In Vivo Phase Variation and Serologic Response to Lipooligosaccharide of Campylobacter jejuni in Experimental Human Infection

摘要

Some Campylobacter jejuni strains which exhibit mimicry of gangliosides in their lipooligosaccharides (LOSs) are associated with development of Guillain-Barre syndrome, which complicates the selection of a suitable C. jejuni strain in a live-attenuated vaccine. C. jejuni 81-176 is the most well characterized strain available, but structurally, LOS of C. jejuni 81- 176 exhibits mimicry of predominantly GM2 and GM3 gangliosides. 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. jejuni vaccine, those of volunteers (22 following initial challenge and 5 upon rechallenge) experimentally infected with the homologous C. jejuni vaccine 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-GM1 and -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.