Genome-Level Determination of Plasmodium falciparum Blood-Stage Targets of Malarial Clinical Immunity in the Peruvian Amazon

Autor: Mayuko Saito, Huw Davies, Joseph M. Vinetz, Philip L. Felgner, Eli L. Moss, Carlos Castrillon, Dionicia Gamboa, Daniel E. Neafsey, Katherine Torres, Douglas M. Molina, Roy Tenorio
Rok vydání: 2014
Předmět:
Adult
Male
Adolescent
Plasmodium falciparum
Protozoan Proteins
malaria
Antibodies
Protozoan
Antigens
Protozoan
Parasitemia
purl.org/pe-repo/ocde/ford#3.03.08 [https]
Asymptomatic
immunology
Plasmodium falciparum/genetics/immunology
Major Articles and Brief Reports
Young Adult
Immune system
Immunity
Malaria Vaccines
parasitic diseases
medicine
Humans
Malaria
Falciparum/blood/immunology
Parasitemia/blood/immunology/parasitology
Immunology and Allergy
Malaria
Falciparum
Child
Malaria Vaccines/immunology
biology
Malaria vaccine
Antibodies
Protozoan/immunology
Antigens
Protozoan/genetics/immunology
systems biology
Protozoan Proteins/blood/genetics/immunology
Middle Aged
biology.organism_classification
Acquired immune system
medicine.disease
Virology
Infectious Diseases
Immunology
Female
geographic medicine
medicine.symptom
Malaria
Zdroj: The Journal of Infectious Diseases. 211:1342-1351
ISSN: 1537-6613
0022-1899
DOI: 10.1093/infdis/jiu614
Popis: Dogma in the malaria field holds that acquisition of clinical immunity to Plasmodium falciparum malaria results from the interaction of 2 factors. Specifically, the production of antigen-specific antibody [1, 2] and repeated parasite exposures over many transmission seasons are required for the onset of clinically protective immune responses as manifested by asymptomatic parasitemia [2], also called premonition [3]. These patterns have been characteristic of regions with high malaria transmission, primarily in sub-Saharan Africa [2, 4]. An exception to this was reported among previously malaria-naive adult transmigrants to Irian Jaya in the 1980s, who developed clinical immunity to P. falciparum within 2 years of arrival to this region of high malaria endemicity [5]. Previous studies using systems immunology/protein microarray experiments inferred antigen-specific immune responses by analyzing sera from residents of P. falciparum–endemic regions of Mali [4]. These data have been interpreted to indicate the concept that the development of acquired immunity is dependent on age and exposure to multiple infections, insofar as age can be considered a surrogate of clinical immunity and in areas where malaria infections are common and intense during annual rainy seasons [4]. Nonetheless, asymptomatic malarial parasite infections are common in Brazilian and Peruvian Amazonia, where transmission is considered to be hypoendemic and of low intensity [6–11]. Importantly, these well-established observations of asymptomatic parasitemia in Amazonia imply that clinical immunity may develop more rapidly in low-transmission settings [6–8, 12–15], which stands in contrast to high-transmission regions, where acquired immunity is manifested by asymptomatic parasitemia that takes years and intense seasonal or continuous transmission to develop [1, 4, 16, 17]. These observations imply that the immunological mechanisms underlying the acquisition of clinical immunity in areas with high as opposed to low transmission must be different and remain an unexplored yet high-priority area of the malaria field. In the Amazon region, asymptomatic malaria parasitemia is common, and cases are not detected by passive case detection under normal surveillance, which conventionally relies on symptoms to drive diagnostic testing [8, 9]. Furthermore, clinically immune individuals are likely to be reservoirs of ongoing malaria transmission, and, perhaps just as important, understanding these acquired immune mechanisms may lead toward the development of new malaria vaccine strategies. In this context, there is evidence that antibody-dependent mechanisms play an important role in the reduction of parasitemia and can diminish clinical symptoms in humans, as was demonstrated by the passive transfer of hyperimmune immunoglobulin G (IgG) [1]. For this study, we used genome-scale protein microarrays to analyze the IgG responses to >800 recombinant proteins of asexual blood-stage P. falciparum in P. falciparum–infected subjects in the Peruvian Amazon. We hypothesized that asymptomatic subjects with P. falciparum parasitemia would differentially recognize a subset of P. falciparum proteins, compared with symptomatic patients, implying a contribution of these proteins to protective immune responses. Our objective was to compare antibody responses in symptomatic and asymptomatic individuals. We determined whether differentially recognized proteins in these 2 groups of malaria-affected subjects had undergone immune selection at a genomic level, to seek independent confirmation for a potential role in naturally acquired clinical immunity. Finally, we sought to identify the most immunodominant antigens shared by symptomatic and asymptomatic subjects, on a genomic scale, to identify novel candidate antigens for seroepidemiological surveillance.
Databáze: OpenAIRE
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