Live virulentRhodococcus equi, rather than killed or avirulent, elicits protective immunity toR. equiinfection in mice

Abstract

Mice inoculated intravenously with a sublethal dose of live virulent Rhodococcus equi ATCC 33701 that contained an 85-kb virulence plasmid were immune to a lethal intravenous challenge of ATCC 33701. This immunity depended upon the dose of immunization and developed rapidly: mice primed with 10(5) live ATCC 33701 eliminated the challenged bacteria more rapidly than mice primed with doses ranging from 10(2) to 10(4) bacteria, and mice given 10(5) live ATCC 33701 intravenously withstood the lethal challenge as early as 5 days after the initial inoculation. However, this protective immunity did not develop in mice immunized with doses of heat-killed ATCC 33701 ranging from 10(6) to 10(8), or in mice immunized with doses of live ATCC 33701P-, a plasmid-cured derivative (avirulent), in doses ranging from 10(5) to 10(7). These mice had positive antibody titers against R. equi at the challenge (14 days after priming). Adoptive transfer of resistance to virulent R equi was obtained with spleen cells from mice immunized with live ATCC 33701, but not monoclonal antibody to 15- to 17-kDa virulence-associated antigens. These results revealed that live ATCC 33701P-, a plasmid-cured derivative of virulent R equi, could not elicit protective immunity, and are consistent with previous observations that protective immunity was induced by live virulent, but not killed organisms.

Enteral immunization with live bacteria reprograms innate immune cells and protects neonatal foals from pneumonia

“…A previous vaccine trial using gavage of inactivated R. equi failed to protect foals against pneumonia, despite induction of a R. equi -specific cell-mediated immune response and local IgA ( 24 ). Immunization in mice with live virulent R. equi , but not killed or avirulent R. equi , also elicits protective immunity against R. equi ( 73 ). For other bacteria known to induce trained immunity, such as BCG vaccine strains and Shigella , inactivation weakened or abrogated the training of innate immune cells ( 50, 74 ).…”

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“…Methods for preventing R. equi pneumonia include chemoprophylaxis, vaccination, and administration of hyperimmune plasma (HIP) [13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30]. Of these, the only USDA-approved and well-established method for reducing the incidence of R. equi pneumonia is transfusion of HIP from equine donors hyperimmunized against R. equi (RE HIP) [13][14][15]17].…”