R21/Matrix-M elicits polyclonal IgG plasma antibodies cross-reactive with the N-terminal JR of CSP despite its absence in the vaccine construct. NANP₆ affinity chromatography depletes the plasma of JR-specific antibodies. (A) The schematic (A) illustrates the truncated CSP used in R21 (and RTS,S) vaccine constructs and the corresponding lack of the N-terminal JR. (B) Heat maps illustrate the signal loss (OD) in four VAC065 volunteers when measured by indirect ELISA using NANP₆ peptide or JR peptide (JR: KQPADGNPDPNANPNVDPN) after affinity chromatography and the depletion of NANP₆-reactive IgG from day 84 plasma at pre-challenge (C₋₁) and post-challenge (C₊₃₅) time points. (C) The bar graph illustrates Ig-Seq analysis of pre-challenge IgG in one volunteer (MA-1010).