Instituto de Formacion e Investigacion Marques de Valdecilla, Spain
Carmen Alvarez-Dominguez has completed his Ph.D at the age of 29 years from Universidad Autonoma de Madrid and postdoctoral studies from Washington University School of Medicine on Small GTPases role in Listeria monocytogenes phagocytosis. She is the director of the Group on Genomics, Proteomics and Vaccines at the Research Institute Marqués de Valdecilla (IFIMAV) in Santander, Spain. She has published more than 25 papers in reputed journals and serving as an editorial board member of Microbes and Infection and OMICS. She also is coauthor of the patent: Immunogenic peptides against Listeria and Mycobacterium, antibodies and their uses with reference PCT/ES2007/070144.
The use of live Listeria based vaccines shows serious difficulties to be administrated to immunocompromised individuals. However, cellular carriers present the advantage to induce a multivalent innate immunity as well as cell-mediated immune responses, constituting novel and secure vaccine strategies in listeriosis. Here, we compare the protection abilities of dendritic cells and macrophages and also their safety. We examined the immune response of these vaccine vectors using two Listeria antigens, listeriolysin O (LLO) and glyceraldehyde-3-phosphate-deshydrogenase (GAPDH) and several epitopes such as the LLO peptides, LLO189-201 and LLO91-99 and the GAPDH peptide, GAPDH1-22. We discarded macrophages as safe vaccine vectors since they show anti-Listeria protection but also high cytotoxicity. Dendritic cells loaded with GAPDH1-22 peptide conferred higher protection and security against listeriosis than the widely explored LLO91-99 peptide. Anti-Listeria protection was related with the change caused by these epitopes on dendritic cell maturation, with a high production of IL-12 as well as significant levels of other Th1 cytokines as MCP-1, TNF-a, and IFN-g and with the induction of GAPDH1-22-specific CD4+ and CD8+ immune responses. This is the first study exploring the use of a novel GAPDH antigen as a potential dendritic cell-based vaccine candidate for listeriosis, which efficiency appears to highlight the relevance of vaccine designs containing multiple CD4+ and CD8+ epitopes.