title: Anti-microbial peptide gene expression during oral vaccination: analysis of a randomized controlled trial.
abstract: We have observed previously that micronutrient supplementation ameliorated suppression of α-defensin expression during diarrhoea. However, how interactions between anti-microbial peptide (AMP) expression and diarrhoeal disease are altered by micronutrient supplementation remain unclear. Using oral vaccination as a model of intestinal infection, we measured changes in AMP expression during multiple micronutrient supplementation. In the first part, volunteers underwent duodenal jejunal biopsy before and at 1, 2, 4 or 7 days after administration of one of three live, attenuated oral vaccines against rotavirus, typhoid and enterotoxigenic Escherichia coli. In the second part, participants were randomized to receive a multiple micronutrient supplement or placebo for 6 weeks before undergoing intestinal biopsy, vaccination against typhoid and rebiopsy after 14 days. Expression of human alpha-defensin (HD)5, HD6, hBD1, hBD2 and LL-37 was measured by quantitative reverse transcription-polymerase chain reaction. Taken together, the bacterial vaccines, but not rotavirus vaccine, reduced HD5 expression (P = 0·02, signed-rank test) and reduced LL-37 expression in seven of the eight individuals whose biopsies had expression prevaccination (P = 0·03). hBD2 was not detected. In the controlled trial, HD5 and HD6 expression after vaccination was lower [median ratio 0·5, interquartile range (IQR) = 0·07-2·2 and 0·58, IQR = 0·13-2·3, respectively] than before vaccination. There was no significant effect detected of micronutrient supplementation on expression of HD5, HD6, hBD1 or LL-37. We conclude that live attenuated bacterial vaccines, but not rotavirus vaccine, can reduce intestinal α-defensins, and typhoid vaccine reduced LL-37 expression. We found no evidence that micronutrient supplementation in the short term had any impact on anti-microbial peptide expression.
authors.affiliation: Tropical Gastroenterology and Nutrition Group, University of Zambia School of Medicine, Lusaka, Zambia.|Programme for the Awareness and Elimination of Diarrhoea (PAED), Centre for Infectious Disease Research in Zambia.
authors.forename: M
authors.initials: M
authors.lastname: Simuyandi
authors.affiliation: Tropical Gastroenterology and Nutrition Group, University of Zambia School of Medicine, Lusaka, Zambia.|Biological Sciences Department, School of Natural Sciences, University of Zambia, Lusaka, Zambia.
authors.forename: M
authors.initials: M
authors.lastname: Kapulu
authors.affiliation: Tropical Gastroenterology and Nutrition Group, University of Zambia School of Medicine, Lusaka, Zambia. m.p.kelly@qmul.ac.uk.|Barts and the London School of Medicine, London, UK. m.p.kelly@qmul.ac.uk.
authors.forename: P
authors.initials: P
authors.lastname: Kelly
keywords: anti-microbial peptides; defensins; micronutrients; oral vaccines; zinc