DNA immunization of pigs with foot-and-mouth disease virus minigenes

One of the main challenges in animal health research is developing new and more effective and safer recombinant vaccines against foot-and-mouth disease (FMD), one of the most contagious and economically devastating diseases for ungulates. Researchers of the CReSA, INIA and CBMSO have published in Virus Research the last results obtained with DNA vaccines.

FMD is one of the most contagious and economically devastating diseases for animal health that affects several species of cloven-hoofed wild and farm animals. The high genetic variability of Foot-and-mouth disease virus (FMDV), together with its highly contagious nature complicates the successful control of FMD. The currently available conventional vaccines, based on chemically inactivated virus, pose several disadvantages including safety issues and the narrow antigenic spectrum they cover. Therefore there is a growing demand for the development of novel and safe marker vaccines against FMDV.

DNA immunization is one of the most promising choices accomplishing the above mentioned requisites, thus becoming an attractive vaccination approach for swine and other veterinary species. Regarding FMDV, several attempts have been made to develop effective DNA vaccines in small animal models and in the natural FMDV hosts. Despite several attempts to design new vaccines, there are as of yet no available alternatives to the conventional FMDV vaccines.

Researchers of the Centre de Recerca en Sanitat Animal (CReSA, UAB-IRTA), Centro de Investigación en Sanidad Animal (CISA-INIA), Departamento de Biotecnología (INIA) and Centro de Biología Molecular Severo Ochoa (CBMSO, CSIC-UAM), have carried out a collaborative work aiming to obtain recombinant vaccines against FMDV based on DNA immunization strategies.

In a previous study we showed that DNA vaccines encoding FMDV B and T cell epitopes, either alone (pCMV-BTT) or fused to a signal peptide (pCMV-spBTT), partially protected mice from FMDV challenge. Here, we present the divergent results obtained in pigs after immunization with these two experimental DNA vaccines encoding one B and two T cell FMDV epitopes.

The main conclusions of this study are:

  1. While all pigs vaccinated with pCMV-spBTT showed both a delay in the disease onset and reduced severity of signs and lesions after FMDV challenge, pigs immunized with pCMV-BTT showed an exacerbation of the disease and most of the pigs remained viremic at 10 days post-infection, the end-point of the experiment, thus opening concerns about FMDV-suboptimal immunization.
  2. Interestingly, only one of the four pigs vaccinated with pCMV-spBTT showed neutralizing antibodies before challenge, demonstrating that partial protection against FMDV could be afforded in the absence of preexisting neutralizing antibodies.

We are currently extending these studies aiming to understand the intrinsic mechanisms that explain the different outcomes induced by our two vaccines. The observation that the same FMDV epitopes can induce such different immune responses, open new possibilities for FMDV vaccine designing, but also poses concerns about vaccination against this disease.

This paper has been recently published in: Ganges L, Borrego B, Fernández-Pacheco P, Revilla C, Fernández-Borges N, Domínguez J, Sobrino F, Rodriguez F. DNA immunization of pigs with foot-and-mouth disease virus minigenes: From partial protection to disease exacerbation. Virus Res. 2011 Apr;157(1):121-5.

To contact with the authors of the paper at the CReSA:

Dr Llilianne Ganges Espinosa
Researcher in charge of the Classical Swine Fever research line of the CReSA
Email: llilianne.ganges@cresa.uab.cat
Telephone no.: (+34) 935814620
Fax: (+34) 935814490
Edifici CReSA. Campus UAB
08193 Bellaterra (Barcelona) Spain

Dr Fernando Rodríguez González
Researcher in charge of the African Swine Fever research line of the CReSA
Edifici CReSA. Campus UAB
08193 Bellaterra (Barcelona) Spain
Email: fernando.rodriguez@cresa.uab.cat
Telephone no.: +34 93 581 45 62
Fax: +34 93 581 44 90

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