Enhancement of T cell-independent immune responses in vivo by CD40 antibodies

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Abstract
In this report we describe a potentially powerful method for vaccinating infants against encapsulated bacterial pathogens such as Haemophilus influenzae, Streptococcus pneumoniae and Neisseria meningitidis. High levels of antibody directed against the polysaccharides of the bacterial capsule are normally protective. Unfortunately, the capsular polysaccharides are T cell-independent antigens (TI); lacking T-cell help, they induce only weak, predominantly IgM antibody responses, with infants responding especially poorly. T-cell help, given to B cells during responses to protein antigens, causes stronger antibody responses and isotype switching to the IgG isotypes. T-cell help is mainly mediated through ligation of the B-cell surface antigen, CD40, by its cognate T-cell ligand, CD154. Here we show that administering anti-CD40 monoclonal antibody to mice, along with pneumococcal polysaccharide, provides a substitute for T-cell help and results in the generation of strong, isotype-switched antibody responses, which are protective. The work points the way toward a possible effective and inexpensive means of protecting susceptible groups against important bacterial pathogens.