If induction of oral immunity requires that the antigen traverse the gut wall, it may be that despite administering OVA for 9 days to lambs in Group C, only the first 2�C3 doses traversed the gut wall and led to induction of oral immunity. Experiments are underway together to elucidate the kinetics of gut permeability and the impact this has on the mechanisms of antigen uptake and where antigen presentation to lymphocytes occurs (i.e. in the Peyer��s patches, isolated lymphoid follicles, or mesenteric lymph nodes). Should future studies show that early life oral vaccination consistently promotes oral immunity, it will have important implications for protecting against infectious diseases in the very young and it may reduce the number of carriers of disease-producing organisms within a herd.

In contrast to the immune response induced in neonatal lambs gavaged with OVA over a 9 day period immediately after birth, a single high dose exposure to antigen appeared to promote a trend towards induction of oral tolerance in lambs. Our results suggest that inappropriate induction of oral tolerance to an antigen may impede the host from generating an immune response to this antigen in the future. These results corroborate what was observed by Buddle et al. (2002) wherein it was observed that already at 6 weeks of age, calves had been naturally exposed to mycobacterial antigens [33]. As adults, the cattle with pre-existing responses to environmental mycobacteria were much less responsive to vaccination than were na?ve adult cattle [33].

Further experiments must be performed to clearly determine whether in fact, as our data appears to indicate, Cilengitide early-life antigen exposure in lambs also negatively impacts future response to vaccination. Should this prove to be the case, it will be critical to establish 1) whether a parenteral vaccine can be administered to circumvent or reverse the tolerogenic response, or 2) whether it is advisable to proactively orally vaccinate neonates prior to environmental exposure to preserve their ability to promote an immune response to later pathogen or vaccine exposure events. Conclusions In the present study, we determined that repeated low dose oral administration of OVA for 9 days of age starting the day after birth induced priming of the immune system, not oral tolerance. In contrast, a single, higher dose oral exposure in neonatal lambs promoted what appeared to be a tolerogenic response which negatively impacted the immune response to parenteral vaccination in later life. We conclude that neonatal lambs are receptive to either induction of immunity or oral tolerance if exposed to antigen in the period immediately after birth, depending on the dose and/or kinetics of exposure.