Fasting before Intra-Gastric Dosing with Antigen Improves Intestinal Humoral Responses in Syrian Hamsters

Abstract

Oral vaccines, unlike injected, induce intestinal secretory immunoglobulin A (sIgA) mimicking our natural defense against gut pathogens. We previously observed sIgA responses after administering the Clostridioides difficile colonisation factor CD0873 orally in enteric capsules to hamsters. Enteric-coated capsules are designed to resist dissolution in the stomach and disintegrate only at the higher pH of the small intestine. However, the variable responses between animals led us to speculate suboptimal transit of antigens to the small intestine. The rate of gastric emptying is a controlling factor in the passage of oral drugs for subsequent availability in the small intestine for absorption. Whilst in humans, food delays gastric emptying, in rats, capsules can empty quicker from fed stomachs than from fasted. To test in hamsters if fasting improves the delivery of antigens to the small intestine, as inferred from the immune responses generated, 24 animals were dosed intragastrically with enteric capsules containing recombinant CD0873. Twelve hamsters were fasted for 12 h prior to each dose and the other 12 fed. Significantly higher sIgA titres, with significantly greater bacterial-adherence-blocking activity, were detected in small intestinal lavages in the fasted group. We conclude that fasting in hamsters improves intestinal delivery leading to more robust responses.

Keywords

• oral vaccines
• <i>Clostridioides difficile</i>
• intestinal delivery
• fasting
• secretory IgA