Improvement of the systemic prime/oral boost strategy for systemic and local responses.

This paper describes oral boost immunisations of primed animals as an alternative oral vaccination strategy. Mice were primed orally (PO), intranasally (IN), subcutaneously (SC), or intraperitoneally (IP) with ovalbumin (OVA) with or without adjuvant. Boost immunisations were given orally with or without cholera toxin (CT) as adjuvant. Prime immunisations induced variable IgA and IgG(1) titres in serum depending on the route. A subsequent oral boost increased these titres. Use of an adjuvant in the priming significantly increased serum IgA and, to a lesser extend, IgG(1). Oral boost immunisation induced significantly higher serum IgA titres in animals primed via the SC, IP and the IN route compared to the PO route. This was independent of the use of CT. Three oral boosts with OVA plus 5 microg CT given in 5 days to primed mice revealed higher IgA titres compared to single oral boosts and anti-OVA IgA titres in faeces were also detected. Finally, we put together our findings and propose a systemic priming/oral boost strategy in which mice were primed via the SC route with 100 microg OVA plus 50 microg Butyl16-p(AA), and subsequently orally boosted with three doses of 300 microg OVA plus 5 microg CT each. We concluded that oral immunisation is more effective in IN, SC, or IP primed mice than in PO primed mice, and that the IgA antibody response in serum and faeces can be improved by increasing the immunisation frequency and the use of appropriate adjuvants in primary and boost immunisation. The here-formulated strategy improves the probability of success of oral vaccination. The results are discussed in the light of the development of edible vaccines.

Efficacy of oral administration and oral intake of edible vaccines.

To evaluate whether vaccine administration via intragastric gavage is indicative for the outcome of edible vaccines, mice were orally immunised with ovalbumin (OVA) mixed with or without Vibrio cholerae toxin (CT) in various compositions via various routes: (1) OVA dissolved in saline and intragastrically (IG) administered ('IG'); (2) OVA mixed with food extract and administered IG ('food IG'); (3) food chow absorbed with OVA dissolved in saline and fed to the animals ('food'); and (4) OVA dissolved in saline and administered via drinking bottles ('drinking'). When given to naive mice, 'IG' and 'food IG' but not 'food' or 'drinking' induced anti-OVA IgG1 responses in serum, but oral boost immunisations were necessary. Serum IgA was not induced. Oral boosting of subcutaneously (SC) primed mice enhanced the IgG1 and IgA response in serum regardless of the route of immunisation or the vaccine composition. CT did not dramatically enhance the immune response. All immunisation routes except 'drinking' induced antigen-specific IgA antibody secreting cells (ASC) in the lamina propria of naive mice. But antigen-specific antibody responses in faeces were not observed. We concluded that oral (i.e. IG) administration is distinct from oral intake. The composition of the vaccine (food or saline) did not influence oral administration. We thus suggested that the route of administration greatly influenced the outcome of oral immunisation. Although oral administration is a well-accepted route to test the potentials of oral vaccines, our study demonstrated that it is merely indicative for the effectiveness of edible vaccines. Studies on the feasibility of edible vaccines should thus be performed by eating the vaccine.