{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T11:43:31Z","timestamp":1785757411443,"version":"3.56.0"},"reference-count":66,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2023,11,30]],"date-time":"2023-11-30T00:00:00Z","timestamp":1701302400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institutes of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R43AI091089"],"award-info":[{"award-number":["R43AI091089"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>We previously reported a protective antibody response in mice immunized with synthetic microparticle vaccines made using layer-by-layer fabrication (LbL-MP) and containing the conserved T1BT* epitopes from the P. falciparum circumsporozoite protein. To further optimize the vaccine candidate, a benchtop tangential flow filtration method (LbL-by-TFF) was developed and utilized to produce vaccine candidates that differed in the status of base layer crosslinking, inclusion of a TLR2 ligand in the antigenic peptide, and substitution of serine or alanine for an unpaired cysteine residue in the T* epitope. Studies in mice revealed consistent superiority of the Pam3Cys-modified candidates and a modest benefit of base layer crosslinking, as evidenced by higher and more persistent antibody titers (up to 18 months post-immunization), a qualitative improvement of T-cell responses toward a Th1 phenotype, and greater protection from live parasite challenges compared to the unmodified prototype candidate. Immunogenicity was also tested in a non-human primate model, the rhesus macaque. Base layer-crosslinked LbL-MP loaded with T1BT* peptide with or without covalently linked Pam3Cys elicited T1B-specific antibody responses and T1BT*-specific T-cell responses dominated by IFN\u03b3 secretion with lower levels of IL-5 secretion. The Pam3Cys-modified construct was more potent, generating antibody responses that neutralized wild-type P. falciparum in an in vitro hepatocyte invasion assay. IgG purified from individual macaques immunized with Pam3Cys.T1BT* LbL-MP protected na\u00efve mice from challenges with transgenic P. berghei sporozoites that expressed the full-length PfCS protein, with 50\u201388% of passively immunized mice parasite-free for \u226515 days. Substitution of serine for an unpaired cysteine in the T* region of the T1BT* subunit did not adversely impact immune potency in the mouse while simplifying the manufacture of the antigenic peptide. In a Good Laboratory Practices compliant rabbit toxicology study, the base layer-crosslinked, Pam3Cys-modified, serine-substituted candidate was shown to be safe and immunogenic, eliciting parasite-neutralizing antibody responses and establishing the dose\/route\/regimen for a clinical evaluation of this novel synthetic microparticle pre-erythrocytic malaria vaccine candidate.<\/jats:p>","DOI":"10.3390\/vaccines11121789","type":"journal-article","created":{"date-parts":[[2023,11,30]],"date-time":"2023-11-30T09:37:54Z","timestamp":1701337074000},"page":"1789","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Immunogenicity, Efficacy, and Safety of a Novel Synthetic Microparticle Pre-Erythrocytic Malaria Vaccine in Multiple Host Species"],"prefix":"10.3390","volume":"11","author":[{"given":"Thomas","family":"Powell","sequence":"first","affiliation":[{"name":"Artificial Cell Technologies, Inc., 5 Science Park, Suite 13, New Haven, CT 06511, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Tang","sequence":"additional","affiliation":[{"name":"Artificial Cell Technologies, Inc., 5 Science Park, Suite 13, New Haven, CT 06511, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Mitchell","sequence":"additional","affiliation":[{"name":"Department of Microbiology, School of Medicine, New York University, New York, NY 10010, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary","family":"DeRome","sequence":"additional","affiliation":[{"name":"Artificial Cell Technologies, Inc., 5 Science Park, Suite 13, New Haven, CT 06511, USA"},{"name":"Multiple Myeloma Research Foundation, 383 Main Avenue, 5th Floor, Norwalk, CT 06851, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Jacobs","sequence":"additional","affiliation":[{"name":"Artificial Cell Technologies, Inc., 5 Science Park, Suite 13, New Haven, CT 06511, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naveen","family":"Palath","sequence":"additional","affiliation":[{"name":"Artificial Cell Technologies, Inc., 5 Science Park, Suite 13, New Haven, CT 06511, USA"},{"name":"Pfizer, Inc., Andover, MA 01810, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edwin","family":"Cardenas","sequence":"additional","affiliation":[{"name":"Artificial Cell Technologies, Inc., 5 Science Park, Suite 13, New Haven, CT 06511, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Yorke","sequence":"additional","affiliation":[{"name":"Artificial Cell Technologies, Inc., 5 Science Park, Suite 13, New Haven, CT 06511, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Boyd","sequence":"additional","affiliation":[{"name":"Artificial Cell Technologies, Inc., 5 Science Park, Suite 13, New Haven, CT 06511, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Kaba","sequence":"additional","affiliation":[{"name":"Malaria Vaccine Branch, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA"},{"name":"GreenLight Biosciences, Inc., Lexington, MA 02421, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Nardin","sequence":"additional","affiliation":[{"name":"Department of Microbiology, School of Medicine, New York University, New York, NY 10010, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,30]]},"reference":[{"key":"ref_1","unstructured":"WHO (2022). 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