biostudies-literatureTzeng YLNational Institute of Allergy and Infectious DiseasesNIAID NIH HHS1350344https://www.ebi.ac.uk/biostudies/studies/S-EPMC10909805biostudies-literatureUnknown15<h4>Introduction</h4>Outer membrane vesicles (OMVs) of <i>Neisseria meningitidis</i> in the group B-directed vaccine MenB-4C (Bexsero^R) protect against infections with <i>Neisseria gonorrhoeae</i>. The immunological basis for protection remains unclear. <i>N. meningitidis</i> OMV vaccines generate human antibodies to <i>N. meningitidis</i> and <i>N. gonorrhoeae</i> lipooligosaccharide (LOS/endotoxin), but the structural specificity of these LOS antibodies is not defined.<h4>Methods</h4>Ten paired human sera obtained pre- and post-MenB-4C immunization were used in Western blots to probe <i>N. meningitidis</i> and <i>N. gonorrhoeae</i> LOS. Post-MenB-4C sera (7v5, 19v5, and 17v5), representing individual human variability in LOS recognition, were then used to interrogate structurally defined LOSs of <i>N. meningitidis</i> and <i>N. gonorrhoeae</i> strains and mutants and studied in bactericidal assays.<h4>Results and discussion</h4>Post-MenB-4C sera recognized both <i>N. meningitidis</i> and <i>N. gonorrhoeae</i> LOS species, ~10% of total IgG to gonococcal OMV antigens. <i>N. meningitidis</i> and <i>N. gonorrhoeae</i> LOSs were broadly recognized by post-IgG antibodies, but with individual variability for LOS structures. Deep truncation of LOS, specifically a <i>rfa</i>K mutant without <i>α</i>-, <i>β</i>-, or <i>γ</i>-chain glycosylation, eliminated LOS recognition by all post-vaccine sera. Serum 7v5 IgG antibodies recognized the unsialyated L1 <i>α</i>-chain, and a 3-PEA-HepII or 6-PEA-HepII was part of the conformational epitope. Replacing the 3-PEA on HepII with a 3-Glc blocked 7v5 IgG antibody recognition of <i>N. meningitidis</i> and <i>N. gonorrhoeae</i> LOSs. Serum 19v5 recognized lactoneotetrose (LNT) or L1 LOS-expressing <i>N. meningitidis</i> or <i>N. gonorrhoeae</i> with a minimal <i>α</i>-chain structure of Gal-Glc-HepI (L8), a 3-PEA-HepII or 6-PEA-HepII was again part of the conformational epitope and a 3-Glc-HepII blocked 19v5 antibody binding. Serum 17v5 LOS antibodies recognized LNT or L1 <i>α</i>-chains with a minimal HepI structure of three sugars and no requirement for HepII modifications. These LOS antibodies contributed to the serum bactericidal activity against <i>N. gonorrhoeae</i>. The MenB-4C vaccination elicits bactericidal IgG antibodies to <i>N. gonorrhoeae</i> conformational epitopes involving HepI and HepII glycosylated LOS structures shared between <i>N. meningitidis</i> and <i>N. gonorrhoeae.</i> LOS structures should be considered in next-generation gonococcal vaccine design.Frontiers in immunology<i>Neisseria gonorrhoeae</i> lipooligosaccharide glycan epitopes recognized by bactericidal IgG antibodies elicited by the meningococcal group B-directed vaccine, MenB-4C.PMC10909805R01 AI127863R21 AI164733Borrow RStephens DSTzeng YLSannigrahi Sfalse<i>Neisseria gonorrhoeae</i> lipooligosaccharide glycan epitopes recognized by bactericidal IgG antibodies elicited by the meningococcal group B-directed vaccine, MenB-4C.<h4>Introduction</h4>Outer membrane vesicles (OMVs) of <i>Neisseria meningitidis</i> in the group B-directed vaccine MenB-4C (Bexsero^R) protect against infections with <i>Neisseria gonorrhoeae</i>. The immunological basis for protection remains unclear. <i>N. meningitidis</i> OMV vaccines generate human antibodies to <i>N. meningitidis</i> and <i>N. gonorrhoeae</i> lipooligosaccharide (LOS/endotoxin), but the structural specificity of these LOS antibodies is not defined.<h4>Methods</h4>Ten paired human sera obtained pre- and post-MenB-4C immunization were used in Western blots to probe <i>N. meningitidis</i> and <i>N. gonorrhoeae</i> LOS. Post-MenB-4C sera (7v5, 19v5, and 17v5), representing individual human variability in LOS recognition, were then used to interrogate structurally defined LOSs of <i>N. meningitidis</i> and <i>N. gonorrhoeae</i> strains and mutants and studied in bactericidal assays.<h4>Results and discussion</h4>Post-MenB-4C sera recognized both <i>N. meningitidis</i> and <i>N. gonorrhoeae</i> LOS species, ~10% of total IgG to gonococcal OMV antigens. <i>N. meningitidis</i> and <i>N. gonorrhoeae</i> LOSs were broadly recognized by post-IgG antibodies, but with individual variability for LOS structures. Deep truncation of LOS, specifically a <i>rfa</i>K mutant without <i>α</i>-, <i>β</i>-, or <i>γ</i>-chain glycosylation, eliminated LOS recognition by all post-vaccine sera. Serum 7v5 IgG antibodies recognized the unsialyated L1 <i>α</i>-chain, and a 3-PEA-HepII or 6-PEA-HepII was part of the conformational epitope. Replacing the 3-PEA on HepII with a 3-Glc blocked 7v5 IgG antibody recognition of <i>N. meningitidis</i> and <i>N. gonorrhoeae</i> LOSs. Serum 19v5 recognized lactoneotetrose (LNT) or L1 LOS-expressing <i>N. meningitidis</i> or <i>N. gonorrhoeae</i> with a minimal <i>α</i>-chain structure of Gal-Glc-HepI (L8), a 3-PEA-HepII or 6-PEA-HepII was again part of the conformational epitope and a 3-Glc-HepII blocked 19v5 antibody binding. Serum 17v5 LOS antibodies recognized LNT or L1 <i>α</i>-chains with a minimal HepI structure of three sugars and no requirement for HepII modifications. These LOS antibodies contributed to the serum bactericidal activity against <i>N. gonorrhoeae</i>. The MenB-4C vaccination elicits bactericidal IgG antibodies to <i>N. gonorrhoeae</i> conformational epitopes involving HepI and HepII glycosylated LOS structures shared between <i>N. meningitidis</i> and <i>N. gonorrhoeae.</i> LOS structures should be considered in next-generation gonococcal vaccine design.2024-01-01T00:00:00Z20242026-06-16T04:54:03.769Z2026-06-16T03:07:31.567ZS-EPMC109098053844073110.3389/fimmu.2024.1350344