Immunomodulatory effects of oligosaccharide preparations that resemble chemical and functional aspects of human milk oligosaccharides (HMOS) were studied for the development of new concepts in infant nutrition. A dose range of 1-5% (w/w) dietary pectin-derived acidic oligosaccharides (AOS) was tested in a murine influenza vaccination model. In addition, combinations of AOS and a 9:1 mixture of galacto-oligosaccharides and long-chain fructo-oligosaccharides (GOS/FOS) were tested at a fixed total dietary dose of 2% (w/w). It was found that AOS significantly enhanced vaccine-specific delayed-type hypersensitivity (DTH) responses in a dose-dependent manner. This was accompanied by a reduction in T-helper2 (Th2) cytokine production by splenocytes in vitro. Overall, this indicates that the systemic immune response to the vaccine was Th1-skewed by the dietary intervention. Combinations of GOS/FOS and AOS were more effective in enhancing DTH responses than either of the oligosaccharides alone, suggesting interaction effects between these agents. Similar to effects in infants, supplementation of the murine diets with GOS/FOS and combinations of GOS/FOS and AOS for 6-wk enhanced the proportion of fecal bifidobacteria and lactobacilli, but AOS alone did not. In conclusion, these data indicate that GOS/FOS and AOS enhance systemic Th1-dependent immune responses in a murine vaccination model. As Th1-responses are weak in early life in humans, this might suggest that application of these oligosaccharides in infant formulas will be beneficial for the development of the infant's immune system.