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Active and passive protection of neonate piglets against respiratory and enteric viral infections

Contract nr: FAIR-CT96-1339
Project nr: 1339
Project type: SC
Starting date: 01/02/1997
Duration: 36 months
Total cost: 1,384,000 EUR
EC Contribution: 882,000 EUR
Scientific Officer: Isabel MINGUEZ-TUDELA
Research topic: Animal health
Acronym: PARENT

To protect new-born animals from enteric or respiratory infections, immediate intervention is required, when there is no time to induce an immune response. This type of infections, - like those caused by the enteric coronaviruses transmissible gastroenteritis virus (TGEV), porcine epidemic diarrhoea (PEDV), and rotaviruses - are responsible for mortality rates close to 100%. It is the key notion of this Project that protection can be provided in enteric and bronchial tissues by the administration of harmless bacteria and avirulent coronaviruses expressing virus-neutralising antibodies and protective antigens that will be synthesised in the appropriate mucosal surfaces.

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 neutralising 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 selectively express 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 almost instant expression of a neutralising 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:

1) immediate protection will be provided by the neutralising antibodies that will be produced as early as four hours after vector administration;

2) long-term protection will be induced by the immune response elicited by the vector itself or by antigens that will be co-expressed with the vector system.

Such immediate activity will overcome the fact that the new-born neonate piglet is very susceptible to respiratory and enteric infections, because of being born agammaglobulinemic and its having an immature systemic and mucosal immune system.

Keywords: piglets, PEDV, PRRSV, TGEV, mucosal immunity, iga, single-chain antibodies, filamentous haemagglutin, hemolysin.

CSIC - Consejo Superior de Investigaciones Cientificas
Campus de Cantoblano
E-28049 Madrid
Tel.: +34 91 585 45 36
Fax: +34 91 585 45 06


  • Henri SALMON
    Institut National de la Recherche Agronomique (I.N.R.A)
    Centre de Recherche de Tours-Nouzilly
    F-37380 Nouzilly
    Tel.: +33 2 47 42 78 91
    Fax: +33 2 47 42 77 79

  • Camille LOCHT
    Institut Pasteur de Lille Inserm
    Rue du Professeur Calmette 1
    B.P. 245
    F-59019 Lille
    Tel.: +33 3 20 87 77 28
    Fax: +33 3 20 87 79 06

    CSIC - Consejo Superior de Investigaciones Cientificas
    Campus de Cantoblano
    E-28049 Madrid
    Tel.: +34 91 585 45 35
    Fax: +34 91 585 45 06

    Fort Dodge Veterinaria SA (Formerly Laboratorios Sobrino)
    Ctra. de Camprodon s/n
    E-17813 Vall de Bianya, Gerona
    Tel.: +34 97 229 00 01
    Fax: +34 97 229 01 02
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