This Proposal deals with a novel methodology for the early protection of neonate piglets against mucosal infections caused by the porcine epidemic diarrhoea virus (PEDV) and the porcine reproductive and respiratory syndrome virus (PRRSV), by targeting the expression of recombinant antibodies to mucosal areas and by inducing mucosal immune responses. Short-term passive protection will be achieved by administration of viral or bacterial vectors that secrete in situ neutralizing antibodies into the intestinal and bronchial mucosae. Longer-term active protection will be further developed with the use of the same vectors for presentation of selected viral antigens to the bronchial-associated or the gut-associated lymphoid tissues of both mucosal niches.
The basis of this Proposal is our current ability to express selectively recombinant antibodies and protective antigens in either the respiratory or in the enteric tract of pigs by means of bacterial carriers that naturally target these niches (Bordetella bronchiseptica and Escherichia coli, respectively) or by the use of innocuous derivatives of the transmissible gastroenteritis virus (TGEV) engineered to have a controlled respiratory or intestinal tropism. For the bacterial-based systems, we will exploit the export machinery of the filamentous haemagglutin of Bordetella and the hemolysin export system of E. coli to release, respectively, single-chain anti-PRRSV or anti-PEDV antibodies and relevant antigens into the respiratory or the intestinal tract. The main tool for the nearly instant expression of a neutralizing activity in the same niches will be the use of TGEV-derived constructs with various degrees of autonomous replication and engineered to produce full-size recombinant antibodies. In either case (bacterial or viral carriers), protection will be elicited through two complementary mechanisms : [11 Immediate protection will be provided by the neutralizing antibodies that will be produced as early as 4 h after vector administration, and  Long-term protection will be induced by the immune response elicited by the vector itself or by antigens that will be coexpressed with the vector system. Such an immediate activity will overcome the fact that the neonate piglet is very susceptible after birth to respiratory and enteric infections, because of its being born agammaglobulinemic and its having an immature systemic and mucasal immune system.
Keywords : Piglets, PEDV, PRRSV, TGEV, mucosal immunity, IgA, single-chain antibodies, filamentous haemagglutin, hemolysin.
Funding SchemeCSC - Cost-sharing contracts
17813 Vall De Bianya, Gerona