PfCSP-ferritin nanoparticle malaria vaccine antigen formulated with aluminum-salt and CpG 1018® adjuvants: Preformulation characterization, antigen-adjuvant interactions, and mouse immunogenicity studies
Circumsporozite protein (CSP), the most abundant surface protein in parasitic Plasmodium falciparum (Pf) sporozoite and an attractive target for malaria vaccine design, has been shown to induce protective humoral response in humans. In this work, we characterized and formulated a promising recombina...
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Taylor & Francis Group
2025-12-01
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| Series: | Human Vaccines & Immunotherapeutics |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/21645515.2025.2460749 |
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| author | John M. Hickey Nitya Sharma Max Fairlamb Jennifer Doering Yetunde Adewunmi Katherine Prieto Giulia Costa Benjamin Wizel Elena A. Levashina Nicholas J. Mantis Jean-Philippe Julien Sangeeta B. Joshi David B. Volkin |
| author_facet | John M. Hickey Nitya Sharma Max Fairlamb Jennifer Doering Yetunde Adewunmi Katherine Prieto Giulia Costa Benjamin Wizel Elena A. Levashina Nicholas J. Mantis Jean-Philippe Julien Sangeeta B. Joshi David B. Volkin |
| author_sort | John M. Hickey |
| collection | DOAJ |
| description | Circumsporozite protein (CSP), the most abundant surface protein in parasitic Plasmodium falciparum (Pf) sporozoite and an attractive target for malaria vaccine design, has been shown to induce protective humoral response in humans. In this work, we characterized and formulated a promising recombinant PfCSP immunogen (155) candidate consisting of two PfCSP epitopes (i.e. junction, NANP repeat) fused to H. pylori apoferritin forming a 24-mer nanoparticle. In addition, two N-linked glycans were engineered to mitigate possible anti-apoferritin immune responses, and a universal T-cell epitope was included to further enhance immunogenicity. Physicochemical characterization of the 155 antigen was performed including primary structure, post-translational modifications, conformational stability, and particle size. A competitive ELISA was developed to assess antigen binding to a PfCSP-specific mAb. The in vitro antigenicity of the 155 antigen was measured upon formulation with adjuvants, including aluminum-salts (i.e. AlhydrogelTM, Adju-PhosTM) and the TLR-9 agonist CpG 1018®, when freshly combined and after storage at different temperatures over 3 months. The in vivo immunological impact of various adjuvanted formulations of the 155 antigen was investigated in mice. The results support the formulation of 155 with AlhydrogelTM + CpG 1018® adjuvants as a promising recombinant malaria vaccine candidate from both a pharmaceutical and immunological perspective. |
| format | Article |
| id | doaj-art-8e74ad6586b34b64b784d4aded516e7a |
| institution | Kabale University |
| issn | 2164-5515 2164-554X |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Human Vaccines & Immunotherapeutics |
| spelling | doaj-art-8e74ad6586b34b64b784d4aded516e7a2025-02-04T14:46:39ZengTaylor & Francis GroupHuman Vaccines & Immunotherapeutics2164-55152164-554X2025-12-0121110.1080/21645515.2025.2460749PfCSP-ferritin nanoparticle malaria vaccine antigen formulated with aluminum-salt and CpG 1018® adjuvants: Preformulation characterization, antigen-adjuvant interactions, and mouse immunogenicity studiesJohn M. Hickey0Nitya Sharma1Max Fairlamb2Jennifer Doering3Yetunde Adewunmi4Katherine Prieto5Giulia Costa6Benjamin Wizel7Elena A. Levashina8Nicholas J. Mantis9Jean-Philippe Julien10Sangeeta B. Joshi11David B. Volkin12Department of Pharmaceutical Chemistry, Vaccine Analytics and Formulation Center, University of Kansas, Lawrence, KS, USADepartment of Pharmaceutical Chemistry, Vaccine Analytics and Formulation Center, University of Kansas, Lawrence, KS, USADepartment of Pharmaceutical Chemistry, Vaccine Analytics and Formulation Center, University of Kansas, Lawrence, KS, USADivision of Infectious Disease, Wadsworth Center, New York State Department of Health, Albany, NY, USADivision of Infectious Disease, Wadsworth Center, New York State Department of Health, Albany, NY, USAProgram in Molecular Medicine, The Hospital for Sick Children, Research Institute, Toronto, ON, CanadaVector