Morphological characterization of a plant-made virus-like particle vaccine bearing influenza virus hemagglutinins by electron microscopy

Lindsay, Brianne J; Bonar, Michał M.; Costas-Cancelas, Ian N; Hunt, Kristin; Makarkov, Alexander; Chierzi, Sabrina; Krawczyk, Connie M.; Landry, Nathalie; Ward, Brian J.; Rouiller, Isabelle

doi:10.1016/j.vaccine.2018.02.106

Cited by 43 publications

(35 citation statements)

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“…Irina Tretyakova and her colleague reported a quadrivalent pseudotype influenza VLP vaccine containing four different types of HA (H5N1, H7N9, H9N2, and H10N8) proteins, NA and bovine immunodeficiency virus gag protein (B gag) as an alternative to M1 matrix protein in insect cells [62] ( Table 2). Electron microscopic observation results [44] demonstrated that average sizes of the B gag core protein assembled VLPs are in a range of 150 nm to 200 nm, which was larger than the influenza virus M1 core protein assembled VLPs.…”

Section: Influenza Vlp Vaccine Against Potential Pandemic Influenza Vmentioning

confidence: 92%

“…VLPs obtained by harvesting plant cells, homogenizing, and purification. Plant-made VLPs showed morphological stable structures over time, eliciting both humoral and cellular responses in mice, ferrets, rabbits, or chickens [43][44][45] (Tables 1, 2 , 4). A plant-derived H1-VLP vaccine was reported to induce significantly higher levels of IgG antibodies, CD4 + , and CD8 + T cell responses compared to inactivated virus vaccine in aged mice [45].…”

Section: Production and Immunogenicity Of Influenza Vlp Vaccines Targmentioning

confidence: 99%

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Progress in the development of virus-like particle vaccines against respiratory viruses

Quan

Basak

Chu

et al. 2020

Expert Review of Vaccines

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Introduction: Influenza virus, human respiratory syncytial virus (RSV), and human metapneumovirus (HMPV) are important human respiratory pathogens. Recombinant virus-like particle (VLP) vaccines are suggested to be potential promising platforms to protect against these respiratory viruses. This review updates important progress in the development of VLP vaccines against respiratory viruses. Areas Covered: This review summarizes progress in developing VLP and nanoparticle-based vaccines against influenza virus, RSV, and HMPV. The PubMed was mainly used to search for important research articles published since 2010 although earlier key articles were also referenced. The research area covered includes VLP and nanoparticle platform vaccines against seasonal, pandemic, and avian influenza viruses as well as RSV and HMPV respiratory viruses. The production methods, immunogenic properties, and vaccine efficacy of respiratory VLP vaccines in preclinical animal models and clinical studies were reviewed in this article. Expert opinion: Previous and current preclinical and clinical studies suggest that recombinant VLP and nanoparticle vaccines are expected to be developed as promising alternative platforms against respiratory viruses in future. Therefore, continued research efforts are warranted. ARTICLE HISTORY

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Section: Influenza Vlp Vaccine Against Potential Pandemic Influenza Vmentioning

confidence: 92%

Section: Production and Immunogenicity Of Influenza Vlp Vaccines Targmentioning

confidence: 99%

Progress in the development of virus-like particle vaccines against respiratory viruses

Quan

Basak

Chu

et al. 2020

Expert Review of Vaccines

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“…Tomographic imaging of Influenza hemagglutinin-based VLPs transiently expressed in plants also showed that these enveloped virus VLPs are morphologically similar to Influenza virions, although the distance between hemagglutinin trimers was slightly greater on the VLP (Figure 2d). The authors hint at a relationship between this distance and immunogenicity, and show that the VLPs preserve native interactions with immune cells [27]. Similar plant-made particles have completed Phase II clinical trials [28].…”

