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.