Perinatal Immunization With Vaccine-Grade Listeria monocytogenes Provides Protection Against Murine Th2 Airway Inflammation.

Purpose: Asthma is a chronic respiratory disorder that leads to inflammation and narrowing of the airways. Its global prevalence has attained epidemic levels and treatment options that reach beyond temporary relief of symptoms are urgently needed. Since the processes leading to clinically symptomatic asthma start early in life, we set out to systematically evaluate a neonatal immunotherapeutic based on Listeria monocytogenes (Lm) for the control of allergic sensitization.

A single immunization near birth elicits immediate and lifelong protective immunity.

Most existing vaccines do not induce protective immunity immediately following birth, nor do they retain protective efficacy in the latter years of life without booster doses. Using a mouse model, we present evidence that a live-replicating vaccine administered only once shortly after birth was able to induce both immediate and lifelong protection. Newborn mice immunized with a safe, highly attenuated strain of Listeria monocytogenes (Lm) were already protected by day 7 post-vaccination when challenged with a virulent strain of Lm.

Pyruvate carboxylase plays a crucial role in carbon metabolism of extra- and intracellularly replicating Listeria monocytogenes.

The human pathogen L. monocytogenes is a facultatively intracellular bacterium that survives and replicates in the cytosol of many mammalian cells. The listerial metabolism, especially under intracellular conditions, is still poorly understood.

Neonatal immunization with Listeria monocytogenes induces T cells with an adult-like avidity, sensitivity, and TCR-Vbeta repertoire, and does not adversely impact the response to boosting.

Listeria monocytogenes (Lm) holds promise as a neonatal vaccine vehicle. Here we show that Lm immunized neonatal mice reached maximal Ag-specific CD8(+) T cell expansion after only a single immunization, while adults required two doses. Ag-specific CD4(+) T cell expansion in both age groups required a boost to reach its peak.

Fine-tuning the safety and immunogenicity of Listeria monocytogenes-based neonatal vaccine platforms.

We have developed virulence-attenuated strains of Listeria monocytogenes (Lm) that can be used as safe yet effective vaccine carriers for neonatal vaccination. Here we compare the vaccine efficacy of Lm based vaccine carrier candidates after only a single immunization in murine neonates and adults: Lm Delta(trpS actA) based strains that express and secrete multiple copies of the model antigen ovalbumin (OVA) either under the control of a phagosomal (P(hly)) or cytosolic (P(actA))-driven listerial promoter. While both strains induced high levels of antigen-specific primary and secondary CD8 and CD4 T cell responses, both neonatal and adult mice immunized with the phagosomal driven strain were significantly better protected against wildtype Lm challenge as compared to the naïve control group than mice immunized with the cytosolic driven strains.

Listeria monocytogenes as novel carrier system for the development of live vaccines.

Listeria monocytogenes is a facultative intracellular bacterium that enters a variety of non-professional mammalian cells by triggered phagocytosis ("zipper mechanism") and replicates in the cytosol of the infected host cells. Therefore, it is a promising vaccine vector for the presentation of passenger antigens to the MHC class II and especially class I pathways. Here, we review recent progress made in our laboratory on the development of novel attenuated L.

Species-specific differences in the activity of PrfA, the key regulator of listerial virulence genes.

PrfA, the master regulator of LIPI-1, is indispensable for the pathogenesis of the human pathogen Listeria monocytogenes and the animal pathogen Listeria ivanovii. PrfA is also present in the apathogenic species Listeria seeligeri, and in this study, we elucidate the differences between PrfA proteins from the pathogenic and apathogenic species of the genus Listeria. PrfA proteins of L.

Comparison of different live vaccine strategies in vivo for delivery of protein antigen or antigen-encoding DNA and mRNA by virulence-attenuated Listeria monocytogenes.

Listeria monocytogenes can be used to deliver protein antigens or DNA and mRNA encoding such antigens directly into the cytosol of host cells because of its intracellular lifestyle. In this study, we compare the in vivo efficiencies of activation of antigen-specific CD8 and CD4 T cells when the antigen is secreted by L. monocytogenes or when antigen-encoding plasmid DNA or mRNA is released by self-destructing strains of L.