%0 Journal Article
%T A Fluorinated Sialic Acid Vaccine Lead Against Meningitis B and C.
%A Jordan C
%A Siebold K
%A Priegue P
%A Seeberger PH
%A Gilmour R
%J J Am Chem Soc
%V 146
%N 22
%D 2024 Jun 5
%M 38768956
%F 16.383
%R 10.1021/jacs.4c03179
%X Inspired by the specificity of α-(2,9)-sialyl epitopes in bacterial capsular polysaccharides (CPS), a doubly fluorinated disaccharide has been validated as a vaccine lead against Neisseria meningitidis serogroups C and/or B. Emulating the importance of fluorine in drug discovery, this molecular editing approach serves a multitude of purposes, which range from controlling α-selective chemical sialylation to mitigating competing elimination. Conjugation of the disialoside with two carrier proteins (CRM197 and PorA) enabled a semisynthetic vaccine to be generated; this was then investigated in six groups of six mice. The individual levels of antibodies formed were compared and classified as highly glycan-specific and protective. All glycoconjugates induced a stable and long-term IgG response and binding to the native CPS epitope was achieved. The generated antibodies were protective against MenC and/or MenB; this was validated in vitro by SBA and OPKA assays. By merging the fluorinated glycan epitope of MenC with an outer cell membrane protein of MenB, a bivalent vaccine against both serogroups was created. It is envisaged that validation of this synthetic, fluorinated disialoside bioisostere as a potent antigen will open new therapeutic avenues.