Development of spike receptor-binding domain nanoparticle as a vaccine candidate against SARS-CoV-2 infection in ferrets

Kim, Young Il; Kim, Do Kyun; Yu, Kwang-Min; Seo, Hogyu David; Lee, Shin-Ae; Casel, Mark Anthony B.; Jang, Seung-Gyu; Kim, Stephanie; Jung, Wooram F.; Lai, Chih-Jen; Choi, Young Ki; Jung, Jae U.

doi:10.1101/2021.01.28.428743

Cited by 3 publications

(3 citation statements)

References 63 publications

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“…They also exhibited a neutralizing/binding ratio higher than that in convalescent human sera . Fusion of the RBD to Helicobacter pylori ferritin has also led to immunogenic, self-assembling nanoparticles in which the RBDs form radial multivalent projections that correctly expose their neutralizing epitopes …”

Section: Antigen Orientation and Multivalent Display In Rbd-based Vac...mentioning

confidence: 99%

“…71 Fusion of the RBD to Helicobacter pylori ferritin has also led to immunogenic, self-assembling nanoparticles in which the RBDs form radial multivalent projections that correctly expose their neutralizing epitopes. 80 A second approach is the use of a protein ligation technology 81 to conjugate several RBDs to the surface of preassembled nanoparticles. Examples are the construction of bacteriophage AP205 capsid-like particles decorated with multiple RBD copies 82 and the assembly of multicomponent ferritin-based nanoparticles 83 by ligating both the SARS-CoV-2 RBD and heptad repeat (HR) antigens to the ferritin nanocore.…”

Section: Antigen Orientation and Multivalent Display In Rbd-based Vac...mentioning

confidence: 99%

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Molecular Aspects Concerning the Use of the SARS-CoV-2 Receptor Binding Domain as a Target for Preventive Vaccines

et al. 2021

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The development of recombinant COVID-19 vaccines has resulted from scientific progress made at an unprecedented speed during 2020. The recombinant spike glycoprotein monomer, its trimer, and its recombinant receptorbinding domain (RBD) induce a potent anti-RBD neutralizing antibody response in animals. In COVID-19 convalescent sera, there is a good correlation between the antibody response and potent neutralization. In this review, we summarize with a critical view the molecular aspects associated with the interaction of SARS-CoV-2 RBD with its receptor in human cells, the angiotensin-converting enzyme 2 (ACE2), the epitopes involved in the neutralizing activity, and the impact of virus mutations thereof. Recent trends in RBD-based vaccines are analyzed, providing detailed insights into the role of antigen display and multivalence in the immune response of vaccines under development.

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Section: Antigen Orientation and Multivalent Display In Rbd-based Vac...mentioning

confidence: 99%

Section: Antigen Orientation and Multivalent Display In Rbd-based Vac...mentioning

confidence: 99%

Molecular Aspects Concerning the Use of the SARS-CoV-2 Receptor Binding Domain as a Target for Preventive Vaccines

et al. 2021

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“…The origin and transmission of CDV infections, particularly in non-canidae species, such as ferrets, is poorly understood (9,12,13). Ferrets are a widely used experimental animal to study the pathogenesis and transmission of a variety of viral diseases including influenza, SARS-CoV-1 and -2, Ebola, rabies and a range of paramyxoviruses (14,15), and are therefore an important animal to protect from unwanted, potentially fatal infections such as CDV.…”

Section: Introductionmentioning

confidence: 99%

A novel and highly divergent Canine Distemper Virus lineage causing distemper in ferrets in Australia

George

Wille

Wang

et al. 2021

Preprint

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Canine distemper virus (CDV) is a highly contagious systemic viral disease of dogs, that regularly spills-over into other animal species. Despite widespread vaccination, CDV remains endemic in many parts of the world. In this study we report an outbreak of distemper in ferrets in two independent research facilities in Australia. We found that disease severity varied, although most animals had mild to moderate disease signs. Histopathology results of animals with severe disease presented the typical profile of distemper pathology with multi-system virus replication. Through the development of a discriminatory PCR paired with full genome sequencing we revealed that the outbreak at both facilities was caused by a single, novel lineage of CDV. This lineage was highly divergent across the H gene, F signal peptide and full genome and had less than 93% similarity across the H gene to other described lineages, including the vaccine strain. Molecular analysis indicates that this strain belongs to a distinct lineage that diverged from other clades approximately 140 to 400 years ago, and appears to be unique to Australia. Given the differences in key viral proteins of this novel CDV strain, a review of the efficacy of the CDV vaccines currently in use in Australia is warranted to ensure maximum protection of dogs and other vulnerable species. In addition, enhanced surveillance to determine the prevalence of CDV in ferrets, dogs and other at-risk species in Australia would be useful to better understand the diversity of CDV in Australia.ImportanceCanine distemper virus (CDV) is highly contagious and while dogs are the main reservoir, it may spill over into a number of other animal species. In this study we report an outbreak of distemper in ferrets in two research facilities in Australia. Outcomes of pathology and histopathology suggest ferrets have widespread multi-systemic infection, consistent with previously reported distemper infections in ferrets and dogs. Critically, through sequencing and phylogenetic analysis, we revealed that the outbreak at both facilities was caused by a single, novel and highly divergent lineage of CDV. This virus had less than 93% nucleotide similarity to other described lineages and the vaccine strain. This manuscript adds considerably to the epidemiology, ecology and evolution of this virus, and is one of few reports of distemper in Australia in the literature.

