New developments in malaria diagnostics: monoclonal antibodies against Plasmodium dihydrofolate reductase-thymidylate synthase, heme detoxification protein and glutamate rich protein

Johanna H Kattenberg, Inge Versteeg, Stephanie J Migchelsen, Iveth J González, Mark D Perkins, Petra F Mens, Henk D F H Schallig

Research output: Contribution to journalA1: Web of Science-article

Abstract

Currently available rapid diagnostic tests (RDTs) for malaria show large variation in sensitivity and specificity, and there are concerns about their stability under field conditions. To improve current RDTs, monoclonal antibodies (mAbs) for novel malaria antigens have been developed and screened for their possible use in new diagnostic tests. Three antigens, glutamate rich protein (GLURP), dihydrofolate reductase-thymidylate synthase (DHFR-TS) and heme detoxification protein (HDP), were selected based on literature searches. Recombinant antigens were produced and used to immunize mice. Antibody-producing cell lines were subsequently selected and the resulting antibodies were screened for specificity against Plasmodium falciparum and Plasmodium vivax. The most optimal antibody couples were selected based on antibody affinity (expressed as dissociation constants, KD) and detection limit of crude antigen extract from P. falciparum 3D7 culture. The highest affinity antibodies have KD values of 0.10 nM ± 0.014 (D5) and 0.068 ± 0.015 nM (D6) for DHFR-TS mAbs, 0.10 ± 0.022 nM (H16) and 0.21 ± 0.022 nM (H18) for HDP mAbs and 0.11 ± 0.028 nM (G23) and 0.33 ± 0.093 nM (G22) for GLURP mAbs. The newly developed antibodies performed at least as well as commercially available histidine rich protein antibodies (KD of 0.16 ± 0.13 nM for PTL3 and 1.0 ± 0.049 nM for C1-13), making them promising reagents for further test development.

Original languageEnglish
JournalMAbs
Volume4
Issue number1
Pages (from-to)120-126
Number of pages7
ISSN1942-0862
DOIs
Publication statusPublished - 2012
Externally publishedYes

Keywords

  • Animals
  • Antibodies, Monoclonal
  • Antibodies, Protozoan
  • Antigens, Protozoan
  • Humans
  • Immunization
  • Malaria, Falciparum
  • Malaria, Vivax
  • Mice
  • Mice, Inbred BALB C
  • Multienzyme Complexes
  • Plasmodium falciparum
  • Plasmodium vivax
  • Protozoan Proteins
  • Recombinant Proteins
  • Tetrahydrofolate Dehydrogenase
  • Thymidylate Synthase
  • Journal Article
  • Research Support, Non-U.S. Gov't

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