@article{Ogwang:2024:10.3389/fimmu.2024.1360220,
author = {Ogwang, R and Murugu, L and Nailain, I and Nyamako, L and Kai, O and Mwai, K and Murungi, L and Idro, R and Bejon, P and Tuju, J and Kinyanjui, SM and Osier, FHA},
doi = {10.3389/fimmu.2024.1360220},
journal = {Frontiers in Immunology},
title = {Bi-isotype immunoglobulins enhance antibody-mediated neutrophil activity against Plasmodium falciparum parasites},
url = {http://dx.doi.org/10.3389/fimmu.2024.1360220},
volume = {15},
year = {2024}
}

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TY  - JOUR
AB  - Background: Malaria remains a major global health priority, and monoclonal antibodies (mAbs) are emerging as potential new tools to support efforts to control the disease. Recent data suggest that Fc-dependent mechanisms of immunity are important mediators of protection against the blood stages of the infection, but few studies have investigated this in the context of mAbs. We aimed to isolate mAbs agnostic to cognate antigens that target whole merozoites and simultaneously induce potent neutrophil activity measured by the level of reactive oxygen species (ROS) production using an antibody-dependent respiratory burst (ADRB) assay.Methods: We used samples from semi-immune adults living in coastal Kenya to isolate mAbs that induce merozoite-specific ADRB activity. We then tested whether modifying the expressed IgG1 isotype to an IgG–IgA Fc region chimera would enhance the level of ADRB activity.Results: We isolated a panel of nine mAbs with specificity to whole merozoites. mAb J31 induced ADRB activity in a dose-dependent fashion. Compared to IgG1, our modified antibody IgG–IgA bi-isotype induced higher ADRB activity across all concentrations tested. Further, we observed a negative hook effect at high IgG1 mAb concentrations (i.e., >200 µg/mL), but this was reversed by Fc modification. We identified MSP3.5 as the potential cognate target of mAb J31.Conclusions: We demonstrate an approach to engineer mAbs with enhanced ADRB potency against blood-stage parasites.
AU  - Ogwang,R
AU  - Murugu,L
AU  - Nailain,I
AU  - Nyamako,L
AU  - Kai,O
AU  - Mwai,K
AU  - Murungi,L
AU  - Idro,R
AU  - Bejon,P
AU  - Tuju,J
AU  - Kinyanjui,SM
AU  - Osier,FHA
DO  - 10.3389/fimmu.2024.1360220
PY  - 2024///
SN  - 1664-3224
TI  - Bi-isotype immunoglobulins enhance antibody-mediated neutrophil activity against Plasmodium falciparum parasites
T2  - Frontiers in Immunology
UR  - http://dx.doi.org/10.3389/fimmu.2024.1360220
UR  - https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1360220/full
UR  - http://hdl.handle.net/10044/1/111101
VL  - 15
ER  - 

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