Functional Analysis Reveals Geographical Variation in Inhibitory Immune Responses Against a Polymorphic Malaria Antigen
Year: 2017
Type: article
Abstract: Background: Plasmodium falciparum reticulocyte-binding protein homologue 2b (PfRh2b) is an invasion ligand that is a potential blood-stage vaccine candidate antigen; however, a naturally occurring deletion within an immunogenic domain is present at high frequencies in Africa and has been associated with alternative invasion pathway usage. Standardized tools that provide antigenic specificity in in vitro assays are needed to functionally assess the neutralizing potential of humoral responses against malaria vaccine candidate antigens. Methods: Transgenic parasite lines were generated to express the PfRh2b deletion. Total immunoglobulin G (IgG) from individuals residing in malaria-endemic regions in Tanzania, Senegal, and Mali were used in growth inhibition assays with transgenic parasite lines. Results: While the PfRh2b deletion transgenic line showed no change in invasion pathway utilization compared to the wild-type in the absence of specific antibodies, it outgrew wild-type controls in competitive growth experiments. Inhibition differences with total IgG were observed in the different endemic sites, ranging from allele-specific inhibition to allele-independent inhibitory immune responses. Conclusions: The PfRh2b deletion may allow the parasite to escape neutralizing antibody responses in some regions. This difference in geographical inhibition was revealed using transgenic methodologies, which provide valuable tools for functionally assessing neutralizing antibodies against vaccine-candidate antigens in regions with varying malaria endemicity.
Institutions: Harvard University, Hôpital Aristide Le Dantec, Cheikh Anta Diop University, Boston Children's Hospital, National Institutes of Health, National Institute of Allergy and Infectious Diseases, Muhimbili University of Health and Allied Sciences, Aga Khan University Hospital Nairobi, Aga Khan University Nairobi, Université des Sciences, des Techniques et des Technologies de Bamako, Malaria Research and Training Center, Institute of Health Research, Epidemiological Surveillance and Training
Language: English
Topic: Malaria Research and Control
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Funders: U.S. Department of State, National Institutes of Health, Centers for Disease Control and Prevention, National Institute of Allergy and Infectious Diseases, Fogarty International Center, National Institute of Child Health and Human Development, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: G1574827469, Employing Genetic and Genomic Surveillance to Reveal Mechanisms of Malaria Parasite Persistance, G1730213550, Molecular characterization and substrate identification of malaria kinase PfCDPK5, G2051510764, G355924648, G3741238477, Molecular analysis of a kinase essential for replication of Plasmodium falciparum, Erythrocyte invasion by Plasmodium falciparum merozoites, G4202505388, G518948582, G5288657676, G7000853137, Molecular analysis of erythrocyte invasion in malaria isolates from Senegal, G8580348208, Intellectual and Developmental Disablities Research Center, Epidemiology of Infectious Diseases, Pediatric Scientist Development Program
OpenAlex ID: W2624476313