Avid binding by B cells to the Plasmodium circumsporozoite protein repeat suppresses responses to protective subdominant epitopes

Deepyan Chatterjee, Fiona J. Lewis, Henry J. Sutton, Joe A. Kaczmarski, Xin Gao, Yeping Cai, Hayley A. McNamara, Colin J. Jackson, Ian A. Cockburn*

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    19 Citations (Scopus)

    Abstract

    Antibodies targeting the NANP/NVDP repeat domain of the Plasmodium falciparum circumsporozoite protein (CSPRepeat) can protect against malaria. However, it has also been suggested that the CSPRepeat is a decoy that prevents the immune system from mounting responses against other domains of CSP. Here, we show that, following parasite immunization, B cell responses to the CSPRepeat are immunodominant over responses to other CSP domains despite the presence of similar numbers of naive B cells able to bind these regions. We find that this immunodominance is driven by avid binding of the CSPRepeat to cognate B cells that are able to expand at the expense of B cells with other specificities. We further show that mice immunized with repeat-truncated CSP molecules develop responses to subdominant epitopes and are protected against malaria. These data demonstrate that the CSPRepeat functions as a decoy, but truncated CSP molecules may be an approach for malaria vaccination.

    Original languageEnglish
    Article number108996
    JournalCell Reports
    Volume35
    Issue number2
    DOIs
    Publication statusPublished - 13 Apr 2021

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