Orally fed seeds producing designer IgAs protect weaned piglets against enterotoxigenic Escherichia coli infection

Vikram Virdi, Annelies Coddens, Sylvie De Buck, Sam Millet, Bruno Maria Goddeeris, Eric Cox, Henri De Greve, Ann Depicker

    Onderzoeksoutput: Bijdrage aan tijdschriftA1: Web of Science-artikel

    Uittreksel

    Oral feed-based passive immunization can be a promising strategy to prolong maternal lactogenic immunity against postweaning infections. Enterotoxigenic Escherichia coli (ETEC)-caused postweaning diarrhea in piglets is one such infection that may be prevented by oral passive immunization and might avert recurrent economic losses to the pig farming industry. As a proof of principle, we designed anti-ETEC antibodies by fusing variable domains of llama heavy chain-only antibodies (VHHs) against ETEC to the Fc part of a porcine immunoglobulin (IgG or IgA) and expressed them in Arabidopsis thaliana seeds. In this way, four VHH-IgG and four VHH-IgA antibodies were produced to levels of about 3% and 0.2% of seed weight, respectively. Cotransformation of VHH-IgA with the porcine joining chain and secretory component led to the production of light-chain devoid, assembled multivalent dimeric, and secretory IgA-like antibodies. In vitro analysis of all of the antibody-producing seed extracts showed inhibition of bacterial binding to porcine gut villous enterocytes. However, in the piglet feed-challenge experiment, only the piglets receiving feed containing the VHH-IgA-based antibodies (dose 20 mg/d per pig) were protected. Piglets receiving the VHH-IgA-based antibodies in the feed showed a progressive decline in shedding of bacteria, significantly lower immune responses corroborating reduced exposure to the ETEC pathogen, and a significantly higher weight gain compared with the piglets receiving VHH-IgG producing (dose 80 mg/d per pig) or wild-type seeds. These results stress the importance of the antibody format in oral passive immunization and encourage future expression of these antibodies in crop seeds.
    TaalEngels
    TijdschriftProceedings of the National Academy of Sciences of the United States of America
    Volume110
    Exemplaarnummer29
    Pagina's (van-tot)11809-11814
    Aantal pagina's6
    ISSN0027-8424
    DOI's
    StatusGepubliceerd - 2013

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