Ricardo Calderon-Gonzalez, Elisabet Frande-Cabanes, Raquel Tobes, Eduardo Pareja, Lidia Alaez-Alvarez and Carmen Alvarez-Dominguez
Objective: Individuals at risk of Listeria infection lacked vaccines to prevent the development of severe listeriosis symptoms. Here, we identify the best epitopes from Listeria proteins GAPDH and LLO for an optimal DC vaccine candidate to protect against individuals high susceptible to listeriosis.
Methods: We vaccinated high susceptible Balb/c and low susceptible C57BL/6 mice with a single dose of DC-LLO91-99, DC-LLO189-200, DC-LLO190-201, DC-LLO189-201, DC-LLO296-304, DC-GAPDH1-15 or DC-GAPDH1-22 vaccines. CFU in spleens, predictions of DC- peptide binding to MHC-I and MHC-II and analysis of Th1 immune responses were used to assess vaccine efficiency.
Results: DC-GAPDH1-22 and DC-GAPDH1-15 vaccines with intermediate binding epitopes to MHC-I and weak binders to MHC-II, provided maximal protection in Listeria susceptible and resistant mice. DC-LLO91-99 vaccine with a strong binding epitope to MHC-I follows protection in both mice strains. DC-LLO296-304 vaccine conferred protection only in resistant mice and DC-LLO190-201, DC-LLO189-200 and DC-LLO189-201 vaccines with binding epitopes to MHC-II, lacked protection properties. Maximal protection in listeriosis correlated with increased splenic CD8α+ DC, enhanced IL-12 production and high frequencies of CD8+ and CD4+ producing IFN- T cells in both mice strains.
Discussion: Maximal protection against listeriosis in susceptible and resistant mice is only achieved with DC-GAPDH1-22 and DC-GAPDH1-15 vaccines, able to activate simultaneously CD4+ and CD8+ T cells as they include binding epitopes to both, MHC-I and MHC-II. CD8+ T cell activation seemed predominant as DC-LLO91-99 and DC-LLO296-304 vaccines that exclusively activate CD8+ T cells in both mice strains conferred significant listeriosis protection. In this regard, DC-LLO189-201, DC-LLO189-200 or DC-LLO190-201 vaccines that activated CD4+ T cells caused no protection at all. We observed that a combination of several MHC-I and at least one MHC-II binding epitopes in a single peptide provided the highest listeriosis protection.
Conclusion: DC-GAPDH1-22 and DC-GAPDH1-15 vaccines might protect against human listeriosis in high susceptible immune-compromise patients.