Antibody gene features associated with binding and functional activity in vaccine-derived human mAbs targeting malaria parasites

• Published in: bioRxiv
• Main Authors: Coelho, Camila H, Marquez, Susanna, Tentokam, Bergeline C Nguemwo, Berhe, Anne D, Miura, Kazutoyo, Long, Carole A, Sagara, Issaka, Healy, Sara, Kleinstein, Steven H, Duffy, Patrick E
• Format: Journal Article
• Language: English
• Published: United States 03.08.2023
• ISSN: 2692-8205; 2692-8205
• DOI: 10.1101/2023.08.01.551554

Adjuvants have been essential to malaria vaccine development, but their impact on the vaccine-induced antibody repertoire is poorly understood. Here, we used cDNA sequences from antigen-specific single memory B cells to express 132 recombinant human anti-Pfs230 monoclonal antibodies (mAbs). Alhydrogel -induced mAbs demonstrated higher binding to Pfs230D1, although functional activity was similar between adjuvants. All Alhydrogel mAbs using IGHV1-69 gene bound to recombinant Pfs230D1, but none blocked parasite transmission to mosquitoes; similarly, no AS01 mAb using IGHV1-69 blocked transmission. Functional mAbs from both Alhydrogel and AS01 vaccines used IGHV3-21 and IGHV3-30 genes. Antibodies with the longest CDR3 sequences were associated with binding but not functional activity. This study assesses adjuvant effects on antibody clonotype diversity during malaria vaccination.