Ligation of CD11c during vaccination promotes germinal centre induction and robust humoral responses without adjuvant.
AuthorsWhite, Ann L
Tutt, Alison L
Wilkinson, Kevin A
Castro, Fernanda V
Dixon, Sandra V
Cunningham, Adam F
Glennie, Martin J
AffiliationTenovus Research Laboratory, Cancer Sciences Division, Southampton University School of Medicine, General Hospital, Southampton, UK.
MetadataShow full item record
AbstractIn 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.
CitationLigation of CD11c during vaccination promotes germinal centre induction and robust humoral responses without adjuvant. 2010, 131 (1):141-51 Immunology
- Efficient targeting of protein antigen to the dendritic cell receptor DEC-205 in the steady state leads to antigen presentation on major histocompatibility complex class I products and peripheral CD8+ T cell tolerance.
- Authors: Bonifaz L, Bonnyay D, Mahnke K, Rivera M, Nussenzweig MC, Steinman RM
- Issue date: 2002 Dec 16
- CD11c provides an effective immunotarget for the generation of both CD4 and CD8 T cell responses.
- Authors: Castro FV, Tutt AL, White AL, Teeling JL, James S, French RR, Glennie MJ
- Issue date: 2008 Aug
- Immunization with functionalized carbon nanotubes enhances the antibody response against mode antigen ovalbumin.
- Authors: Zhu X, Sun J, Zhang Y, Sun X
- Issue date: 2016 Oct
- Antigen targeting to dendritic cells elicits long-lived T cell help for antibody responses.
- Authors: Boscardin SB, Hafalla JC, Masilamani RF, Kamphorst AO, Zebroski HA, Rai U, Morrot A, Zavala F, Steinman RM, Nussenzweig RS, Nussenzweig MC
- Issue date: 2006 Mar 20
- Oral antigen exposure in extreme early life in lambs influences the magnitude of the immune response which can be generated in later life.
- Authors: Buchanan RM, Mertins S, Wilson HL
- Issue date: 2013 Aug 12