DiaPep277 May Work Orally to Assist
Conversion of Helper to Suppressor Th2 Cells
in Models of Type 1 Diabetes

S. Brugman1, J. Visser1, F. Klatter1, D. Elias2, N. Bos1, J. Rozing1;
1Cell Biology, University of Groningen, Groningen, Netherlands, 2Peptor Ltd., Revohot, Israel.

Background and Aims: Diabetes Type 1 is an autoimmune disease that leads to the destruction of
insulin-producing ß-cells in the islets of Langerhans in the pancreas. The identity of the target self-antigen
is not known. Several self-antigens have been reported to be involved in activating T-cells to destroy the
islets. Hsp60 is one of those self-antigens. Heat shock proteins are found in all life forms and are highly
conserved. Hsp60 (the human equivalent of bacterial hsp65) has been implicated in autoimmunity through
molecular mimicry, based on the high homology with hsp65 of microorganisms leading to recognition of
the hsp60 and consequent reaction of the immune system. DiaPep277 is composed of a 24-amino-acid
sequence of hsp60. NOD mice spontaneously developing diabetes manifest progressive T-cell reactivity
to p277 beginning at the onset of insulitis. The objective of the present study was to test whether it was
possible to affect diabetes development by neonatal oral administration of DiaPep277 in two models of
diabetes; the BB-DP rat model and BB-DP rats on a hydrolysed casein (HC) diet, which gives partial
protection against diabetes.
Materials and Methods: Neonatal BB-DP rats received orally either DiaPep277 in saline or saline on day
4, 5, 6, and 7 of life (300 µg/rat/day). After weaning, rats received either standard laboratory chow or HC
diet.
Results: The group that received DiaPep277 and standard chow showed a lower diabetes incidence
(69% DiaPep277 versus 86% in control). The DiaPep277 and HC diet group showed an even lower
incidence (31% Diapep277 + HC compared to 53% in control + HC). As previously reported, groups that
received HC diet showed a delay in onset of diabetes (from the age of 60 days in the control groups to an
average 80 days in the HC groups). Analysis of the intestinal flora of the animals showed a significant
increase in Eubacterium sp. in the HC groups. No differences were found between the groups receiving
DiaPep277 or saline.
Conclusion: While HC diets could have their protective effects by changing the composition of intestinal
microflora, DiaPep277 could have its effect through induction of oral tolerance.

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