RESUMEN
BACKGROUND: The Plasmodium falciparum P126 protein is an asexual blood-stage malaria vaccine candidate antigen. Antibodies against P126 are able to inhibit parasite growth in vitro, and a major parasite-inhibitory epitope has been recently mapped to its 47 kDa N-terminal extremity (octamer repeat domain--OR domain). The OR domain basically consists of six octamer units, but variation in the sequence and number of repeat units may appear in different alleles. The aim of the present study was to investigate the polymorphism of P126 N-terminal region OR domain in P. falciparum isolates from two Brazilian malaria endemic areas and its impact on anti-OR naturally acquired antibodies. METHODS: The study was carried out in two villages, Candeias do Jamari (Rondonia state) and Peixoto de Azevedo (Mato Grosso state), both located in the south-western part of the Amazon region. The repetitive region of the gene encoding the P126 antigen was PCR amplified and sequenced with the di-deoxy chain termination procedure. The antibody response was evaluated by ELISA with the Nt47 synthetic peptide corresponding to the P126 OR-II domain. RESULTS: Only two types of OR fragments were identified in the studied areas, one of 175 bp (OR-I) and other of 199 bp (OR-II). A predominance of the OR-II fragment was observed in Candeias do Jamari whereas in Peixoto de Azevedo both fragments OR-I and OR-II were frequent as well as mixed infection (both fragments simultaneously) reported here for the first time. Comparing the DNA sequencing of OR-I and OR-II fragments, there was a high conservation among predicted amino acid sequences of the P126 N-terminal extremity. Data of immune response demonstrated that the OR domain is highly immunogenic in natural conditions of exposure and that the polymorphism of the OR domain does not apparently influence the specific immune response. CONCLUSION: These findings confirm a limited genetic polymorphism of the P126 OR domain in P. falciparum isolates and that this limited genetic polymorphism does not seem to influence the development of a specific humoral immune response to P126 and its immunogenicity in the studied population.
Asunto(s)
Anticuerpos Antiprotozoarios/inmunología , Polimorfismo Genético , Proteínas Protozoarias/genética , Proteínas Protozoarias/inmunología , Animales , Brasil , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Masculino , Reacción en Cadena de la Polimerasa , Polimorfismo Conformacional Retorcido-Simple , Análisis de Secuencia de ADNRESUMEN
The antibody response to Plasmodium falciparum parasites of naturally infected population is critical to elucidate the role of polymorphic alleles in malaria. Thus, we evaluated the impact of antigenic diversity of repetitive and family dimorphic domains of the merozoite surface protein 2 (MSP-2) on immune response of 96 individuals living in Peixoto de Azevedo (MT-Brazil), by ELISA using recombinant MSP-2 proteins. The majority of these individuals were carrying FC27-type infections. IgG antibody responses were predominantly directed to FC27 parasites and were correlated to the extension of polymorphism presented by each MSP-2 region. This finding demonstrated the impact of the genetic polymorphism on antibody response and therefore, its importance on malaria vaccine efficacy.
Asunto(s)
Anticuerpos Antiprotozoarios/inmunología , Especificidad de Anticuerpos , Antígenos de Protozoos/genética , Malaria Falciparum/parasitología , Plasmodium falciparum/genética , Plasmodium falciparum/inmunología , Proteínas Protozoarias/genética , Enfermedad Aguda , Adulto , Alelos , Animales , Anticuerpos Antiprotozoarios/sangre , Antígenos de Protozoos/inmunología , Brasil/epidemiología , Enfermedades Endémicas , Ensayo de Inmunoadsorción Enzimática , Humanos , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Malaria Falciparum/epidemiología , Malaria Falciparum/inmunología , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Polimorfismo Genético , Polimorfismo Conformacional Retorcido-Simple , Proteínas Protozoarias/inmunologíaRESUMEN
The antibody response to Plasmodium falciparum parasites of naturally infected population is critical to elucidate the role of polymorphic alleles in malaria. Thus, we evaluated the impact of antigenic diversity of repetitive and family dimorphic domains of the merozoite surface protein 2 (MSP-2) on immune response of 96 individuals living in Peixoto de Azevedo (MT-Brazil), by ELISA using recombinant MSP-2 proteins. The majority of these individuals were carrying FC27-type infections. IgG antibody responses were predominantly directed to FC27 parasites and were correlated to the extension of polymorphism presented by each MSP-2 region. This finding demonstrated the impact of the genetic polymorphism on antibody response and therefore, its importance on malaria vaccine efficacy.