Since pediatric SW155246 populations in endemic areas constitute the main target group for a malaria vaccine, it is important to investigate immune responses induced by RTS,S vaccines in this age group and also provide a better understanding of immune mechanisms which mediate protection. In this study we have investigated the impact of RTS,S vaccination on the induction of CS-specific antibodies, circulating memory B cells and CD4 + T cell responses in children aged 18 months to 4 years, vaccinated with AS01E or AS02D based formulations. While the rationale for investigating CD4 + T cell responses is based on their potential role in protection against infection in adults, memory B cell responses and their relation to circulating antibody titers have not been evaluated with the RTS,S candidate vaccine. This study investigated the adaptive B and T cell immune responses induced by the RTS,S antigen formulated with two different adjuvant systems in 18 month to 4 year old children living in a malaria endemic region. This study demonstrates the induction one month after doses 2 and 3 as well as persistence at month 12 after last immunization of CS- specific circulating memory B cell and CS-specific BC-1258 antibodies in RTS,S/AS01E and RTS,S/AS02D vaccinated children. Similar to the association between the levels of antibodies to serogroup C meningococcal polysaccharide and the levels of circulating memory B cells in infants vaccinated with the MenC glycoconjugate vaccine, these data suggest the replenishment of the plasma cell pool on a regular basis through differentiation of CS specific memory B cells. An alternative model proposes that long lived plasma cells would be solely responsible for the maintenance of serum antibodies titers. However, the short half-life of long-lived plasma cells described in several animal and human studies make a scenario in which long-lived plasma cells sustain antibody production without continuous replenishment from memory B cells unlikely. After two vaccine administrations, a higher frequency of CSspecific memory B cells was induced with the RTS,S/AS01E than with RTS,S/AS02D.