A candidate antibody drug for malaria prevention has been developed based on B cell repertoires from 45 RTS,S/AS01 vaccinees. Researchers generated over 28,000 antibody sequences and tested 481 for binding activity and 125 for antimalarial activity in vivo. They identified two antibodies, AB-000224 and AB-007088, for clinical development. These antibodies were engineered to improve manufacturing and stability, aligning with WHO guidelines. The optimized antibody, MAM01, showed comparable in vivo efficacy to AB-000317, which was previously not advanced due to suboptimal expression and cross-reactivity. The study highlights the importance of immunodominant antibody responses and the need for complementary strategies to malaria prevention. The findings suggest that antibodies targeting the circumsporozoite protein (CSP) may have limited protective efficacy, and that more effective antibodies may require broader epitope recognition. The developed antibody, MAM01, is a promising candidate for use in pediatric populations in low- and middle-income countries.A candidate antibody drug for malaria prevention has been developed based on B cell repertoires from 45 RTS,S/AS01 vaccinees. Researchers generated over 28,000 antibody sequences and tested 481 for binding activity and 125 for antimalarial activity in vivo. They identified two antibodies, AB-000224 and AB-007088, for clinical development. These antibodies were engineered to improve manufacturing and stability, aligning with WHO guidelines. The optimized antibody, MAM01, showed comparable in vivo efficacy to AB-000317, which was previously not advanced due to suboptimal expression and cross-reactivity. The study highlights the importance of immunodominant antibody responses and the need for complementary strategies to malaria prevention. The findings suggest that antibodies targeting the circumsporozoite protein (CSP) may have limited protective efficacy, and that more effective antibodies may require broader epitope recognition. The developed antibody, MAM01, is a promising candidate for use in pediatric populations in low- and middle-income countries.