Cyclic enterobacterial common antigens fromEscherichia coliO157 as microbe-associated molecular patterns

In a previous study, we described 2 forms of cyclic enterobacterial common antigen (ECACYC), a tetramer and a pentamer, from Escherichia coli O157. ECACYC is present in several representatives of the Enterobacteriaceae. To date, functional studies on ECACYC are sparse. Cyclic oligosaccharides in other bacteria, like the cyclic -glucans in Rhizobiaceae, represent microbe-associated molecular patterns involved in host–bacteria interaction. This observation determined the aim of the present study: to test whether the tetrameric and pentameric ECACYC from E. coli O157 can be recognised by host humoral and cellular mechanisms. ELISA tests designed to compare the 2 ECACYC with the O157 lipopolysaccharide showed that both ECACYC were not recognised by polyclonal anti-O157 serum but were good ligands for mannan-binding lectin. The lectin had a higher affinity for the tetramer than the pentamer. ECACYC deposited more C3b than did the lipopolysaccharide. To examine the interactions with human circulating neutrophils, the antigens were loaded onto fluorescent latex beads and applied in a phagocytosis experiment. Spheres coated with the 2 ECACYC occasionally adhered to phagocyte surfaces but, unlike O157-loaded spheres, failed to induce free-radical release. The results show that the 2 ECACYC represent microbe-associated molecular patterns recognised by host humoral non-self-recognition mechanisms

Prior flavivirus immunity skews the yellow fever vaccine response to cross-reactive antibodies with potential to enhance dengue virus infection

Abstract The yellow fever 17D vaccine (YF17D) is highly effective but is frequently administered to individuals with pre-existing cross-reactive immunity, potentially impacting their immune responses. Here, we investigate the impact of pre-existing flavivirus immunity induced by the tick-borne encephalitis virus (TBEV) vaccine on the response to YF17D vaccination in 250 individuals up to 28 days post-vaccination (pv) and 22 individuals sampled one-year pv. Our findings indicate that previous TBEV vaccination does not affect the early IgM-driven neutralizing response to YF17D. However, pre-vaccination sera enhance YF17D virus infection in vitro via antibody-dependent enhancement (ADE). Following YF17D vaccination, TBEV-pre-vaccinated individuals develop high amounts of cross-reactive IgG antibodies with poor neutralizing capacity. In contrast, TBEV-unvaccinated individuals elicit a non-cross-reacting neutralizing response. Using YF17D envelope protein mutants displaying different epitopes, we identify quaternary dimeric epitopes as the primary target of neutralizing antibodies. Additionally, TBEV-pre-vaccination skews the IgG response towards the pan-flavivirus fusion loop epitope (FLE), capable of mediating ADE of dengue and Zika virus infections in vitro. Together, we propose that YF17D vaccination conceals the FLE in individuals without prior flavivirus exposure but favors a cross-reactive IgG response in TBEV-pre-vaccinated recipients directed to the FLE with potential to enhance dengue virus infection