Ligation of CD11c during vaccination promotes germinal centre induction and robust humoral responses without adjuvant.
Authors
White, Ann LTutt, Alison L
James, Sonya
Wilkinson, Kevin A
Castro, Fernanda V
Dixon, Sandra V
Hitchcock, Jessica
Khan, Mahmood
Al-Shamkhani, Aymen
Cunningham, Adam F
Glennie, Martin J
Affiliation
Tenovus Research Laboratory, Cancer Sciences Division, Southampton University School of Medicine, General Hospital, Southampton, UK.Issue Date
2010-09
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In this study, we investigated the mouse dendritic cell (DC) receptor, complement receptor 4 (CR4; CD11c/CD18), as an immunotarget for triggering humoral immunity. Comparison of antibody titres generated against a panel of 13 anti-antigen-presenting cell receptor monoclonal antibodies, with or without conjugated ovalbumin (OVA), revealed uniquely rapid and robust responses following CR4 targeting, with antibody titres approaching 1 : 100 000 7 days after a single dose of antigen. Furthermore, using just 100 ng OVA conjugated to anti-CD11c Fab', we generated anti-OVA titres greater than those produced by a 100-fold higher dose of OVA in complete Freund's adjuvant at day 28. These anti-OVA antibody titres were sustained and could be boosted further with targeted OVA on day 21. Investigations to explain this vaccine potency showed that, in addition to targeting splenic DC, anti-CDl1c antibodies delivered a powerful adjuvant effect and could boost humoral immunity against OVA even when the OVA was targeted to other molecules on DC, such as major histocompatibility complex class II, CD11a and CD11b. However, interestingly, this adjuvant effect was lost if OVA was targeted to other cells such as B cells via CD21 or CD19. The adjuvant effect was mediated through a marked enhancement of both germinal centre and extrafollicular plasma cell formation in responding spleens. These results demonstrate that anti-CD11c monoclonal antibody can both target antigen and act as a powerful adjuvant for rapid and sustained antibody responses. They also point to an interesting role for CR4 on DC in triggering B cells during humoral immunity.Citation
Ligation of CD11c during vaccination promotes germinal centre induction and robust humoral responses without adjuvant. 2010, 131 (1):141-51 ImmunologyJournal
ImmunologyDOI
10.1111/j.1365-2567.2010.03285.xPubMed ID
20465572Type
ArticleLanguage
enISSN
1365-2567ae974a485f413a2113503eed53cd6c53
10.1111/j.1365-2567.2010.03285.x
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