Malaria research has taken a valuable step forward, starting from Ticino, thanks to a study coordinated by Dr. Caroline Junqueira ofInstitute for Research in Biomedicine (IRB) of Bellinzona, affiliated with theUniversity of Italian Switzerland (USI). The work, published in the scientific journal Nature, has identified a new set of antigens from the parasite responsible for malaria that could represent an important basis for the development of vaccines capable of offering broader and longer-lasting protection than those currently available.
The study addresses one of the major obstacles in malaria vaccine research: the identification of targets recognized by CD8+ T lymphocytes, immune system cells capable of identifying and destroying cells infected by the parasite.
A detailed map of the parasite's antigens
To achieve this, the researchers used immunopeptidomics, a methodology that integrates immunology and proteomics to identify protein fragments exposed on the surface of infected cells and presented to the immune system.
The analysis allowed us to identify 453 unique peptides attributable to 166 proteins of PlasmodiumAmong these, 75 belong to the so-called housekeeping proteins, elements essential for the survival of the parasite and characterised by a high level of conservation among the different species of Plasmodium.
This is a particularly interesting feature from a vaccine perspective, since these proteins are expressed at multiple stages of the parasite's life cycle, both during the liver and blood phases.
Why the discovery is important
One of the limitations of vaccines available today is their incomplete and time-limited protection. The formulations currently used are in fact concentrated primarily against Plasmodium falciparum, the species responsible for most cases of malaria in Africa, and act mainly in the very early stages of infection.
The IRB study instead suggests the possibility of developing vaccines capable of targeting antigens shared between different species of Plasmodium and present in multiple stages of infection. This could translate, in perspective, into a broader and more stable immune response.
The role of CD8+ T lymphocytes
The research focuses on the activation of CD8+ T lymphocytes, cells that are essential in the immune defense because they are able to recognize cells already infected by the parasite and eliminate them before the infection spreads further.
The researchers observed that several identified peptides are presented through different variants of HLA class I molecules, including HLA-A, HLA-B, HLA-C, and even the non-classical molecule HLA-E. This suggests that the same antigens may be recognized by individuals with different genetic characteristics, increasing the potential use of future vaccines in very diverse populations.
Results confirmed in several experimental models
The validation of the identified antigens was carried out using samples from people infected by both plasmodium vivax be from Plasmodium falciparum.
In parallel, the research has highlighted specific immune responses also in experimental models with other species of Plasmodium. In nonhuman primates, for example, several antigens stimulated T lymphocytes in both the blood and liver after infection or immunization with attenuated parasites.
The most promising results also came from studies conducted in rodents, where two of the identified antigens were shown to induce an immune response mediated by CD8+ T lymphocytes capable of reducing the parasite load, thus showing a protective effect.
Two species of malaria at the center of the study
The research mainly examines the two main species responsible for malaria in humans.
Plasmodium falciparum It represents the most widespread form on the African continent and is associated with the most severe cases of the disease. plasmodium vivax, however, is predominant in the Americas and much of Asia and has different biological characteristics, including the ability to infect exclusively reticulocytes, immature red blood cells that retain RNA and maintain limited protein synthesis activity.
Previous studies by the same group had demonstrated that these infected reticulocytes express HLA class I molecules, making it possible for CD8+ T lymphocytes to recognize the infected cells.
The prospects for future vaccines
Although further studies are needed before clinical application, the research published in Nature It offers a new platform for designing malaria vaccines based on antigens shared between different species of the parasite and active at different stages of its biological cycle.
The identification of highly conserved targets could contribute to the development of more universal vaccination strategies compared to current ones, with the aim of increasing the duration of protection and improving efficacy against the different forms of the disease.
The work of the IRB in Bellinzona thus represents a significant contribution to international research on malaria, making available to the scientific community a catalog of antigens that can be used as a starting point for next generations of vaccines.
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