CD40 antibody as a potent immunological adjuvant: CD40 antibody provides the CD40 signal to B cells, but does not substitute for T cell help in responses to TD antigens

Abstract

Agonistic antibodies against CD40 have great potential as immunological adjuvants. We have shown that CD40mAbs induce strong antibody responses against conjugated antigen, and that this enhancement of responses extends to any sequence physically associated to the CD40 binding moiety, including the antibody's own Fc region. Thus, the CD40mAb acts as a model immunogen, containing both antigenic (i.e. Fc portion) and CD40 binding motifs (i.e. CD40 binding moiety). Using this system we examine here whether CD40mAb is able to directly mimic T cell help to B cells. CD40mAbs have no adjuvant effect in CD4 depleted mice, and thus, do not mimic T cell help. Simultaneous administration of recombinant IL-4 was unable to restore the adjuvant action of anti-CD40 in T cell depleted mice. However, CD40mAbs are effective adjuvants in CD154−/− mice, indicating that the antibodies are able to provide the CD40 stimulus to B cells which is naturally lacking in these mice. Identification of the additional stimuli required to fully mimic T cell help may be advantageous in vaccination of immunosuppressed patients.