A Cross-Protective Vaccine Against 4b and 1/2b Listeria monocytogenes

Abstract

Listeria monocytogenes (Lm) is a foodborne zoonotic pathogen that causes listeriosis with a mortality rate of 20–30%. Serovar 4b and 1/2b isolates account for most of listeriosis outbreaks, however, no listeriosis vaccine is available for either prophylactic or therapeutic use. Here, we developed a triple-virulence-genes deletion vaccine strain, and evaluated its safety, immunogenicity, and cross-protective efficiency. The virulence of NTSNΔactA/plcB/orfX was reduced 794-folds compared with the parental strain. Additionally, it was completely eliminated in mice at day 7 post infection and no obvious pathological changes were observed in the organs of mice after prime-boost immunization for 23 days. These results proved that the safety of the Lm vaccine strain remarkably increased. More importantly, the NTSNΔactA/plcB/orfX strain stimulated higher anti-Listeriolysin O (LLO) antibodies, induced significantly higher expression of IFN-γ, TNF-α, IL-17, and IL-6 than the control group, and afforded 100% protection against serovar 4b and 1/2b challenges. Taken together, our research demonstrates that the triple-genes-deletion vaccine has high safety, can elicit strong Th1 type immune response, and affords efficient cross-protection against two serovar Lm strains. It is a promising vaccine for prevention of listeriosis.

Immunopeptidomics-based design of highly effective mRNA vaccine formulations againstListeria monocytogenes

“…In comparison to clinically more problematic intracellular bacteria such as Mycobacterium tuberculosis, Listeria is relatively easy to cultivate and safe to work with and is therefore often used as a model system for intracellular bacterial infections 3 . So far mostly live attenuated vaccines against Listeria have been explored, typically resulting in high levels of protection in animal models [24][25][26]29,30 . Similarly, inactivated Listeria or bacterial ghosts (bacteria depleted of intracellular content) were explored as preclinical vaccine candidates 31,32 .…”

Immunopeptidomics-based design of mRNA vaccine formulations against Listeria monocytogenes

“…So far mostly live attenuated vaccines against Listeria have been explored, typically resulting in high levels of protection in animal models [24][25][26]29,30 . Similarly, inactivated Listeria or bacterial ghosts (bacteria depleted of intracellular content) were explored as preclinical vaccine candidates 31,32 .…”