Section: Structurally Authentic Vaccinesmentioning

confidence: 99%

“…(c) Cryo-EM reconstruction of the Atlantic Cod Nervous necrosis virus VLP to 3.7 Å for shell domain (in blue) and lower resolution for the trimeric protrusions flexible P domain [26]. (d) Influenza reconstructed by cryo-electron tomography generated from a tilt series of images of individual particles showing trimeric hemagglutinin in purple [27]. (i) Discoid particles comprising >65% of particles in the preparation, (ii) spherical particles comprising 30% of particles in the preparation (a small number of star-shaped hemagglutinin rosettes were also observed), (iii) close-up of discoid particle showing hemagglutinin trimers are separated by approximately 200 nm, which is around two times the spacing found on the native virion.…”

Section: å 176 å Current Opinion In Biotechnologymentioning

confidence: 99%

Innovation in plant-based transient protein expression for infectious disease prevention and preparedness

Sainsbury

2020

Current Opinion in Biotechnology

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Addressing new challenges in global health and biosecurity requires responsive and accessible platforms for the manufacture of preventative or therapeutic interventions. Transient protein expression in plants has evolved into a technology that offers a unique combination of rapid expression, inherent scalability, and flexibility in gene stacking with the capability to produce complex proteins and protein assemblies. Technical developments that have driven the progress of transient expression in plants include advanced expression systems, protein engineering and synthetic biology approaches to transiently, or stably, modify host plants. The plasticity of transient expression in plants, speed of scalability and relatively low capital costs, highlight the great potential of this technology in the future of human and animal health.Addresses

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“…[6,7] This VLP has been extensively characterized biochemically and is morphologically similar to the influenza virus. [8,9] The production process also includes a viral inactivation step that uses ultraviolet C (UVC) light to induce nucleic acid damage to adventitious agents that could theoretically be present in the process stream. [10] The regulatory requirement that a viral inactivation step be included in a process that uses no animal-derived raw materials and uses a plant as the host cell production system may appear, at first glance, to be unnecessary.…”

Section: Medicago's Vaccinementioning

confidence: 99%

Investigation of an Adventitious Agent Test False Positive Signal in a Plant-Derived Influenza Vaccine

Talarico¹,

Murphy²,

Nims³

et al. 2018

BioProcess J

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M edicago manufactures influenza vaccine virus-like particles (VLPs) in an unusual production platform consisting of Nicotiana benthamiana plants. During the in vitro adventitious agent test (AAT) of certain Medicago B strain influenza vaccine VLP test samples, positive hemagglutination of guinea pig red blood cells was observed on day 14, but not on day 28. The positive result in the assay was surprising because the production process uses no animal-derived raw materials and contains a viral inactivation step. Plant-associated viruses would not be expected to infect the mammalian cell-based assay. No cytopathic effects or hemadsorption of red blood cells was observed in these AATs. The positive hemagglutination was observed at 2-8°C, but not at 36-38 °C, and only in a few of the six detector cell lines used in the assay. Because this is quite an unusual pattern of responses for an AAT, Medicago and the contract testing lab, Eurofins Lancaster Laboratories (ELLI) investigated the positive responses thoroughly for the presence of an adventitious agent or an alternative explanation not involving a viral contaminant. Investigation results indicated that the hemagglutinating activity associated with the vaccine test sample itself was responsible for the positive hemagglutination response. The positive hemagglutination on day 14 of these AATs was deemed an assay artifact, and preventive actions were taken to prevent recurrence of this type of false positive response.

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Morphological characterization of a plant-made virus-like particle vaccine bearing influenza virus hemagglutinins by electron microscopy

Cited by 43 publications

References 49 publications

Progress in the development of virus-like particle vaccines against respiratory viruses

Progress in the development of virus-like particle vaccines against respiratory viruses

Innovation in plant-based transient protein expression for infectious disease prevention and preparedness

Investigation of an Adventitious Agent Test False Positive Signal in a Plant-Derived Influenza Vaccine

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