Live attenuated vaccines, a favorable strategy to provide long-term immunity against protozoan diseases

• Published in: Trends in parasitology 2022-04, Vol.38 (4), p.316-334
• Main Authors: Solana, Jose C., Moreno, Javier, Iborra, Salvador, Soto, Manuel, Requena, Jose M.
• Format: Article
• Language: English
• Subjects: Animals; Antigens, Protozoan; attenuated vaccines; Chagas disease; genetically modified parasites; leishmaniasis; Leishmaniasis - prevention & control; malaria; Malaria - prevention & control; Malaria Vaccines; Protozoan Vaccines; Sporozoites; Vaccines, Attenuated
• ISSN: 1471-4922; 1471-5007
• DOI: 10.1016/j.pt.2021.11.004

The control of diseases caused by protozoan parasites is one of the United Nations' Sustainable Development Goals. In recent years much research effort has gone into developing a new generation of live attenuated vaccines (LAVs) against malaria, Chagas disease and leishmaniasis. However, there is a bottleneck related to their biosafety, production, and distribution that slows downs further development. The success of irradiated or genetically attenuated sporozoites against malaria, added to the first LAV against leishmaniasis to be evaluated in clinical trials, is indicative that the drawbacks of LAVs are gradually being overcome. However, whether persistence of LAVs is a prerequisite for sustained long-term immunity remains to be clarified, and the procedures necessary for clinical evaluation of vaccine candidates need to be standardized. Malaria, Chagas' disease, and leishmaniasis are the parasitic diseases causing the highest morbidity/mortality rates and have a worldwide distribution. Efforts to develop effective vaccines are urgent.The insufficient efficacy of subunit vaccines has led to renewed interest in vaccination strategies based on live parasites.Natural immunization after infection is more the norm than the exception, as shown by the higher percentage of asymptomatic individuals observed in endemic areas.The persistence of the parasite allows an effective immune response in the long term (concomitant immunity). This involves important biosafety issues that must be evaluated.The current genetic manipulation tools have allowed the creation of promising live attenuated vaccines, which, together with advances in manufacturing and distribution of live organisms, suggest that clinical evaluation is timely.