Mycoplasma pneumoniae reinfection and vaccination: protective oral vaccination and harmful immunoreactivity after re-infection and parenteral immunization

Abstract

Animal model studies of Mycoplasma pneumoniae infection after live respiratory challenge were conducted to investigate the issues of challenge-rechallenge associated accentuated pathology, postparenteral vaccination associated accentuated pathology, and oral vaccination. Live M. pneumoniae inocula were grown in hamster serum-based medium in order to reduce the potential for the serum growth component to participate in the hyperaccentuated histopathological response as seen with challenge-rechallenge experiments which have used horse serum-based growth media. Despite the use of homologous animal serum, an early hyperaccentuated response occurred (day 3 score 13.3 vs day 10 score 7.7; P=0.02) which included perivascular infiltrates, and histopathological scores for early (day 3) and late (day 10) disease were similar ( P>0.10) between experiments of challenge-rechallenge when either homologous or heterologous sera were used in inoculum growth media. Parenteral vaccination with heat-killed bacteria also led to an early hyperaccentuated histopathological response after live respiratory challenge (scores on day 3: vaccinated 18.3, unvaccinated 6.2; P<0.01) and this response was not significantly diminished when inocula were cleaned of growth medium components. An early accentuated response did not follow oral vaccination with heat-killed bacteria (score on day 3: vaccinated 5.7) and the late reaction was significantly less after challenge (scores on day 10: vaccinated 10.3, unvaccinated 14.6; P=0.011). Studies of parenteral vaccination should include analyses for early disease after live challenge. Oral vaccination offers a promising route for stimulating protective immunity while minimizing undesirable recall immune events.