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Circumsporozoite protein (CSP), the most abundant sporozoite stage antigen, is a prime vaccine candidate. Inhibitory monoclonal antibodies (mAbs) against CSP map to either a short junctional sequence or the central (NPNA)\n                    <jats:sub>n<\/jats:sub>\n                    repeat region. We compared in vitro and in vivo activities of six CSP-specific mAbs derived from human recipients of a recombinant CSP vaccine RTS,S\/AS01 (mAbs 317 and 311); an irradiated whole sporozoite vaccine PfSPZ (mAbs CIS43 and MGG4); or individuals exposed to malaria (mAbs 580 and 663). RTS,S mAb 317 that specifically binds the (NPNA)\n                    <jats:sub>n<\/jats:sub>\n                    epitope, had the highest affinity and it elicited the best sterile protection in mice. The most potent inhibitor of sporozoite invasion in vitro was mAb CIS43 which shows dual-specific binding to the junctional sequence and (NPNA)\n                    <jats:sub>n<\/jats:sub>\n                    . In vivo mouse protection was associated with\u00a0the\u00a0mAb reactivity to the NANPx6 peptide, the\u00a0in vitro inhibition of sporozoite invasion activity,\u00a0and kinetic parameters measured\u00a0using intact mAbs or their Fab fragments. Buried surface area between mAb and its target epitope was\u00a0also associated with in vivo protection. Association and disconnects between in vitro and in vivo readouts has important implications for the design and down-selection of the next generation of CSP based interventions.\n                  <\/jats:p>","DOI":"10.1038\/s41598-021-84622-x","type":"journal-article","created":{"date-parts":[[2021,3,5]],"date-time":"2021-03-05T06:03:22Z","timestamp":1614924202000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["In vitro and in vivo inhibition of malaria parasite infection by monoclonal antibodies against Plasmodium falciparum circumsporozoite protein (CSP)"],"prefix":"10.1038","volume":"11","author":[{"given":"Merricka C.","family":"Livingstone","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexis A.","family":"Bitzer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alish","family":"Giri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajeshwer S.","family":"Sankhala","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Misook","family":"Choe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyan","family":"Zou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. 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