{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T03:36:06Z","timestamp":1768966566615,"version":"3.49.0"},"reference-count":75,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,9,22]],"date-time":"2022-09-22T00:00:00Z","timestamp":1663804800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p><jats:italic>Plasmodium falciparum<\/jats:italic> Cysteine-Rich Protective Antigen (CyRPA) is an essential, highly conserved merozoite antigen that forms an important multi-protein complex (RH5\/Ripr\/CyRPA) necessary for erythrocyte invasion. CyRPA is a promising blood-stage vaccine target that has been shown to elicit potent strain-transcending parasite neutralizing antibodies. Recently, we demonstrated that naturally acquired immune anti-CyRPA antibodies are invasion-inhibitory and therefore a correlate of protection against malaria. Here, we describe a process for the large-scale production of tag-free CyRPA vaccine in <jats:italic>E. coli<\/jats:italic> and demonstrate its parasite neutralizing efficacy with commonly used adjuvants. CyRPA was purified from inclusion bodies using a one-step purification method with high purity (&amp;gt;90%). Biochemical and biophysical characterization showed that the purified tag-free CyRPA interacted with RH5, readily detected by a conformation-specific CyRPA monoclonal antibody and recognized by sera from malaria infected individuals thus indicating that the recombinant antigen was correctly folded and retained its native conformation. Tag-free CyRPA formulated with Freund\u2019s adjuvant elicited highly potent parasite neutralizing antibodies achieving inhibition of &amp;gt;90% across diverse parasite strains. Importantly, we identified tag-free CyRPA\/Alhydrogel formulation as most effective in inducing a highly immunogenic antibody response that exhibited efficacious, cross-strain <jats:italic>in vitro<\/jats:italic> parasite neutralization achieving ~80% at 10 mg\/ml. Further, CyRPA\/Alhydrogel vaccine induced anti-parasite cytokine response in mice. In summary, our study provides a simple, scalable, cost-effective process for the production of tag-free CyRPA that in combination with human-compatible adjuvant induces efficacious humoral and cell-mediated immune response.<\/jats:p>","DOI":"10.3389\/fimmu.2022.1005332","type":"journal-article","created":{"date-parts":[[2022,9,22]],"date-time":"2022-09-22T10:50:26Z","timestamp":1663843826000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Process development and preclinical evaluation of a major Plasmodium falciparum blood stage vaccine candidate, Cysteine-Rich Protective Antigen (CyRPA)"],"prefix":"10.3389","volume":"13","author":[{"given":"Anjali","family":"Somanathan","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Syed 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