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Development of KSHV vaccine platforms and chimeric MHV68-K-K8.1 glycoprotein for evaluating the in vivo immunogenicity and efficacy of KSHV vaccine candidates

Yang,

Kim,

Kang

et al. 2024

mBio

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Kaposi’s sarcoma-associated herpesvirus (KSHV)/human herpesvirus 8 is an etiological agent of Kaposi’s Sarcoma, multicentric Castleman’s disease, and primary effusion lymphoma. Considering the high seroprevalence reaching up to 80% in sub-Saharan Africa, an effective vaccine is crucial for preventing KSHV infection. However, vaccine development has been limited due to the lack of an effective animal model that supports KSHV infection. Murine Herpesvirus 68 (MHV68), a natural mouse pathogen persisting lifelong post-infection, presents a promising model for KSHV infection. In this study, we developed KSHV vaccine and a chimeric MHV68 carrying the KSHV glycoprotein, serving as a surrogate challenge virus for testing KSHV vaccines in a mouse model. Among KSHV virion glycoproteins, K8.1 is the most abundant envelope glycoprotein with the highest immunogenicity. We developed two K8.1 vaccines: K8.1 mRNA-lipid nanoparticle (LNP) vaccine and K8.1 26–87 -Ferritin (FT) nanoparticle vaccines. Both induced humoral responses in immunized mice, whereas K8.1 mRNA LNP also induced T cell responses. Using BACmid-mediated homologous recombination, the MHV68 M7 (gp150) gene was replaced with KSHV K8.1 gene to generate chimeric MHV68-K-K8.1. MHV68-K-K8.1 established acute and latent infection in the lungs and spleens of infected mice, respectively. Mice immunized with K8.1 mRNA LNP or K8.1 26–87 -FT showed a reduction of MHV68-K-K8.1 titer but not MHV68 wild type (WT) titer in the lung. In addition, viral reactivation of MHV68-K-K8.1 was also significantly reduced in K8.1 mRNA LNP-immunized mice. This study demonstrates the effectiveness of two vaccine candidates in providing immunity against KSHV K8.1 and introduces a surrogate MHV68 system for evaluating vaccine efficacy in vivo . IMPORTANCE Kaposi’s sarcoma-associated herpesvirus (KSHV) is a prevalent virus that establishes lifelong persistent infection in humans and is linked to several malignancies. While antiretroviral therapy has reduced Kaposi’s Sarcoma (KS) complications in people with HIV, KS still affects individuals with well-controlled HIV, older men without HIV, and transplant recipients. Despite its significant impact on human health, however, research on KSHV vaccine has been limited, mainly due to the lack of interest and the absence of a suitable animal model. This study addresses these challenges by developing KSHV K8.1 vaccine with two platforms, mRNA lipid nanoparticle (LNP) and FT nanoparticle. Additionally, chimeric virus, MHV68-K-K8.1, was created to evaluate KSHV vaccine efficacy in vivo . Vaccination of K8.1 mRNA LNP or K8.1 26–87 -FT significantly reduced MHV68-K-K8.1 titers. Developing an effective KSHV vaccine requires an innovative approach to ensure safety and efficacy, especially for the immunocompromised population and people with limited healthcare resources. This study could be a potential blueprint for future KSHV vaccine development.

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Development of spike receptor-binding domain nanoparticle as a vaccine candidate against SARS-CoV-2 infection in ferrets

Cited by 3 publications

References 63 publications

Molecular Aspects Concerning the Use of the SARS-CoV-2 Receptor Binding Domain as a Target for Preventive Vaccines

Molecular Aspects Concerning the Use of the SARS-CoV-2 Receptor Binding Domain as a Target for Preventive Vaccines

A novel and highly divergent Canine Distemper Virus lineage causing distemper in ferrets in Australia

Development of KSHV vaccine platforms and chimeric MHV68-K-K8.1 glycoprotein for evaluating the in vivo immunogenicity and efficacy of KSHV vaccine candidates

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