IDIVAL patents a multivalent vaccine against listeriosis tuberculosis and pneumonia

2 de September de 2019

After the last outbreak of listeriosis occurred in Spain, the bacterium Listeria monocytogenes, has established itself in Spain as one of the pathogens causing more virulent food infections. In general, immunocompromised individuals are those with a high risk of listeriosis, either due to natural immunosuppression such as pregnancy, newborns or the elderly, or due to pathological immunosuppression such as cancer patients, autoimmune patients, with conditions liver or kidney, patients undergoing treatment with immunosuppressants or patients with AIDS.

Against this infection, the Valdecilla Biomedical Research Institute (IDIVAL) has patented a multivalent synthetic vaccine effective not only in the treatment and / or prevention of listeriosis, but also for tuberculosis and pneumonia. Patented therapeutic vaccines consist of gold glyconanoparticles conjugated to peptides 1-15 of glyceraldehyde-3-phosphate dehydrogenase (GAPDH1-15) of various bacterial genera. The vaccine is in a pre-clinical phase and has been tested in mice.

The project has been selected to participate in the 17th Pharmaceutical Industry Day on October 29.

The principal researcher, Dr. Carmen Álvarez Domínguez, tells us the most relevant aspects of the project:

What is the vaccine?

It is a synthetic vaccine formed by very small gold nanoparticles of 2 nanometers, which have two compounds coupled by a very stable chemical bond, a short 15 amino acid peptide of a bacterial protein with enzymatic action, glyceraldehyde-3-phosphate dehydrogenase or GAPDH and also carry a carbohydrate, beta-D-glucose, GNP-GAPDH1-15 nanovaccines. These nanovaccines have low toxicity, are very homogeneous in size and the peptide coupled in them cannot be easily degraded, having a very long half-life. This peptide belongs to a bacterial virulence factor and its sequence and structure is the same in three bacterial genera, Listeria, Mycobacterium and Streptococcus.

What is your mecanism of action?

These GNP-GAPDH1-15 nanovaccines target the cells responsible for starting the immune response, dendritic cells, and as the structure of the GAPDH1-15 peptide is very similar in the three bacterial genera, Listeria, Mycobacterium and Streptococcus, they have the ability to multivalent vaccine, that is, able to protect against infections of pathogenic strains of the three bacterial genera, simultaneously. Specifically, we have seen that it protects against experimental models of listeriosis, cutaneous and pulmonary mycobacteria and streptococcal pneumonia, both in adult and elderly models, and in the case of listeriosis, it also protects in neonatal infection models.

What are the next steps so that the vaccine can become a reality and can be used in humans?

To examine whether the vaccine formulation induces a specific immune response using blood cells from both patients with listeriosis, as well as with mycobacterial lungs and skin, as well as with streptococcal pneumonia, compared to healthy individuals. Prepare the formulation on a large scale with the help of an expert pharmacist under GMP conditions, that is, good manufacturing practices, and carry out pharmacokinetic studies to assess its safety and specific protective capacity in immunodeficient mouse models, with the objective to be able to send a request for a clinical trial in Phase 1 to the European medicine agency and assess its toxicity and safety in healthy donors. From here, if the vaccine is safe, its ability to induce a specific response in healthy individuals and in different high-risk groups to these pathogens could be tested.