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    Microarray analyses reveal strain-specific antibody responses to Plasmodium falciparum apical membrane antigen 1 variants following natural infection and vaccination

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    Author
    Bailey, J.A.
    Berry, A.A.
    Travassos, M.A.
    Ouattara, A.
    Boudova, S.
    Dotsey, E.Y.
    Pike, A.
    Jacob, C.G.
    Adams, M.
    Takala-Harrison, S.
    Lyke, K.E.
    Laurens, M.B.
    Plowe, C.V.
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    Date
    2020
    Journal
    Scientific Reports
    Publisher
    Nature Research
    Type
    Article
    
    Metadata
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    See at
    https://doi.org/10.1038/s41598-020-60551-z
    Abstract
    Vaccines based on Plasmodium falciparum apical membrane antigen 1 (AMA1) have failed due to extensive polymorphism in AMA1. To assess the strain-specificity of antibody responses to malaria infection and AMA1 vaccination, we designed protein and peptide microarrays representing hundreds of unique AMA1 variants. Following clinical malaria episodes, children had short-lived, sequence-independent increases in average whole-protein seroreactivity, as well as strain-specific responses to peptides representing diverse epitopes. Vaccination resulted in dramatically increased seroreactivity to all 263 AMA1 whole-protein variants. High-density peptide analysis revealed that vaccinated children had increases in seroreactivity to four distinct epitopes that exceeded responses to natural infection. A single amino acid change was critical to seroreactivity to peptides in a region of AMA1 associated with strain-specific vaccine efficacy. Antibody measurements using whole antigens may be biased towards conserved, immunodominant epitopes. Peptide microarrays may help to identify immunogenic epitopes, define correlates of vaccine protection, and measure strain-specific vaccine-induced antibodies. Copyright 2020, The Author(s).
    Sponsors
    Howard Hughes Medical Institute, HHMI; National Institutes of Health, NIH: U01AI065683, R01HL130750, U19AI129386, R01AI093635, K23AI125720, T32AI007524, R21AI119733
    Keyword
    protein vaccines
    Antibodies
    Plasmodium falciparum
    Malaria Vaccines
    Identifier to cite or link to this item
    https://www.scopus.com/inward/record.uri?eid=2-s2.0-85080920956&doi=10.1038%2fs41598-020-60551-z&partnerID=40&md5=5f88f46110c2b22b97899b904d3d49d1; http://hdl.handle.net/10713/12232
    ae974a485f413a2113503eed53cd6c53
    10.1038/s41598-020-60551-z
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