Determination of the vaccine potential of candidate Actinobacillus pleuropneumoniae proteins

Lead Research Organisation: University of Nottingham
Department Name: Div of Microbiology and Infectious Disea

Abstract

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Technical Summary

This project is concerned with the bacterium Actinobacillus pleuropneumoniae (APL). This causes a severe, often fatal, lung infection in pigs, which can be economically devastating for the pig-rearing industry. At present there is no effective licensed vaccine to prevent infection. This project aims to assess the vaccine potential of seven novel protein candidates which we have previously identified and characterised using BBSRC funding. We shall employ robust techniques including vaccination and challenge studies to pigs in this proof-of-principle study. The information gained will be the key to securing industry funding and will help improve the effectiveness of future vaccines. This will have an impact on the pig rearing industry by increasing wealth creation and lowering the disease burden of commercially raised pigs. This research will be undertaken at the University of Nottingham and at the Royal Veterinary College in conjunction with Imperial College, London.
 
Description This project was concerned with the bacterium Actinobacillus pleuropneumoniae (APL). This causes a severe, often fatal, lung infection in pigs, which can be economically devastating for the pig-rearing industry. At present, there is no effective licensed vaccine to prevent infection. This project aimed to determine the vaccine potential of seven Actinobacillus pleuropneumoniae proteins. These were tested for their ability to induce an immunological response in the pig and protect against homologous challenge using an established pig challenge model. Overall, the results suggest that none of the candidates gave significant protection against invasive disease (measured by clinical sepsis and lung macroscopy). There may be several explanations for these findings. For example, the recombinant proteins were denatured, and thus may have lost conformational epitopes that might have been protective; or the vaccinations failed to elicit protective antibody responses. In the absence of a suitable in-vitro correlate of protection assay, immunoblot and ELISA analysis were carried out and they confirmed that all groups tested demonstrated post-vaccination increases in APL-specific serum IgG antibody titers. However, this antibody response did not correlate with the observed clinical syndromes in the test and control groups. Furthermore, for ethical and economic reasons we used a small number of animals. Unfortunately, as a consequence, we were unable to undertake thorough statistical analysis of our results. A larger, statistically significant study using more animals in each group would allow a clearer picture of the protective efficacy of the vaccines to be established. Additional studies using combinations of the candidate proteins may show that these elicit improved protection compared with individual proteins. In the light of the discouraging results, we intend to review our approach and for future trials we might seek industrial partners.
Exploitation Route Could be used by companies developing vaccines against APL to inform decisions on the suitability of candidate antigens for testing. This research has shown that the seven antigens tested (at least in the form used in this study) do not protect animals against homologous challenge using an established pig challenge model. Therefore, these antigens are unlikely to be commercially exploitable, and our work perhaps also emphasizes that combinations of antigens may have to be used to obtain optimal protection.
Sectors Agriculture

Food and Drink
 
Description In the light of the discouraging results, we have not taken this project forward.
Sector Agriculture, Food and Drink