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Recently, two highly protective human mAbs 224 (IGHV3\u201049\/IGLV1\u201040) and 7088 (IGHV3\u201033\/IGKV1\u20105), encoded by distinct germline genes, were re\u2010engineered and renamed MAM01 and MS\u20101805, respectively, to extend serum half\u2010life and enable low\u2010cost, large\u2010scale manufacturing in alignment with WHO guidelines. MAM01 completed Phase I and IIb clinical trials (safety\/PK\/challenge) in US healthy naive adults and is now in Phase I trials (age\u2010de\u2010escalation studies) in Uganda. Here, we determined crystal structures of the antigen\u2010binding fragments (Fabs) of engineered MAM01, MS\u20101805, and 7088 in complex with different regions of the\n                    <jats:italic>Plasmodium falciparum<\/jats:italic>\n                    circumsporozoite protein (PfCSP), including junctional, minor, and major repeat regions. Notably, Fab 7088 features an extended CDRL3 comprising 10 amino acids (CDRL3:10) instead of the canonical 8 amino acid CDRL3 (CDRL3:8) typically observed in V\n                    <jats:sub>H<\/jats:sub>\n                    3\u201033\/V\n                    <jats:sub>K<\/jats:sub>\n                    1\u20105\u2010encoded mAbs, indicating unique folding within its germline context. In addition, cryo\u2010EM structures of Fabs 7088 and MS\u20101805, in complex with recombinant shortened CSP (rsCSP), revealed a regular spiral configuration stabilized by homotypic Fab\u2010Fab interactions, whereas 224 and MAM01 did not form such assemblies. Structural comparisons demonstrated that engineered antibodies retained key molecular and hydrogen\u2010bond interactions without significant conformational changes, thereby maintaining antigen recognition and preserving binding affinity. These findings demonstrate that targeted framework engineering can enhance therapeutic potential while preserving structural integrity and function, providing insights for next\u2010generation antibody\u2010based interventions against malaria.\n                  <\/jats:p>","DOI":"10.1002\/pro.70738","type":"journal-article","created":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T12:32:04Z","timestamp":1786019524000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Engineered antibodies preserve structural and functional recognition of\n                    <i>Plasmodium falciparum<\/i>\n                    circumsporozoite protein"],"prefix":"10.1002","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8700-4562","authenticated-orcid":false,"given":"Monika","family":"Jain","sequence":"first","affiliation":[{"name":"Department of Integrative Structural and Computational Biology The Scripps Research Institute  La Jolla California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8549-9602","authenticated-orcid":false,"given":"Sashank","family":"Agrawal","sequence":"additional","affiliation":[{"name":"Department of Integrative Structural and Computational Biology The Scripps Research Institute  La Jolla California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabien","family":"Cannac","sequence":"additional","affiliation":[{"name":"Department of Integrative Structural and Computational Biology The Scripps Research Institute  La Jolla California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gonzalo E.","family":"Gonz\u00e1lez\u2010P\u00e1ez","sequence":"additional","affiliation":[{"name":"Department of Integrative Structural and Computational Biology The Scripps Research Institute  La Jolla California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen\u2010Hsin","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Integrative Structural and Computational Biology The Scripps Research Institute  La Jolla California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Re'em","family":"Moskovitz","sequence":"additional","affiliation":[{"name":"Department of Integrative Structural and Computational Biology The Scripps Research Institute  La Jolla California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7821-2682","authenticated-orcid":false,"given":"Randal R.","family":"Ketchem","sequence":"additional","affiliation":[{"name":"Just\u2010Evotec Biologics  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine L.","family":"Williams","sequence":"additional","affiliation":[{"name":"Atreca, Inc.  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