Proceso para el desarrollo de una vacuna contra la fase hepática de Plasmodium vivax

Introducción: Anualmente se producen en el mundo entre 80 y 100 millones de casos de malaria ocasionada por Plasmodium vivax, segunda especie de Plasmodium en importancia a nivel mundial y primera en el continente americano. Ante la falla de los métodos clásicos de control de la malaria, derivada de la creciente resistencia de los mosquitos a los insecticidas y de los parásitos a los medicamentos disponibles, se ha trabajado intensamente en la búsqueda de vacunas que puedan prevenir completamente la infección o limitar los efectos patológicos de la enfermedad. Objetivos: Este trabajo describe el proceso de desarrollo de una vacuna experimental dirigida contra las formas pre-eritrocíticas del parásito, para lo cual se ha seleccionado la proteína circumesporozoito (CS) que se expresa de forma abundante en la superficie del parásito y que se halla comprometida en el proceso de invasión hepática. Metodología: El proceso consistió en una exhaustiva caracterización inmunológica de la proteína, mediante péptidos sintéticos de diferente longitud, seguida de pruebas de toxicidad e inmunogenicidad en animales con los tres péptidos largos que cubren las regiones N, R y C de la CS. Como etapa inicial de la prueba en humanos, se hizo un ensayo clínico fase I que probó la seguridad e inmunogenicidad, de cada uno de los péptidos formulados en el adyuvante Montanide ISA-720. El ensayo fue al azar, doble ciego y comprometió a 23 voluntarios sanos, hombres y mujeres entre 18 y 33 años de edad, sin historia de malaria. Conclusiones: La vacuna fue muy bien tolerada y demostró buena seguridad e inmunogenicidad en los ensayos preclínicos así como en todos los voluntarios, facilitando el avance a ulteriores fases de investigación clínica. Introduction: Plasmodium vivax causes approximately 80-100 million clinical cases every year. It is the most prevalent human malaria parasite in the American continent and its prevalence is second only to P. falciparum worldwide. Due to the emergence of medication-resistant parasites and an increase in insecticide-resistant mosquitoes, research to find a vaccine that could prevent or limit the clinical manifestations of the disease has increased greatly. During the last two decades, significant progress has been achieved in this attempt; however, the development of a P. vivax vaccine has been hampered due to the lack of sustainable in vitro parasite cultures. Objectives: We describe the development and testing of a vaccine to P. vivax pre-erythrocytic stages. We selected the circumsporozoite (CS) protein, an antigen abundantly expressed on the parasite surface. Methodology: After extensive immunological characterization in vitro, three long peptides (N, R and C) were synthesized, and the toxicity and immunogenicity of these peptides were thoroughly assessed in animals. To determine the safety and immunogenicity in humans, a randomized, double blind clinical trial was conducted. The trial included 23 healthy volunteers who received 100 μg of N, R and C of each peptide formulated in Montanide ISA-720 adjuvant. Conclusions: The vaccination was well tolerated and proven to be safe in both animals and volunteers; thus, additional clinical trials utilizing this vaccine candidate are indicated

Proceso para el desarrollo de una vacuna contra la fase hepática de Plasmodium vivax

Introduction: Plasmodium vivax   causes approximately 80-100 million clinical cases every year. It is the most prevalent human malaria parasite in the American continent and its prevalence is second only to P. falciparum worldwide. Due to the emergence of medication-resistant parasites and an increase in insecticide-resistant mosquitoes, research to find a vaccine that could prevent or limit the clinical manifestations of the disease has increased greatly. During the last two decades, significant progress has been achieved in this attempt; however, the development of a P. vivax vaccine has been hampered due to the lack of sustainable in vitro parasite cultures. Objectives: We describe the development and testing of a vaccine to P. vivax pre-erythrocytic stages. We selected the circumsporozoite (CS) protein, an antigen abundantly expressed on the parasite surface. Methodology: After extensive immunological characterization in vitro, three long peptides (N, R and C) were synthesized, and the toxicity and immunogenicity of these peptides were thoroughly assessed in animals. To determine the safety and immunogenicity in humans, a randomized, double blind clinical trial was conducted. The trial included 23 healthy volunteers who received 100 μg of N, R and C of each peptide formulated in Montanide ISA-720 adjuvant. Conclusions: The vaccination was well tolerated and proven to be safe in both animals and volunteers; thus, additional clinical trials utilizing this vaccine candidate are indicated