A reverse vaccinology approach to swine dysentery vaccine development

Swine dysentery (SD) is a mucohaemorrhagic colitis of pigs resulting from infection of the large intestine with the anaerobic intestinal spirochaete <i>Brachyspira hyodysenteriae</i>. Whole-cell bacterin vaccines are available to help control SD, but their performance has been inconsistent. This study aimed to use a reverse vaccinology approach to identify <i>B. hyodysenteriae</i> proteins for use as recombinant vaccine components. Nineteen open reading frames (ORFs) predicted to encode potential vaccine candidate molecules were identified from <i>in silico</i> analysis of partial genomic sequence data. The distribution of these ORFs among strains of <i>B. hyodysenteriae</i> was investigated by PCR, and widely distributed ORFs were cloned. The products were screened with a panel of immune pig sera, and from these a subset of conserved, immunogenic proteins was selected. Mice immunized intramuscularly with these recombinant proteins developed specific systemic antibody responses to them, and their sera agglutinated <i>B. hyodysenteriae</i> cells <i>in vitro</i>. In a pilot experiment, eight pigs were vaccinated twice intramuscularly with a combination of four of the proteins. The pigs developed antibodies to the proteins, and following experimental challenge only one developed SD compared to five of nine non-vaccinated control pigs. Although these differences in incidence were not significant, they indicated a trend towards protection using the recombinant proteins as immunogens. This study demonstrates that the reverse vaccinology approach has considerable potential for use in developing novel recombinant vaccines for SD.