Limitations of in vivo IL-12 supplementation strategies to induce Th1 early life responses to model viral and bacterial vaccine antigens

The limited induction of Th1 and cytotoxic immune responses is regarded as the main reason for the increased susceptibility to intracellular microorga nisms in early life. Recently, in vitro IL-12 supplementation was shown to enhance the limited IFN-gamma release of measles-specific infant T cells. U sing a series of IL-12 delivery systems, we show here that in vivo IL-12 su pplementation may enhance early life murine Th1 responses to two model vacc ine antigens, measles virus hemagglutinin and tetanus toxin peptide. Howeve r, this required multiple repeat injections of recombinant rIL-12, which we re poorly tolerated in young mice. Local IL-12 delivery by an IL-12 express ing canarypox vector proved safe but failed to modulate vaccine responses. An IL-12 DNA plasmid or a CD40L DNA plasmid efficiently enhanced neonatal T h1 responses to measles hemagglutinin DNA vaccine. However, both plasmids o nly enhanced Th1 responses to DNA and not to peptide, protein, or live vira l vaccines. Thus, inducing adult-like Th1 responses may be achieved in vivo by inducing (CD40L) or substituting for (IL-12 supplementation) optimal ac tivation of neonatal APC. However, these immunomodulatory effects appear li mited to certain antigen-presentation approaches and may not be broadly app licable to vaccines. (C) 2000 Academic Press.