Genetic immunisation with bovine beta-lactoglobulin cDNA induces a preventive and persistent inhibition of specific anti-BLG IgE response in mice

Background. Various studies have shown that DNA immunisation with gene alle rgen induces a non-allergic response. Methods: We applied this new type of vaccination to bovine beta -lactoglobulin (BLG), a major cow's milk allerge n, using a plasmid that allows the production of a partially secreted prote in. Specific antibodies and cytokines were quantified in different immunisa tion protocols. Results: The primary response in mice immunised with BLG-en coding plasmid (pBLG) is of the Th1 type. Restricted recognition of a nativ e form of BLG in pBLG mice contrasted with a broader range of recognition i n BLG-in-alum-immunised mice, notwithstanding the fact that alum favours th e presentation of a native form of the antigen. We also demonstrated an inh ibitory effect of pDNA immunisation on the Th2 response induced by a subseq uent immunisation using BLG adsorbed on alum. However, this preventive effe ct is highly dependent on the time of pre-administration of the pBLG, with an optimal effect when pDNA immunisation occurred at least 21 days before p rotein administration. This preventive effect resulted concomitantly in the inhibition of BLG-specific IgE, in the induction of specific IgG2a, and in the decrease of the specific IgG1/IgG2 ratio. It is accompanied by an incr ease in IFN gamma and IL-10 secretion. Moreover, the preventive effect was shown to be persistent even after a booster immunisation with alum-adsorbed BLG. The Th1 orientation of the response is very likely due to the present ation of the protein in theTh1 environment due to plasmid immunostimulatory sequences, as intramuscular injection of BLG itself leads to a weak Th2 re sponse and had no preventive effect on a subsequent sensitisation. Conclusi on: This study further demonstrates the potential use of DNA immunisation f or prevention of IgE response, but the window of action seems to be very re stricted if we are to inhibit an established Th2 response efficiently. Copy right (C) 2001 S. Karger AG, Basel.