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Comparative analyses of functional antibody-mediated inhibition with anti-circumsporozoite monoclonal antibodies against transgenic Plasmodium berghei.

Authors
  • Nicholas, Justin1, 2
  • Kolli, Surendra Kumar1
  • Subramani, Pradeep Annamalai1
  • De, Sai Lata1, 3
  • Ogbondah, Madison M1
  • Barnes, Samantha J1
  • Ntumngia, Francis Babila1
  • Adams, John H4
  • 1 Center for Global Health and Interdisciplinary Research, College of Public Health, University of South Florida, 3720 Spectrum Blvd, Tampa, FL, 33612, USA.
  • 2 Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL, 33612, USA.
  • 3 Department of Infectious Disease & Immunology, College of Veterinary Medicine, University of Florida, Gainesville, FL, 32611, USA.
  • 4 Center for Global Health and Interdisciplinary Research, College of Public Health, University of South Florida, 3720 Spectrum Blvd, Tampa, FL, 33612, USA. [email protected].
Type
Published Article
Journal
Malaria Journal
Publisher
Springer (Biomed Central Ltd.)
Publication Date
Nov 07, 2023
Volume
22
Issue
1
Pages
335–335
Identifiers
DOI: 10.1186/s12936-023-04765-2
PMID: 37936181
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Acquired functional inhibitory antibodies are one of several humoral immune mechanisms used to neutralize foreign pathogens. In vitro bioassays are useful tools for quantifying antibody-mediated inhibition and evaluating anti-parasite immune antibodies. However, a gap remains in understanding of how antibody-mediated inhibition in vitro translates to inhibition in vivo. In this study, two well-characterized transgenic Plasmodium berghei parasite lines, PbmCh-luc and Pb-PfCSP(r), and murine monoclonal antibodies (mAbs) specific to P. berghei and Plasmodium falciparum circumsporozoite protein (CSP), 3D11 and 2A10, respectively, were used to evaluate antibody-mediated inhibition of parasite development in both in vitro and in vivo functional assays. IC50 values of mAbs were determined using an established inhibition of liver-stage development assay (ILSDA). For the in vivo inhibition assay, mice were passively immunized by transfer of the mAbs and subsequently challenged with 5.0 × 103 sporozoites via tail vein injection. The infection burden in both assays was quantified by luminescence and qRT-PCR of P. berghei 18S rRNA normalized to host GAPDH. The IC50 values quantified by relative luminescence of mAbs 3D11 and 2A10 were 0.396 µg/ml and 0.093 µg/ml, respectively, against transgenic lines in vitro. Using the highest (> 90%) inhibitory antibody concentrations in a passive transfer, an IC50 of 233.8 µg/ml and 181.5 µg/ml for mAbs 3D11 and 2A10, respectively, was observed in vivo. At 25 µg (250 µg/ml), the 2A10 antibody significantly inhibited liver burden in mice compared to control. Additionally, qRT-PCR of P. berghei 18S rRNA served as a secondary validation of liver burden quantification. Results from both experimental models, ILSDA and in vivo challenge, demonstrated that increased concentrations of the homologous anti-CSP repeat mAbs increased parasite inhibition. However, differences in antibody IC50 values between parasite lines did not allow a direct correlation between the inhibition of sporozoite invasion in vitro by ILSDA and the inhibition of mouse liver stage burden. Further studies are needed to establish the conditions for confident predictions for the in vitro ILSDA to be a predictor of in vivo outcomes using this model system. © 2023. The Author(s).

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