mRNA vaccines against bacteria: Listeria shows the way
The development of a Listeria vaccine opens a route to producing mRNA vaccines against other bacterial infections.
Ghent, 17 October – The bacterium Listeria monocytogenes can lead to listeriosis after eating contaminated food. In some people, listeriosis causes sepsis and meningitis. It is rare but lethal. Around 20 – 30% of infected people don’t survive. The team of Prof. Francis Impens (VIB-UGent Center for Medical Biotechnology), together with colleagues at Ghent University, Cancer Research Institute Ghent, and other researchers, takes an important step towards a Listeria vaccine. Combining innovative antigen discovery and mRNA vaccine technologies, the study paves the way to develop much-needed vaccines against other bacteria.
Food and listeriosis
Meat products and unpasteurized cheese are the preferred breeding ground for Listeria monocytogenes. Upon infection, pregnant women, the elderly, and immunocompromised people are at risk of developing listeriosis. This happens when the Listeria bacteria cross the intestinal barrier and reach the lymph nodes. From there, into the bloodstream it goes, and the problems begin. The bacterium tends to prefer going to the liver and spleen, but it can also cross the blood-brain barrier or make its way to the fetus in pregnant women.
The travels of Listeria in the body can lead to complications such as invasive gastroenteritis, sepsis, encephalitis, meningitis, endocarditis, or abortion. Because the bacterium can grow at refrigerator temperatures, it is one of the reasons we need stringent control and hygiene measures in the food industry. Antibiotic resistance is also a rising concern when it comes to listeriosis. Ideally, we'd have better protection. A vaccine, for example.
Finding peptides
To make a vaccine, we first need antigens. These bacterial molecules activate the immune system and kickstart the production of cells and antibodies that attack the infection. There is a problem with Listeria, though. It hides inside human cells from the immune system.
Dr. Rupert Mayer, first author of the study, says: “Listeria can invade and replicate inside the cells of our body. For this reason, it is particularly difficult to identify the Listeria antigens that are recognized by the immune system. This is a general problem with intracellular bacteria and has made vaccine development against such pathogens notoriously difficult”.
Fortunately, our cells display little bits of bacteria on their surface when they are infected. Human cells are covered in so-called self-peptides, short protein fragments that signal to the immune system 'don't attack us, we're part of the body.' When a bacterium infects a cell, some bacterial peptides are also expressed on the cell surface. It's a matter of finding them.
That's what the team of Prof. Francis Impens and colleagues did. With advanced mass spectrometers at the VIB Proteomics Core, the researchers detected over 15,000 peptides on infected human cells. Eventually, they detected 68 Listeria peptides, including several with antigenic properties.
Time for a test
The team selected Listeria antigens that were present on different types of human cells and with help from Dr. Ine Lentacker and her team at Ghent University, these antigens were encoded in an mRNA vaccine, well-known from the coronavirus pandemic. Testing the vaccine in mice led to a specific immune response and induced protection against listeriosis. This work can be the basis for a human vaccine as well as a livestock vaccine, since Listeria can cause significant problems for infected animals in that sector.
Francis Impens: “Beyond protecting humans, a Listeria vaccine for farm animals could result in safer food and increased animal health. Our study also shows the potential to develop much-needed vaccines against other intracellular bacteria, such as Salmonella, Shigella, or Mycobacterium tuberculosis. Powerful mass spectrometry-based discovery of antigens combined with the flexibility of the mRNA vaccine technology can drastically speed up vaccine development. This is good news as antibacterial vaccines are one of the solutions to tackle the fast-rising problem of antibiotic resistance.”
Immunopeptidomics-based design of mRNA vaccine formulations against Listeria monocytogenes. Mayer et al. Nat Comms, 2022.
Gunnar De Winter
Joran Lauwers
