Next-Generation Vaccines Against Neglected Diseases: New Promises from Genetically Modified Live-Attenuated Parasites and RNA Vaccines.

Different protozoan parasites are the causative agents of tropical diseases, including malaria, toxoplasmosis, leishmaniasis, and Chagas disease (CD), which, altogether, affect over 300 million people throughout the world. Except for two recently approved malaria vaccines, individuals affected by or at risk of contracting any of these four diseases still experience a lack of effective treatments and vaccines. Many vaccine studies, including those that have reached clinical trials, are based on inactivated parasites, adjuvanted recombinant proteins, or viral vector vaccines. Here, we review the current advances towards the development of vaccines based on genetically modified live-attenuated parasites (GMLAP) as well as RNA formulations encoding parasite antigens. Because these are diseases caused by intracellular pathogens that depend on efficient T-cell responses for parasite control, these two new vaccine platforms have generated great expectations, since they are known to induce a robust cellular immune response. Although preclinical studies aimed at developing new malaria, toxoplasmosis, and leishmaniasis vaccines have led to significant progress that may soon result in clinical trials, advances in next-generation vaccines against CD are lagging behind. Increased collaborative efforts between research groups, governments, and the pharmaceutical industry, particularly in Africa, Asia, and Latin American countries, are urgently needed to accelerate the development of vaccines for all neglected and less-studied diseases.