We have shown that it is possible to interrogate the memory B-cell repertoire of malaria-immune donors to estimate frequencies of P. falciparum-specific B cells, and to isolate specific monoclonal antibodies with specificity for the VSA repeatedly implicated as the main targets of acquired protective immunity to malaria. We have used this approach to demonstrate that PAM can result in acquisition of high frequencies of B cells producing IgG with specificity for VSA PAM, and in particular VAR2CSA, strengthening previous evidence that these antigen specificities are critically important in acquired protective immunity to PAM. We furthermore show that VSAPAM-specific memory B cells acquired in response to PAM primarily target polymorphic, conformationdependent epitopes that are reproduced by Baculovirusproduced recombinant antigen constructs. Our data thus underscore the importance of VAR2CSA in acquired B. Pre-selection non-PAM VSA-type recognition pattern of EJ27 by IgG in plasma from P. falciparum-exposed men and women and in plasma from non-exposed adults. C. Reactivity of PAM1.4 antibody (heavy line) and negative control antibody (thin line) with the surface of erythrocytes infected by the EJ27 after a single round of selection for reactivity with PAM1.4. D. Post-selection VSAPAM-type recognition pattern of EJ27 by IgG in plasma from P. falciparum-exposed men and women and in plasma from non-exposed adults.