A Self-Assembling Ferritin Nanoplatform for Designing Classical Swine Fever Vaccine: Elicitation of Potent Neutralizing Antibody

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Abstract

Protein-based self-assembling nanoplatforms exhibit superior immunogenicity compared with soluble antigens. Here, we present a comprehensive vaccine strategy for displaying classical swine fever virus (CSFV) E2 glycoprotein on the surface of ferritin (fe) nanocages. An E2-specific blocking antibody assay showed that the blocking rates in pE2-fe/Gel02 (84.3%) and a half-dose cohort of E2-fe/Gel02 (81.9%) were significantly higher ( p < 0.05) than that in a ferritin-free cohort of pE2/Gel02 (62.7%) at 21 days post immunization (dpi) in vivo. Furthermore, quantitation of neutralizing potency revealed that a highly significant difference ( p < 0.001) was observed between the pE2-fe/Gel02 cohort (1:32, equivalent to live-attenuated strain C at 1:32) and the pE2/Gel02 cohort (1:4) at 21 dpi. Moreover, the innate immune cytokines of IL-4 and IFN-γ activated by the half-dose (20 μg) cohort of E2-fe/Gel02 were equivalent to those elicited by the full dose (40 μg) of purified E2 in the pE2/Gel02 cohort at most time points. In conclusion, we successfully obtained an antigen-displaying E2-ferritin nanoplatform and confirmed high ferritin-assisted humoral and cellular immunities. Our results provided a novel paradigm of self-assembling nanovaccine development for the defense and elimination of potentially pandemic infectious viral pathogens.

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Self-assembling influenza nanoparticle vaccines elicit broadly neutralizing H1N1 antibodies.

Masaru Kanekiyo, Chih-Jen Wei, Hadi M Yassine … (2013)

Influenza viruses pose a significant threat to the public and are a burden on global health systems. Each year, influenza vaccines must be rapidly produced to match circulating viruses, a process constrained by dated technology and vulnerable to unexpected strains emerging from humans and animal reservoirs. Here we use knowledge of protein structure to design self-assembling nanoparticles that elicit broader and more potent immunity than traditional influenza vaccines. The viral haemagglutinin was genetically fused to ferritin, a protein that naturally forms nanoparticles composed of 24 identical polypeptides. Haemagglutinin was inserted at the interface of adjacent subunits so that it spontaneously assembled and generated eight trimeric viral spikes on its surface. Immunization with this influenza nanoparticle vaccine elicited haemagglutination inhibition antibody titres more than tenfold higher than those from the licensed inactivated vaccine. Furthermore, it elicited neutralizing antibodies to two highly conserved vulnerable haemagglutinin structures that are targets of universal vaccines: the stem and the receptor binding site on the head. Antibodies elicited by a 1999 haemagglutinin-nanoparticle vaccine neutralized H1N1 viruses from 1934 to 2007 and protected ferrets from an unmatched 2007 H1N1 virus challenge. This structure-based, self-assembling synthetic nanoparticle vaccine improves the potency and breadth of influenza virus immunity, and it provides a foundation for building broader vaccine protection against emerging influenza viruses and other pathogens.

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Self-assembling protein nanoparticles in the design of vaccines

Jacinto López-Sagaseta, Enrico Malito, Rino Rappuoli … (2015)

For over 100 years, vaccines have been one of the most effective medical interventions for reducing infectious disease, and are estimated to save millions of lives globally each year. Nevertheless, many diseases are not yet preventable by vaccination. This large unmet medical need demands further research and the development of novel vaccines with high efficacy and safety. Compared to the 19th and early 20th century vaccines that were made of killed, inactivated, or live-attenuated pathogens, modern vaccines containing isolated, highly purified antigenic protein subunits are safer but tend to induce lower levels of protective immunity. One strategy to overcome the latter is to design antigen nanoparticles: assemblies of polypeptides that present multiple copies of subunit antigens in well-ordered arrays with defined orientations that can potentially mimic the repetitiveness, geometry, size, and shape of the natural host-pathogen surface interactions. Such nanoparticles offer a collective strength of multiple binding sites (avidity) and can provide improved antigen stability and immunogenicity. Several exciting advances have emerged lately, including preclinical evidence that this strategy may be applicable for the development of innovative new vaccines, for example, protecting against influenza, human immunodeficiency virus, and respiratory syncytial virus. Here, we provide a concise review of a critical selection of data that demonstrate the potential of this field. In addition, we highlight how the use of self-assembling protein nanoparticles can be effectively combined with the emerging discipline of structural vaccinology for maximum impact in the rational design of vaccine antigens.

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Detection of Viral Infections by Innate Immunity

Michael Carty, Coralie Guy, Andrew G Bowie (2021)

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Journal

Journal ID (nlm-ta): Vaccines (Basel)

Journal ID (iso-abbrev): Vaccines (Basel)

Journal ID (publisher-id): vaccines

Title: Vaccines

Publisher: MDPI

ISSN (Electronic): 2076-393X

Publication date (Electronic): 13 January 2021

Publication date Collection: January 2021

Volume: 9

Issue: 1

Electronic Location Identifier: 45

Affiliations

[1 ]State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070, China; zekaizhao@ 123456yeah.net (Z.Z.); cxhdeyx129@ 123456163.com (X.C.); yibaochen@ 123456webmail.hzau.edu.cn (Y.C.); huilihzau@ 123456yeah.net (H.L.); fangkui1987@ 123456126.com (K.F.); liuchenxinxin@ 123456163.com (H.C.); lixiangmin@ 123456mail.hzau.edu.cn (X.L.)

[2 ]College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China

Author notes

[* ]Correspondence: qianp@ 123456mail.hzau.edu.cn ; Tel./Fax: +86-27-8728-2608

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Zekai Zhao https://orcid.org/0000-0002-3816-5471

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Publisher ID: vaccines-09-00045

DOI: 10.3390/vaccines9010045

PMC ID: 7828615

PubMed ID: 33451123

SO-VID: 53d1380a-db33-473b-981c-25a614272074

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Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

A Self-Assembling Ferritin Nanoplatform for Designing Classical Swine Fever Vaccine: Elicitation of Potent Neutralizing Antibody

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Abstract

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Malaria vaccine development

Most cited references 35

Self-assembling influenza nanoparticle vaccines elicit broadly neutralizing H1N1 antibodies.

Self-assembling protein nanoparticles in the design of vaccines

Detection of Viral Infections by Innate Immunity

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