Biology Unit, Max Planck Institute for Infection Biology, Berlin, GermanyHead of External Research and Development, Dynavax Technologies Corporation, Emeryville, CA, USAVector Biology Unit, Max Planck Institute for Infection Biology, Berlin, GermanyDivision of Infectious Disease, Wadsworth Center, New York State Department of Health, Albany, NY, USAProgram in Molecular Medicine, The Hospital for Sick Children, Research Institute, Toronto, ON, CanadaDepartment of Pharmaceutical Chemistry, Vaccine Analytics and Formulation Center, University of Kansas, Lawrence, KS, USADepartment of Pharmaceutical Chemistry, Vaccine Analytics and Formulation Center, University of Kansas, Lawrence, KS, USACircumsporozite protein (CSP), the most abundant surface protein in parasitic Plasmodium falciparum (Pf) sporozoite and an attractive target for malaria vaccine design, has been shown to induce protective humoral response in humans. In this work, we characterized and formulated a promising recombinant PfCSP immunogen (155) candidate consisting of two PfCSP epitopes (i.e. junction, NANP repeat) fused to H. pylori apoferritin forming a 24-mer nanoparticle. In addition, two N-linked glycans were engineered to mitigate possible anti-apoferritin immune responses, and a universal T-cell epitope was included to further enhance immunogenicity. Physicochemical characterization of the 155 antigen was performed including primary structure, post-translational modifications, conformational stability, and particle size. A competitive ELISA was developed to assess antigen binding to a PfCSP-specific mAb. The in vitro antigenicity of the 155 antigen was measured upon formulation with adjuvants, including aluminum-salts (i.e. AlhydrogelTM, Adju-PhosTM) and the TLR-9 agonist CpG 1018®, when freshly combined and after storage at different temperatures over 3 months. The in vivo immunological impact of various adjuvanted formulations of the 155 antigen was investigated in mice. The results support the formulation of 155 with AlhydrogelTM + CpG 1018® adjuvants as a promising recombinant malaria vaccine candidate from both a pharmaceutical and immunological perspective.https://www.tandfonline.com/doi/10.1080/21645515.2025.2460749Malaria vaccineAlhydrogelAdju-phosCpG 1018®AdjuvantPfCSP |
| spellingShingle | John M. Hickey Nitya Sharma Max Fairlamb Jennifer Doering Yetunde Adewunmi Katherine Prieto Giulia Costa Benjamin Wizel Elena A. Levashina Nicholas J. Mantis Jean-Philippe Julien Sangeeta B. Joshi David B. Volkin PfCSP-ferritin nanoparticle malaria vaccine antigen formulated with aluminum-salt and CpG 1018® adjuvants: Preformulation characterization, antigen-adjuvant interactions, and mouse immunogenicity studies Human Vaccines & Immunotherapeutics Malaria vaccine Alhydrogel Adju-phos CpG 1018® Adjuvant PfCSP |
| title | PfCSP-ferritin nanoparticle malaria vaccine antigen formulated with aluminum-salt and CpG 1018® adjuvants: Preformulation characterization, antigen-adjuvant interactions, and mouse immunogenicity studies |
| title_full | PfCSP-ferritin nanoparticle malaria vaccine antigen formulated with aluminum-salt and CpG 1018® adjuvants: Preformulation characterization, antigen-adjuvant interactions, and mouse immunogenicity studies |
| title_fullStr | PfCSP-ferritin nanoparticle malaria vaccine antigen formulated with aluminum-salt and CpG 1018® adjuvants: Preformulation characterization, antigen-adjuvant interactions, and mouse immunogenicity studies |
| title_full_unstemmed | PfCSP-ferritin nanoparticle malaria vaccine antigen formulated with aluminum-salt and CpG 1018® adjuvants: Preformulation characterization, antigen-adjuvant interactions, and mouse immunogenicity studies |
| title_short | PfCSP-ferritin nanoparticle malaria vaccine antigen formulated with aluminum-salt and CpG 1018® adjuvants: Preformulation characterization, antigen-adjuvant interactions, and mouse immunogenicity studies |
| title_sort | pfcsp ferritin nanoparticle malaria vaccine antigen formulated with aluminum salt and cpg 1018 r adjuvants preformulation characterization antigen adjuvant interactions and mouse immunogenicity studies |
| topic | Malaria vaccine Alhydrogel Adju-phos CpG 1018® Adjuvant PfCSP |
| url | https://www.tandfonline.com/doi/10.1080/21645515.2025.2460749 |
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