FLAGELLIN H7 AS A POTENTIAL VACCINE COMPONENT TO PREVENT HEMOLYTIC UREMIC SYNDROME

ALAN MAURO BERNAL; FERNANDO NICOLÁS SOSA; MARÍA FLORENCIA TODERO; MONICA VERMEULEN; DANIELA ROMINA MONTAGNA; ROMINA JIMENA FERNÁNDEZ-BRANDO; MARÍA VICTORIA RAMOS; AGUSTINA ERREA; MARTÍN RUMBO; MARINA SANDRA PALERMO

Exposici�n; Reunión Anual de Sociedades de Biociencias; 2022

Argentina has the highest global incidence of hemolytic uremic syndrome (HUS), asystemic complication secondary to Escherichia coli O157:H7 (EHEC) infections. Localhumoral response plays a key role in controlling intestinal colonization of EHEC andpreventing HUS. Thus, the objective of this work was to analyze the ability of flagellinH7 (H7) to induce a local protective response. For this, BALB/c mice were intranasallyimmunized with 3 doses of purified H7 (10 µg/mouse) at 10-day intervals. At differenttimes, stools and serum samples were taken to analyze the levels of anti-H7 antibodiesby ELISA. 21 days post 3 rd immunization (dp3i) we studied ex vivo the specificproliferation of CFSE-stained lymphocytes from spleen (S) and lung-draining lymphnodes (LN) of immunized mice versus controls. The production of cytokines wasmeasured in the proliferation supernatants to determine Th1/Th2/Th17 profile. Toassess protection, immunized and control mice were challenged orally with 10 5 colony-forming units of EHEC 21 dp3i. We observed significant levels of IgG and IgA anti-H7 inplasma and feces, respectively, in immunized mice at all times evaluated from the 7 thday after the 2 nd dose (p<0.05). We observed specific proliferation only in lymphocytesfrom the S and LN of immunized mice compared to controls (LN MFI CFSE: 39.5±5.5 vs95.3±6.2, p<0.001; S MFI CFSE: 48.6±9.1 vs 95.1±16.8, p<0.05 immunized vscontrols). Also, significant levels of IL-4, IL-17 and IFN-γ were detected in thesesupernatants (p<0.01). When challenged, all immunized mice survived up to 15 dayspost-infection (dpi) (p<0.01), with basal levels of urea (p<0.0001) and slight neutrophilia(p<0.001) compared to controls that died by 8 dpi with increased urea levels andneutrophilia. These results show that H7 is an immunogen capable of eliciting a specifichumoral, Th1/Th2/Th17 cellular and protective response, suggesting its inclusion in apotential human vaccine.