Abstrakt: |
ABSTRACTSome Campylobacter jejunistrains which exhibit mimicry of gangliosides in their lipooligosaccharides (LOSs) are associated with development of Guillain-Barré syndrome, which complicates the selection of a suitable C. jejunistrain in a live-attenuated vaccine. C. jejuni81-176 is the most well characterized strain available, but structurally, LOS of C. jejuni81-176 exhibits mimicry of predominantly GM2and GM3gangliosides. We compared the antiganglioside human serologic responses of 22 volunteers post-oral vaccination (two-dose series, 14 days apart) with a killed whole-cell C. jejunivaccine, those of volunteers (22 following initial challenge and 5 upon rechallenge) experimentally infected with the homologous C. jejunivaccine strain 81-176, and those of 12 volunteers used as controls (placebo recipients). All volunteers were evaluated using thin-layer chromatography immuno-overlay and a panel of nine gangliosides at days 0, 21, and 28 either postvaccination or postinoculation. Antiganglioside antibodies were identified at baseline in 6 of the 61 volunteers (9.8%). There were no antiganglioside antibodies observed following vaccination or experimental infection rechallenge. Evidence of seroconversion was observed in 2 of 22 (9.1%) in the initial infection challenge group, comparable to 1 of 12 (8.3%) in the placebo recipients. Additional testing of seven selected volunteers in the initial challenge group at days 0, 3, 7, 10, 21, 28, and 60 showed that when antiganglioside antibodies occurred (mostly anti-GM1and -GM2), responses were weak and transient. Furthermore, evidence from serologic probing of LOSs of isolates recovered from stools of six volunteers indicated that the isolates had undergone antigenic phase variation in ganglioside mimicry during passage in vivo. Collectively, with the exception of one volunteer with anti-GM2antibodies at day 60, the results show an absence of persistent antiganglioside antibodies after experimental infection with C. jejunior following administration of a killed C. jejuniwhole-cell oral vaccine, although LOS phase variation occurred. |