ?
| Li, Yili; Cao, Chunzhang; Jia, Wei et al. (2009) Structure of the F-spondin domain of mindin, an integrin ligand and pattern recognition molecule. EMBO J 28:286-97 |
| Jia, Wei; Li, Hong; He, You-Wen (2008) Pattern recognition molecule mindin promotes intranasal clearance of influenza viruses. J Immunol 180:6255-61 |
| Wang, Qing-Qing; Li, Hong; Oliver, Tim et al. (2008) Integrin beta 1 regulates phagosome maturation in macrophages through Rac expression. J Immunol 180:2419-28 |
| Li, Hong; Oliver, Tim; Jia, Wei et al. (2006) Efficient dendritic cell priming of T lymphocytes depends on the extracellular matrix protein mindin. EMBO J 25:4097-107 |
