A potent adjuvant effect of CD40 antibody attached to antigen

There is great potential for novel vaccines based on recombinant proteins and synthetic peptides. Unfortunately these antigens often lack the immunogenicity of whole, killed pathogens used in traditional vaccines. Thus there is strong interest in the identification of immunological adjuvants with low reactogenicity, but high potency, to enhance immune responses and realize the potential of these new vaccine strategies. CD40 antibodies have been shown to have adjuvant effects when administered at very high doses. These large doses are impractical and induce a cascade of cytokine release giving rise to septic shock-like symptoms, as well as splenomegaly and polyclonal antibody production. We show here that a very small amount of CD40 antibody can exhibit potent adjuvant effects when attached to soluble antigen. The lack of detectable systemic effects indicates that this method may be a powerful and practical means of enhancing the efficacy of recombinant vaccines

Fcγ receptors are crucial for the expression of acquired resistance to virulent Salmonella enterica serovar Typhimurium in vivo but are not required for the induction of humoral or T-cell-mediated immunity

Antibodies play an important role in immunity to Salmonella enterica. Here we evaluated the requirement for Fcγ receptors in host resistance to S. enterica using an in vivo model of systemic infection. We show that mice lacking FcγRI, II and III can control and clear a primary infection with S. enterica micro-organisms of low virulence, but are impaired in the expression of vaccine-induced acquired immunity to oral challenge with virulent bacteria. We also show that, in vivo, FcγRI, II, III−/− mice were able to mount efficient T-helper 1 type T-cell responses and antibody responses specific for S. enterica. The work indicates that targeting S. enterica to FcγR is needed for the expression of vaccine-induced acquired immunity, but is not essential for the engenderment of T- and B-cell immunity to the bacterium in vivo