Influence of maternal antibodies on vaccine responses: inhibition of antibody but not T cell responses allows successful early prime-boost strategiesin mice

The transfer of maternal antibodies to the offspring and their inhibitory e ffects on active infant immunization is an important factor hampering the u se of certain vaccines, such as measles or respiratory syncytial virus vacc ine, in early infancy. The resulting delay in protection by conventional or novel vaccines may have significant public health consequences. To define immunization approaches which may circumvent this phenomenon, experiments w ere set up to further elucidate its immunological bases. The influence of m aternal antibodies on antibody and T cell responses to measles hemagglutini n (MV-HA) were analyzed following MV-HA immunization of pups born to immune or control BALB/c mothers using four different antigen delivery systems: l ive or inactivated conventional measles vaccine, a live recombinant canaryp ox vector and a DNA vaccine. High levels (> 5 log10) of maternal anti-HA an tibodies totally inhibited antibody responses to each of the Vaccine constr ucts, whereas normal antibody responses were elicited in presence of lower titers of maternal antibodies. However, even high titers of maternal antibo dies affected neither the induction of vaccine-specific Th1/Th2 responses, as assessed by proliferation and levels of IFN-gamma and IL-5 production, n or CTL responses in infant mice. On the basis of these unaltered T cell res ponses, Very early priming and boosting (at 1 and 3 weeks of age, respectiv ely) with live measles vaccine allowed to circumvent maternal antibody inhi bition of antibody responses in pups of immune mothers. This was confirmed in another immunization model (tetanus toxoid). It suggests that effective vaccine responses may be obtained earlier in presence of maternal antibodie s through the use of appropriate immunization strategies using conventional or novel vaccines for early priming.