PfCSP-ferritin nanoparticle malaria vaccine antigen formulated with aluminum-salt and CpG 1018® adjuvants: Preformulation characterization, antigen-adjuvant interactions, and mouse immunogenicity studies.
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 Information
John M Hickey: Department of Pharmaceutical Chemistry, Vaccine Analytics and Formulation Center, University of Kansas, Lawrence, KS, USA.
Nitya Sharma: Department of Pharmaceutical Chemistry, Vaccine Analytics and Formulation Center, University of Kansas, Lawrence, KS, USA.
Max Fairlamb: Department of Pharmaceutical Chemistry, Vaccine Analytics and Formulation Center, University of Kansas, Lawrence, KS, USA.
Jennifer Doering: Division of Infectious Disease, Wadsworth Center, New York State Department of Health, Albany, NY, USA.
Yetunde Adewunmi: Division of Infectious Disease, Wadsworth Center, New York State Department of Health, Albany, NY, USA.
Katherine Prieto: Program in Molecular Medicine, The Hospital for Sick Children, Research Institute, Toronto, ON, Canada.
Giulia Costa: Vector Biology Unit, Max Planck Institute for Infection Biology, Berlin, Germany.
Benjamin Wizel: Head of External Research and Development, Dynavax Technologies Corporation, Emeryville, CA, USA.
Elena A Levashina: Vector Biology Unit, Max Planck Institute for Infection Biology, Berlin, Germany.
Nicholas J Mantis: Division of Infectious Disease, Wadsworth Center, New York State Department of Health, Albany, NY, USA.
Jean-Philippe Julien: Program in Molecular Medicine, The Hospital for Sick Children, Research Institute, Toronto, ON, Canada.
Sangeeta B Joshi: Department of Pharmaceutical Chemistry, Vaccine Analytics and Formulation Center, University of Kansas, Lawrence, KS, USA.
David B Volkin: Department of Pharmaceutical Chemistry, Vaccine Analytics and Formulation Center, University of Kansas, Lawrence, KS, USA.
Circumsporozite protein (CSP), the most abundant surface protein in parasitic (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 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 antigenicity of the 155 antigen was measured upon formulation with adjuvants, including aluminum-salts (i.e. Alhydrogel, Adju-Phos) and the TLR-9 agonist CpG 1018®, when freshly combined and after storage at different temperatures over 3 months. The immunological impact of various adjuvanted formulations of the 155 antigen was investigated in mice. The results support the formulation of 155 with Alhydrogel + CpG 1018® adjuvants as a promising recombinant malaria vaccine candidate from both a pharmaceutical and immunological perspective.
