{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T08:49:07Z","timestamp":1791276547302,"version":"4.1.0"},"reference-count":66,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2014,8,1]],"date-time":"2014-08-01T00:00:00Z","timestamp":1406851200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,8,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Almost all invasive Neisseria meningitidis isolates express capsular polysaccharide. Ab is required for complement-dependent killing of meningococci. Although alternative pathway evasion has received considerable attention, little is known about classical pathway (CP) inhibition by meningococci, which forms the basis of this study. We engineered capsulated and unencapsulated isogenic mutant strains of groups A, B, C, W, and Y meningococci to express similar amounts of the same factor H\u2013binding protein (fHbp; a key component of group B meningococcal vaccines) molecule. Despite similar anti-fHbp mAb binding, significantly less C4b was deposited on all five encapsulated mutants compared with their unencapsulated counterparts (p &amp;lt; 0.01) when purified C1 and C4 were used to deposit C4b. Reduced C4b deposition was the result of capsule-mediated inhibition of C1q engagement by Ab. C4b deposition correlated linearly with C1q engagement by anti-fHbp. Whereas B, C, W, and Y capsules limited CP-mediated killing by anti-fHbp, the unencapsulated group A mutant paradoxically was more resistant than its encapsulated counterpart. Strains varied considerably in their susceptibility to anti-fHbp and complement despite similar Ab binding, which may have implications for the activity of fHbp-based vaccines. Capsule also limited C4b deposition by anti\u2013porin A mAbs. Capsule expression decreased binding of an anti-lipooligosaccharide IgM mAb (\u223c1.2- to 2-fold reduction in fluorescence). Akin to observations with IgG, capsule also decreased IgM-mediated C4b deposition when IgM binding to the mutant strain pairs was normalized. In conclusion, we show that capsular polysaccharide, a critical meningococcal virulence factor, inhibits the CP of complement.<\/jats:p>","DOI":"10.4049\/jimmunol.1303177","type":"journal-article","created":{"date-parts":[[2014,7,12]],"date-time":"2014-07-12T03:00:11Z","timestamp":1405134011000},"page":"1855-1863","source":"Crossref","is-referenced-by-count":35,"title":["Inhibition of the Classical Pathway of Complement by Meningococcal Capsular Polysaccharides"],"prefix":"10.1093","volume":"193","author":[{"given":"Sarika","family":"Agarwal","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases and Immunology, University of Massachusetts Medical School , Worcester MA 01605"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shreekant","family":"Vasudhev","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Immunology, University of Massachusetts Medical School , Worcester MA 01605"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosane B","family":"DeOliveira","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Immunology, University of Massachusetts Medical School , Worcester MA 01605"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjay","family":"Ram","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Immunology, University of Massachusetts Medical School , Worcester MA 01605"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2014,8,15]]},"reference":[{"key":"2025030707280249300_r1","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1084\/jem.17.5.553","article-title":"The results of the serum treatment in thirteen hundred cases of epidemic meningitis","volume":"17","author":"Flexner","year":"1913","journal-title":"J. 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