RESUMEN
The Duffy binding protein of Plasmodium vivax (DBP) is a critical adhesion ligand that participates in merozoite invasion of human Duffy-positive erythrocytes. A small outbreak of P. vivax malaria, in a village located in a non-malarious area of Brazil, offered us an opportunity to investigate the DBP immune responses among individuals who had their first and brief exposure to malaria. Thirty-three individuals participated in the five cross-sectional surveys, 15 with confirmed P. vivax infection while residing in the outbreak area (cases) and 18 who had not experienced malaria (non-cases). In the present study, we found that only 20% (three of 15) of the individuals who experienced their first P. vivax infection developed an antibody response to DBP; a secondary boosting can be achieved with a recurrent P. vivax infection. DNA sequences from primary/recurrent P. vivax samples identified a single dbp allele among the samples from the outbreak area. To investigate inhibitory antibodies to the ligand domain of the DBP (cysteine-rich region II, DBP(II)), we performed in vitro assays with mammalian cells expressing DBP(II) sequences which were homologous or not to those from the outbreak isolate. In non-immune individuals, the results of a 12-month follow-up period provided evidence that naturally acquired inhibitory antibodies to DBP(II) are short-lived and biased towards a specific allele.
Asunto(s)
Anticuerpos Antiprotozoarios/sangre , Antígenos de Protozoos/inmunología , Malaria Vivax/inmunología , Plasmodium vivax/inmunología , Proteínas Protozoarias/inmunología , Receptores de Superficie Celular/inmunología , Adulto , Alelos , Animales , Antígenos de Protozoos/genética , Brasil/epidemiología , Estudios Transversales , ADN Protozoario/genética , Brotes de Enfermedades , Humanos , Malaria Vivax/epidemiología , Malaria Vivax/parasitología , Proteína 1 de Superficie de Merozoito/inmunología , Persona de Mediana Edad , Plasmodium vivax/genética , Proteínas Protozoarias/genética , Receptores de Superficie Celular/genética , Adulto JovenRESUMEN
The function of the Plasmodium vivax Duffy binding protein (DBP) during the erythrocyte invasion process is critical for successful parasite growth and pathogenesis in human infections. Although DBP is the subject of intensive malaria vaccine research, investigations on the functional proprieties of anti-DBP antibodies in the human population have been limited [Infect Immun68 (2000) 3164]. In the present study, we examined the ability of sera from different populations of the Brazilian Amazon--an area of markedly unstable malaria transmission--to inhibit the erythrocyte-binding function of the DBP ligand domain (region II, DBP(II)). We found that long-term exposure to malaria in the Amazon area elicits DBP-specific antibodies that inhibit the binding of different DBP(II) variants to erythrocytes. Despite the great variability of inhibitory antibody responses observed among study participants, we observed a positive correlation between erythrocyte binding-inhibitory activity and enzyme-linked immunosorbent assay anti-DBP antibodies. Of importance, there was a non-significant tendency towards increased levels of anti-DBP antibodies among individuals with asymptomatic P. vivax infections.
Asunto(s)
Anticuerpos Antiprotozoarios/sangre , Antígenos de Protozoos/inmunología , Malaria Vivax/sangre , Malaria Vivax/inmunología , Proteínas Protozoarias/inmunología , Receptores de Superficie Celular/inmunología , Animales , Antígenos de Protozoos/genética , Brasil , Ensayo de Inmunoadsorción Enzimática , Eritrocitos/inmunología , Eritrocitos/metabolismo , Humanos , Malaria Vivax/transmisión , Microscopía Confocal , Plasmodium vivax/inmunología , Polimorfismo Genético , Proteínas Protozoarias/genética , Receptores de Superficie Celular/genética , TransfecciónRESUMEN
The Plasmodium vivax Duffy binding protein (DBP) is essential during merozoite invasion into human erythrocytes. Because of its biological importance, the DBP is also seen to have potential use as a malaria blood-stage vaccine. We have used a soluble recombinant DBP (rDBP) containing the functional ligand domain to assess the natural immunogenicity of DBP in a low-endemic vivax malaria region. Human sera from adult residents from a Colombian village with unstable vivax malaria transmission reacted specifically with the rDBP as determined by ELISA. There was a significant positive correlation between increased antibody response (average, median, and percent positives) and age of patients, although the level of responses did vary considerably in their reactivity to the rDBP from negative to very high level within each age group. These data confirm previous findings on the serologic reactivity of the DBP in exposed populations and that immunologic boosting to the DBP occurs in malaria-endemic regions even with low-level transmission.