Formulation development and comparability studies with an aluminum-salt adjuvanted SARS-CoV-2 spike ferritin nanoparticle vaccine antigen produced from two different cell lines

Article

Author: Sanyal, Mrinmoy ; Weidenbacher, Payton ; Volkin, David B ; Hickey, John M ; Joshi, Richa ; Kumru, Ozan S ; Kim, Peter S ; Cheng, Ya-Chen ; Joshi, Sangeeta B ; Friedland, Natalia ; Do, Jonathan

The development of safe and effective second-generation COVID-19 vaccines to improve affordability and storage stability requirements remains a high priority to expand global coverage. In this report, we describe formulation development and comparability studies with a self-assembled SARS-CoV-2 spike ferritin nanoparticle vaccine antigen (called DCFHP), when produced in two different cell lines and formulated with an aluminum-salt adjuvant (Alhydrogel, AH). Varying levels of phosphate buffer altered the extent and strength of antigen-adjuvant interactions, and these formulations were evaluated for their (1) in vivo performance in mice and (2) in vitro stability profiles. Unadjuvanted DCFHP produced minimal immune responses while AH-adjuvanted formulations elicited greatly enhanced pseudovirus neutralization titers independent of ∼100%, ∼40% or ∼10% of the DCFHP antigen adsorbed to AH. These formulations differed, however, in their in vitro stability properties as determined by biophysical studies and a competitive ELISA for measuring ACE2 receptor binding of AH-bound antigen. Interestingly, after one month of 4°C storage, small increases in antigenicity with concomitant decreases in the ability to desorb the antigen from the AH were observed. Finally, we performed a comparability assessment of DCFHP antigen produced in Expi293 and CHO cells, which displayed expected differences in their N-linked oligosaccharide profiles. Despite consisting of different DCFHP glycoforms, these two preparations were highly similar in their key quality attributes including molecular size, structural integrity, conformational stability, binding to ACE2 receptor and mouse immunogenicity profiles. Taken together, these studies support future preclinical and clinical development of an AH-adjuvanted DCFHP vaccine candidate produced in CHO cells.

01 Sep 2023·Journal of medical virology

A conserved N protein nano-vaccine of COVID-19 exerts potent and cross-reactive humoral and cellular immune responses in mice.

Article

Author: Li, Bing ; Huang, Yang ; Zhang, Rongxin ; Li, Xinrui ; Zhang, Jing ; Feng, Jing ; Li, Yan

As severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) mutates continually, the current vaccines are unable to provide sufficient protection. It is important to develop a broad-spectrum vaccine with conserved antigens to prevent variant infection. Here we fused the SARS-CoV-2 N protein with Helicobacter pylori nonheme ferritin to construct a SARS-CoV-2 N-Ferritin nanoparticle vaccine. Compared with the monomer N protein, the N-Ferritin nanoparticles induced more lymph node dendritic cells in mice to trigger adoptive immunity. Following this, the N-Ferritin elicited more robust and long-lasting antibody responses, which had better cross-reactivity with the SARS-CoV N protein. It is also worth noting that higher levels of N-specific IgG and IgA were distributed in the lungs of N-Ferritin-immunized mice. Furthermore, the N-Ferritin nanoparticles also resulted higher proportion of interferon-γ⁺ CD8⁺ T cells, CD8⁺ Tcm cells, and T cells with cross-reactivity in SARS-CoV-2, SARS-CoV, and Middle East respiratory syndrome-related coronavirus. The conserved N-based nanoparticles could provide a promising vaccine developing strategy against SARS-CoV-2 variants and other coronaviruses.

16 Feb 2022·Science Translational MedicineQ1 · MEDICINE

A SARS-CoV-2 ferritin nanoparticle vaccine elicits protective immune responses in nonhuman primates

Q1 · MEDICINE

Article

Author: Peel, Sheila A. ; Daye, Sharon P. ; Choe, Misook ; Currier, Jeffrey R. ; Karasavva, Nicos ; Staples, Hilary M. ; Joyce, M. Gordon ; Ahmed, Aslaa ; Thomas, Paul V. ; Molnar, Sebastian ; Swafford, Isabella ; Bolton, Diane L. ; Amare, Mihret F. ; de Val, Natalia ; Cook, Anthony ; Diamond, Michael S. ; Paquin-Proulx, Dominic ; Martinez, Elizabeth J. ; Nair, Manoj S. ; Sankhala, Rajeshwer S. ; Ho, David D. ; Huang, Yaoxing ; Alfson, Kendra ; Anderson, Alexander ; Taddese, Mekdi G. ; Rao, Mangala ; Jagodzinski, Linda L. ; Zeng, Xiankun ; Peachman, Kristina K. ; Dussupt, Vincent ; Carrion, Ricardo ; Elakhal-Naouar, Ines ; Matyas, Gary R. ; Barkei, Erica K. ; King, Hannah A. D. ; Lewis, Mark G. ; Subra, Caroline ; Gromowski, Gregory D. ; Case, James Brett ; Chang, William C. ; McGuckin Wuertz, Kathryn ; Polonis, Victoria R. ; Scott, Paul T. ; Macedo Cincotta, Camila ; Dong, Ming ; Krebs, Shelly J. ; Lal, Kerri G. ; Modjarrad, Kayvon ; Chen, Wei-Hung ; Hajduczki, Agnes ; Peterson, Caroline E. ; Chen, Rita E. ; Headley, Jarrett A. ; Michael, Nelson L. ; Smith, Clayton ; Lee, Parker J. ; Vasan, Sandhya ; Elyard, Hanne A.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants stresses the continued need for next-generation vaccines that confer broad protection against coronavirus disease 2019. We developed and evaluated an adjuvanted SARS-CoV-2 spike ferritin nanoparticle (SpFN) vaccine in nonhuman primates. High-dose (50-μg) SpFN vaccine, given twice 28 days apart, induced a T helper cell 1 (T H 1)–biased CD4 T H response and elicited neutralizing antibodies against SARS-CoV-2 wild type and variants of concern, as well as against SARS-CoV-1. These potent humoral and cell-mediated immune responses translated into rapid elimination of replicating virus in the upper and lower airways and lung parenchyma of nonhuman primates after high-dose SARS-CoV-2 respiratory challenge. The immune response elicited by SpFN vaccination and resulting efficacy in nonhuman primates support the utility of SpFN as a vaccine candidate for SARS-causing betacoronaviruses.

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