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Orally fed seeds producing designer IgAs protect weaned piglets against enterotoxigenic Escherichia coli infection
- Virdi, Vikram, Coddens, Annelies, De Buck, Sylvie, Millet, Sam, Goddeeris, Bruno Maria, Cox, Eric, De Greve, Henri, Depicker, Ann
- Proceedings of the National Academy of Sciences of the United States of America 2013 v.110 no.29 pp. 11809-11814
- Arabidopsis thaliana, antibodies, bacterial shedding, diarrhea, enterocytes, enterotoxigenic Escherichia coli, farming systems, financial economics, immune response, immunization, immunoglobulin A, immunoglobulin G, industry, llamas, pathogens, piglets, seed extracts, seeds, weight gain
- 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.