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

Abstract

Listeria monocytogenes is a foodborne intracellular bacterial pathogen leading to human listeriosis. Despite a high mortality rate and increasing antibiotic resistance no clinically approved vaccine against Listeria is available. Attenuated Listeria strains offer protection and are tested as antitumor vaccine vectors, but would benefit from a better knowledge on immunodominant vector antigens. To identify novel antigens, we screened for Listeria epitopes presented on the surface of infected human cell lines by mass spectrometry-based immunopeptidomics. In between more than 15,000 human self-peptides, we detected 68 Listeria epitopes from 42 different bacterial proteins, including several known antigens. Peptide epitopes presented on different cell lines were often derived from the same bacterial surface proteins, classifying these antigens as potential vaccine candidates. Encoding these highly presented antigens in lipid nanoparticle mRNA vaccine formulations resulted in specific CD8+ T-cell responses and high levels of protection in vaccination challenge experiments in mice. Our results pave the way for the development of a clinical mRNA vaccine against Listeria and aid to improve attenuated Listeria vaccines and vectors, demonstrating the power of immunopeptidomics for next-generation bacterial vaccine development.

The Promising Potential of Reverse Vaccinology-Based Next-Generation Vaccine Development over Conventional Vaccines against Antibiotic-Resistant Bacteria

“…The use of an adjuvant led to the activation of invariant natural killer T (iNKT) cells and specific T cell responses. Experiments showed that immunization with the top vaccine candidate, LMON_0149, was able to confer protection in mice when challenged with L. monocytogene due to the elicitation of strong cellular immune responses [87]. Kon et al (2022) reported the development of an mRNA lipid nanoparticle (mRNA-LNP) vaccine against the plague, a highly infectious disease caused by the Gram-negative bacterium Yersinia pestis [88].…”

“…The use of an adjuvant led to the activation of invariant natural killer T (iNKT) cells and specific T cell responses. Experiments showed that immunization with the top vaccine candidate, LMON_0149, was able to confer protection in mice when challenged with L. monocytogene due to the elicitation of strong cellular immune responses [ 87 ].…”