Gaining Momentum: Kata Horváti

Peptides, like proteins, are molecules with amino acid chains. While proteins are very long and can contain hundreds of amino acids, most of the biologically active peptides consist of only a few dozen of amino acids. Over the past decades, peptide synthesis technology has developed tremendously, and producing peptides of any composition, even automatically, is no longer a problem for a researcher.

Nuggets of information for the immune system

“We can synthesise various peptides with this technology, and they can play several biological functions – says Kata Horváti – this even includes epitope peptide production. Epitopes are regions of proteins that can induce an immune response. These small units contain the essential nuggets of information for the immune system.”

Kata Horváti

For example, in the case of the SARS-CoV-2 virus that causes Covid-19 disease, certain segments of the spike proteins are such epitopes. The “certain segments” part is very important: the whole protein is not necessarily required; it is enough to find those small units that take part in the binding to the elements of the immune system.

Therefore, theoretically, these short peptides could be suitable to develop vaccines,

since if we introduce them to the body – and, at the same time, prevent them from quick degradation –, then they can help the immune system to produce antibodies, and these antibodies will be ready when the actual infection occurs with real pathogens.

Moreover, peptides have the advance over vaccines containing large proteins that multiple different peptides could be combined in a single vaccine. Then, epitopes of multiple pathogens can be “introduced” to the immune system at the same time, and therefore an immune response with a broader spectrum against the pathogen can be developed.

Possibilities

“This approach is especially interesting when we are dealing with a pathogen that is prone to change, for example, mutates rapidly, and hence can evade the immune response. It is because the chance that multiple proteins in the same pathogen can change simultaneously is low – argues Kata Horváti – Contrary to vaccines developed against a certain state of a certain pathogen, here we can combine different peptides that represent different proteins, and if necessary, we can easily change the amino acid sequence.”

As the peptide-based vaccines – similarly to the mRNA-based vaccines – are prepared by entirely synthetic methods, no biological material is present during the production process.

This would eliminate several risks that are parts of the vaccine manufacturing process based on inactivated pathogens.

In other words, no infectious agents can enter the vaccine. Therefore, there is a huge potential in peptide-based vaccines.

The current state of the technology is basically where the mRNA vaccines were before the Covid: they are being researched in many places around the world, and even phase I, II, and III trials have been initiated with some experimental peptide vaccines. These are showing promising laboratory results in cancer therapy and prevention, for example against melanoma or glioma. There is a registered peptide vaccine against Covid-19 for clinical practice. This is the EpiVacCorona, which was registered in Russia. At least the topic of the clinical trials clearly shows that the technology’s area of the application is not only viral diseases, but bacterial infections and cancer diseases too.

Kata Horváti would like to empathise that her research team will not develop another Covid vaccine, although – quite understandably – nowadays everybody associates from vaccines to the fight against coronavirus.

The goal: to develop a “vaccine platform”

“First, we are looking for vaccines against bacterial diseases, and especially against those pathogens that are resistant to conventional therapies, therefore it is hard to manage with traditional antibiotics – continues Kata Horváti. – These bacteria cause, for example, chronic pneumonia and are associated with frequent hospitalisations. One of our main targets is the causative agent of tuberculosis, as well as other, so-called ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter sp.) bacteria.”

These bacteria have developed various methods to prevent the attacks of the immune system. The bacterium of tuberculosis, for example, is able to produce molecules that prevent phagocytosis and clearance during the primary immune response following an infection. The surviving bacteria grow a thick cell wall, slow down their metabolism, and from the point of the immune system, completely change their antigenic repertoire. This new form is so different from the previous one that the immune reaction against the other form could not destroy it.

Therefore, vaccines developed against a certain phenotype are not able to neutralise all of the different forms of the bacteria. There should be a way to follow the antigen diversity resulting from these changes, for example by combining the epitopes of proteins expressed by the different forms – says Kata Horváti. However, synthesising the required peptides does not guarantee success.

“Although it is easy to synthesise epitope peptides, they are not stable enough on their own, and their immunogenicity (their potential to induce an immune response) is relatively low. Therefore, peptides should be transformed to a form where they can be used as a vaccine – explains Kata Horváti. – To do this, the peptides are modified and formulated with various chemical methods. In other words, they are transformed into their final form for use.

This means that we are providing the optimal accessibility of the peptides to the body while we are preventing their rapid degradation.”

If you simply eat the peptides, they are instantly degraded in the digestion system, and cannot be effective. On the other hand, if you wrap them into nanocapsules, or create an emulsion from them, or embed them into micelles or liposomes, that is, if you formulate them, then we can protect the molecules from rapid degradation and enhance their efficacy. A different formulation should be developed for every peptide product. At the current phase, our aim is to develop all those methods that would help the development of specific peptide vaccines in the future.

“This research will be basic research, so our aim is not to develop a specific, applicable vaccine. Our aim is to develop a technology that in the future can be used to develop vaccines against various infectious diseases– states Kata Horváti. – We will combine colloid chemistry and peptide chemistry, as this will be the way to realise our target: the development of suitable peptide formulations. In other words, we are developing a vaccine platform.”