Breadth of functional antibodies is associated with Plasmodium falciparum merozoite phagocytosis and protection against febrile malaria

TY - JOUR

T1 - Breadth of functional antibodies is associated with Plasmodium falciparum merozoite phagocytosis and protection against febrile malaria

AU - Kana, Ikhlaq Hussain

AU - Singh, Susheel Kumar

AU - Garcia-Senosiain, Asier

AU - Dodoo, Daniel

AU - Singh, Subhash

AU - Adu, Bright

AU - Theisen, Michael

N1 - © The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: [email protected].

PY - 2019/6/19

Y1 - 2019/6/19

N2 - BACKGROUND: The specific targets of functional antibodies against Plasmodium falciparum merozoites remain largely unexplored and, more importantly, their relevance to naturally acquired immunity in longitudinal cohort studies (LCSs) is yet to be tested.METHODS: Functionality of immunoglobulin G (IgG) antibodies against 24 merozoite antigens was determined at the baseline of an LCS in Ghana using a bead-based opsonic phagocytosis assay (BPA). Antigen-specific IgG3 subclass antibodies were quantified in the same samples by the Luminex multiplex system.RESULTS: A wide range of BPA activity was observed across the different antigens. High BPA responses of nMSP3K1, GLURP-R2, MSP23D7, MSP119k, and PfRh2-2030 coupled beads were significantly associated with a higher probability of children not experiencing febrile malaria. Children with high breadth of functional antibodies against these antigens together with cMSP33D7 had a significantly reduced risk of febrile malaria (adjusted hazard ratio, 0.36 [95% confidence interval, .18-.72]; P = .004). Five of the 6 BPA activities significantly (likelihood ratio rest, P ≤ .05) contributed to the protective immunity observed with the IgG3 antibodies.CONCLUSIONS: The development of BPA allowed profiling of functional antibodies in an LCS. Identification of targets of opsonic phagocytosis may have implications in the development of a subunit malaria vaccine.

AB - BACKGROUND: The specific targets of functional antibodies against Plasmodium falciparum merozoites remain largely unexplored and, more importantly, their relevance to naturally acquired immunity in longitudinal cohort studies (LCSs) is yet to be tested.METHODS: Functionality of immunoglobulin G (IgG) antibodies against 24 merozoite antigens was determined at the baseline of an LCS in Ghana using a bead-based opsonic phagocytosis assay (BPA). Antigen-specific IgG3 subclass antibodies were quantified in the same samples by the Luminex multiplex system.RESULTS: A wide range of BPA activity was observed across the different antigens. High BPA responses of nMSP3K1, GLURP-R2, MSP23D7, MSP119k, and PfRh2-2030 coupled beads were significantly associated with a higher probability of children not experiencing febrile malaria. Children with high breadth of functional antibodies against these antigens together with cMSP33D7 had a significantly reduced risk of febrile malaria (adjusted hazard ratio, 0.36 [95% confidence interval, .18-.72]; P = .004). Five of the 6 BPA activities significantly (likelihood ratio rest, P ≤ .05) contributed to the protective immunity observed with the IgG3 antibodies.CONCLUSIONS: The development of BPA allowed profiling of functional antibodies in an LCS. Identification of targets of opsonic phagocytosis may have implications in the development of a subunit malaria vaccine.

U2 - 10.1093/infdis/jiz088

DO - 10.1093/infdis/jiz088

M3 - Journal article

C2 - 30820557

SN - 0022-1899

VL - 220

SP - 275

EP - 284

JO - The Journal of Infectious Diseases

JF - The Journal of Infectious Diseases

IS - 2

ER -