A ferritin-based COVID-19 nanoparticle vaccine that elicits robust, durable, broad-spectrum neutralizing antisera in non-human primates

Weidenbacher, Payton A.; Sanyal, Mrinmoy; Friedland, Natalia; Tang, Shaogeng; Arunachalam, Prabhu S.; Hu, Mary Y.; Kumru, Ozan S.; Fontenot, Jane; Shirreff, Lisa; Do, Jonathan; Cheng, Ya-Chen; Vasudevan, Gayathri; Feinberg, Mark B.; Villinger, François; Hanson, Carl V.; Joshi, Sangeeta B.; Volkin, David B.; Pulendran, Bali; Kim, Peter S.

doi:10.1038/s41467-023-37417-9

Cited by 44 publications

(42 citation statements)

References 75 publications

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“…Previously, an RBD-HR chimeric ferritin nanoparticle vaccine elicited neutralizing titers comparable to an RBD- ferritin nanoparticle in mice but with broader cross-neutralization potential against other coronaviruses ( 58 ). Another Ferritin displayed, alum adjuvanted Spike construct also displayed promising immunogenicity in non-human primates and could be stored at 37°C for at least two weeks ( 59 ). The present RS2 immunogen elicited a significantly higher humoral immune response and protection against the Beta variant in hamsters compared to both the Spike ectodomain as well as RBD, the latter also required three immunizations in hamsters to elicit protective antibody titers ( 24 ).…”

Section: Discussionmentioning

confidence: 99%

Enhanced protective efficacy of a novel, thermostable, RBD-S2 vaccine formulation against SARS-CoV-2 and its variants

Mittal

Kumar

Rajmani

et al. 2023

Preprint

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With the rapid emergence of variants of concern (VOC), the efficacy of currently licensed vaccines has reduced drastically. VOC mutations largely occur in the S1 subunit of Spike. The S2 subunit of SARS-CoV-2 is conserved and thus more likely to elicit broadly protective antibody and T-cell responses. However, the contribution of the S2 subunit in improving the overall efficacy of vaccines remains unclear. Therefore, we designed, characterized, and evaluated the immunogenicity and protective potential of a stabilized SARS-CoV-2 Receptor Binding Domain (RBD) fused to a stabilized S2. Designed immunogens were expressed as soluble proteins with significantly higher purified yield than the Spike ectodomain. Squalene-in-water emulsion (SWE) formulated fusions were highly immunogenic. S2 immunization failed to elicit a neutralizing immune response but significantly reduced lung viral titers in mice challenged with the heterologous Beta variant, while RBD-S2 fusions elicited broad neutralization including against the Clade 1a WIV-1 variant, and were highly efficacious. A lyophilized RBD-S2 fusion retained antigenicity and immunogenicity even after incubation at 37 degrees C for a month. In hamsters, SWE-formulated RBD-S2 showed enhanced immunogenicity and efficacy relative to corresponding RBD and Spike formulations.

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Section: Discussionmentioning

confidence: 99%

Enhanced protective efficacy of a novel, thermostable, RBD-S2 vaccine formulation against SARS-CoV-2 and its variants

Mittal

Kumar

Rajmani

et al. 2023

Preprint

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“…Ferritin nanoparticle vaccines have emerged as a promising platform for vaccine production. These vaccines have shown notable effects on immune responses to the influenza virus, COVID-19, and γ-herpes virus. − The highly symmetric arrangement of repetitive units in ferritin self-assembled nanoparticle vaccines has been found to induce a stronger and longer-lasting immune response compared to conventional vaccines. In 2013, Kanekiyo et al conducted a gene fusion experiment, combining ferritin and the hemagglutinin of H1N1 virus.…”

Section: Application Of Ferritin Nanocagesmentioning

confidence: 99%

Advancements of the Molecular Directed Design and Structure–Activity Relationship of Ferritin Nanocage

Xia,

Li,

Zang

et al. 2024

J. Agric. Food Chem.

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Ferritin nanocages possess remarkable structural properties and biological functions, making them highly attractive for applications in functional materials and biomedicine. This comprehensive review presents an overview of the molecular characteristics, extraction and identification of ferritin, ferritin receptors, as well as the advancements in the directional design of high-order assemblies of ferritin and the applications based on its unique structural properties. Specifically, this Review focuses on the regulation of ferritin assembly from one to three dimensions, leveraging the symmetry of ferritin and modifications on key interfaces. Furthermore, it discusses targeted delivery of nutrition and drugs through facile loading and functional modification of ferritin. The aim of this Review is to inspire the design of micro/nano functional materials using ferritin and the development of nanodelivery vehicles for nutritional fortification and disease treatment.

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“…Tethering the glycoproteins to a NP adds another variable to the interplay between structure and dynamics that must be tested on a case-by-case basis. successfully in this context in other systems, most notably for SARS-CoV-2 spike, [159][160][161][162] so it appears to be a matter of matching the antigen to its most appropriate NP platform. For HCV E1E2, this represents an experimental challenge waiting to be met.…”

Section: Future Prospects For a Np-based Hcv Vaccinementioning

confidence: 99%

Prospects for developing an Hepatitis C virus E1E2‐based nanoparticle vaccine

Toth

Andrianov

Fuerst

2023

Reviews in Medical Virology

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Globally, more than 58 million people are chronically infected with Hepatitis C virus (HCV) with 1.5 million new infections occurring each year. An effective vaccine for HCV is therefore a major unmet medical and public health need. Since HCV rapidly accumulates mutations, vaccines must elicit the production of broadly neutralising antibodies (bnAbs) in a reproducible fashion. Decades of research have generated a number of HCV vaccine candidates. Based on the available data and research through clinical development, a vaccine antigen based on the E1E2 glycoprotein complex appears to be the best choice, but robust induction of humoral and cellular responses leading to virus neutralisation has not yet been achieved. One issue that has arisen in developing an HCV vaccine (and many other vaccines as well) is the platform used for antigen delivery. The majority of viral vaccine trials have employed subunit vaccines. However, subunit vaccines often have limited immunogenicity, as seen for HCV, and thus multiple formats must be examined in order to elicit a robust anti‐HCV immune response. Nanoparticle vaccines are gaining prominence in the field due to their ability to facilitate a controlled multivalent presentation and trafficking to lymph nodes, where they can interact with both arms of the immune system. This review discusses the potential for development of a nanoparticle‐based HCV E1E2 vaccine, with an emphasis on the potential benefits of such an approach along with the major challenges facing the incorporation of E1E2 into nanoparticulate delivery systems and how those challenges can be addressed.

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A ferritin-based COVID-19 nanoparticle vaccine that elicits robust, durable, broad-spectrum neutralizing antisera in non-human primates

Cited by 44 publications

References 75 publications

Enhanced protective efficacy of a novel, thermostable, RBD-S2 vaccine formulation against SARS-CoV-2 and its variants

Enhanced protective efficacy of a novel, thermostable, RBD-S2 vaccine formulation against SARS-CoV-2 and its variants

Advancements of the Molecular Directed Design and Structure–Activity Relationship of Ferritin Nanocage

Prospects for developing an Hepatitis C virus E1E2‐based nanoparticle vaccine

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