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Antibody Feedback Limits the Expansion of B Cell Responses to Malaria Vaccination but Drives Diversification of the Humoral Response

October 15, 2020 - 08:50 -- Open Access
McNamara HA, Idris AH, Cockburn IA, et al.
Cell Host Microbe. 2020 Oct 7;28(4):572-585.e7

Generating sufficient antibody to block infection is a key challenge for vaccines against malaria. Here, we show that antibody titers to a key target, the repeat region of the Plasmodium falciparum circumsporozoite protein (PfCSP), plateaued after two immunizations in a clinical trial of the radiation-attenuated sporozoite vaccine. To understand the mechanisms limiting vaccine responsiveness, we developed immunoglobulin (Ig)-knockin mice with elevated numbers of PfCSP-binding B cells.

ITEM-THREE analysis of a monoclonal anti-malaria antibody reveals its assembled epitope on the pfMSP119 antigen

September 1, 2020 - 10:05 -- Open Access
Opuni KFM, Koy C, Russ M, Reepmeyer M, Danquah BD, Weresow M, Alef A, Lorenz P, Thiesen HJ, Glocker MO
J Biol Chem. 2020 Aug 26:jbc.RA120.014802

Rapid diagnostic tests are first line assays for diagnosing infectious diseases, such as malaria. To minimize false positive and false negative test results in population screening assays, high quality reagents and well characterized antigens and antibodies are needed. An important property of antigen - antibody binding is recognition specificity which best can be estimated by mapping an antibody's epitope on the respective antigen.

Evaluation of antibody responses to the early transcribed membrane protein family in Plasmodium vivax

January 15, 2020 - 09:24 -- Open Access
Lee SK, Han JH, Park JH, Ha KS, Park WS, Hong SH, Na S, Cheng Y, Han ET
Parasites & Vectors volume, 2019 Dec 19; 12(1):594.

Malaria parasites form intracellular membranes that separate the parasite from the internal space of erythrocytes, and membrane proteins from the parasites are exported to the host via the membrane. In our previous study, Plasmodium vivax early transcribed membrane protein (PvETRAMP) 11.2, an intracellular membrane protein that is highly expressed in blood-stage parasites, was characterized as a highly immunogenic protein in P. vivax malaria patients. However, the other PvETRAMP family proteins have not yet been investigated. In this study, PvETRAMPs were expressed and evaluated to determine their immunological profiles.

Diverse Antibody Responses to Conserved Structural Motifs in Plasmodium falciparum Circumsporozoite Protein

January 15, 2020 - 07:51 -- Open Access
Pholcharee T, Oyen D, Torres JL, Flores-Garcia Y, Martin GM, González-Páez GE, Emerling D, Volkmuth W, Locke E, King CR, Zavala F, Ward AB, Wilson IA
J Mol Biol. 2019 Dec 27. pii: S0022-2836(19)30738-7

Malaria vaccine candidate RTS,S/AS01 is based on the central and C-terminal regions of the circumsporozoite protein (CSP) of P. falciparum. mAb397 was isolated from a volunteer in an RTS,S/AS01 clinical trial, and it protects mice from infection by malaria sporozoites. However, mAb397 originates from the less commonly used VH3-15 germline gene compared to the VH3-30/33 antibodies generally elicited by RTS,S to the central NANP repeat region of CSP. The crystal structure of mAb397 with an NPNA4 peptide shows that the central NPNA forms a type I β-turn and is the main recognition motif.

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