CpG oligodeoxynucleotides can circumvent the th2 polarization of neonatal responses to vaccines but may pail to fully redirect Th2 responses established by neonatal priming

Neonatal murine responses to a panel of conventional vaccines differ qualit atively from adult responses by a particular polarization toward a Th2 patt ern and a frequent limitation of the Th1 and CTL responses required for pro tection against intracellular microorganisms. Tn contrast, DNA vaccines ind uce adult-like Th1/CTL neonatal responses against the same vaccine Ags. In this report, we show that this can be related to their content in ummethyla ted CpG moths, Oligodeoxynucleotides (ODN) containing CPG motifs activate n eonatal APCs to produce IL-12 in vitro and induce adult-like Th1 responses to tetanus toroid and measles Ags in vivo, with production of IgG2a-specifi c Abs and adult-like secretion of IFN-gamma and IL-5 by Ag-specific T cells , However, in spite of their capacity to trigger neonatal B cell proliferat ion in vitro, CpG-ODN only partially enhanced early life Ab responses. Fina lly, using Th1-driving CpG-ODN with the boosting dose of a protein vaccine was sufficient to redirect adult but not neonatally primed Th2 responses. T hese observations could be important for the development of novel vaccines that will have to be effective early in life.