Modulation of the immune system by Listeria monocytogenes

We had previously shown that attenuated Listeria monocytogenes (Lm) vaccines induce a strong Th1 response in neonatal mice, and prophylactically protect against histopathological signs of asthma. To test the ability of Lm as a therapeutic vaccine to diminish allergic sensitization in a mouse model of ovalbumin (OVA)-induced asthma, adult mice were sensitized intraperitoneally and challenged intranasally with OVA to induce asthma. Mice were then immunized intraperitoneally with a single dose of either live attenuated Lm vaccine that expresses OVA (LmOVA), live Lm expressing no allergen, or NaCl. Six weeks later, anesthetized mice were challenged intranasally with OVA and evaluated for cellular infiltration and tissue remodeling. We found that vaccination with live-attenuated Lm strains did not reduce already established allergic inflammation in all of the parameters we measured except that it did significantly reduce the total BALF eosinophil count in the LmOVA group. To test the functional impact of our prophylactic vaccine approach in vivo, we immunized mice as newborns with live LmOVA or Lm, followed 6 weeks later by allergic sensitization with OVA and evaluation by FlexiVent to determine airway hyperreactivity. We found that prophylactic vaccination reduced airway hyperreactivity, in an antigen-specific (i.e. LmOVA) as well as non-specific (i.e. Lm not expressing OVA) manner. Thus, our neonatal prophylactic vaccine approach holds promise as a powerful tool to modulate early life immune ontogeny and effectively prevent asthma. In order to study any potentially harmful effect of neonatal immunization with Lm, newborn mice were immunized intraperitoneally with the live Lm attenuated strain or with saline. Six weeks later, anesthetized mice were challenged intranasally with Saccharopolyspora rectivirgula antigen (SR-Ag) on three consecutive days per week for three weeks. We were unable to detect any changes on the HP phenotype comparing vaccinate vs. unvaccinated mice. In conclusion, prophylactic neonatal immunization with Lm-based vaccines provided functional protection from asthma in vivo, and may also provide some therapeutic benefit. Importantly, Lm-induced early life immune modulation did not exacerbate the development of some Th1/Th17-biased diseases later in life.Medicine, Faculty ofMedicine, Department ofExperimental Medicine, Division ofGraduat