Presence of maternally-derived antibodies at time of immunization is known to often interfere with active infant immunization, although with variable degrees of clinical significance. In order to progressively decipher the rules that form the basis for these inhibitory effects on infant vaccine responses, two antigens (measles, tetanus) and various antigen presentation systems were evaluated in murine early life immunization models either in absence or presence of maternal antibodies. Both conventional (proteins, conjugate vaccines) and new (live viral vectors, DNA plasmids) antigen presentation systems were found to be similarly susceptible to the inhibitory influence of maternal antibodies. Factors emerging as crucial determinants of maternal antibody-mediated effects on responses to both live and non-live vaccines include (i) the level of maternal antibodies present at immunization, (ii) the use of distinct vaccines in mothers and pups and (iii) their distinct influence on B cell and T cell vaccine responses.