Abstract
The use of live Listeria-based vaccines carries serious difficulties when administrated to immunocompromised individuals. However, cellular carriers have the advantage of inducing multivalent innate immunity as well as cell-mediated immune responses, constituting novel and secure vaccine strategies in listeriosis. Here, we compare the protective efficacy of dendritic cells (DCs) and macrophages and their safety. We examined the immune response of these vaccine vectors using two Listeria antigens, listeriolysin O (LLO) and glyceraldehyde-3-phosphate-dehydrogenase (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 because they show anti-Listeria protection but also high cytotoxicity. DCs loaded with GAPDH1−22 peptide conferred higher protection and security against listeriosis than the widely explored LLO91−99 peptide. Anti-Listeria protection was related to the changes in DC maturation caused by these epitopes, with high production of interleukin-12 as well as significant levels of other Th1 cytokines such as monocyte chemotactic protein-1, tumor necrosis factor-α, and interferon-γ, and with the induction of GAPDH1−22-specific CD4+ and CD8+ immune responses. This is believed to be the first study to explore the use of a novel GAPDH antigen as a potential DC-based vaccine candidate for listeriosis, whose efficiency appears to highlight the relevance of vaccine designs containing multiple CD4+ and CD8+ epitopes.
Highlights
Listeria monocytogenes is a Gram-positive pathogenic bacterium that is widely used as a vector for vaccines against other pathogens or in cancer therapy
To use Bone-marrow-derived macrophages (BMDMs) and dendritic cells (DCs) as vectors loaded with pathogenic L. monocytogenes, we first discarded any differences in BMDM and DC phagocytic parameters, balancing their differentiation and maturation states
We examined whether L. monocytogenes was able to infect both cells with similar kinetics
Summary
Listeria monocytogenes is a Gram-positive pathogenic bacterium that is widely used as a vector for vaccines against other pathogens or in cancer therapy Because it is a human pathogen, it may cause life-threatening infections such as severe meningitis, encephalitis, and brain abscess in pregnant women, neonates, elderly people, and immunocompromised individuals. There is not a single ideal vector that might be considered safe for human trials, and the use of live vaccines in individuals with any type of immunosuppression poses severe difficulties. Safer vaccines such as subunit vaccines present the disadvantage of requiring strong adjuvants to potentiate their immune responses and these adjuvants might induce undesirable side effects in tissues
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