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      Integrating plant molecular farming and materials research for next-generation vaccines

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          Abstract

          Biologics — medications derived from a biological source — are increasingly used as pharmaceuticals, for example, as vaccines. Biologics are usually produced in bacterial, mammalian or insect cells. Alternatively, plant molecular farming, that is, the manufacture of biologics in plant cells, transgenic plants and algae, offers a cheaper and easily adaptable strategy for the production of biologics, in particular, in low-resource settings. In this Review, we discuss current vaccination challenges, such as cold chain requirements, and highlight how plant molecular farming in combination with advanced materials can be applied to address these challenges. The production of plant viruses and virus-based nanotechnologies in plants enables low-cost and regional fabrication of thermostable vaccines. We also highlight key new vaccine delivery technologies, including microneedle patches and material platforms for intranasal and oral delivery. Finally, we provide an outlook of future possibilities for plant molecular farming of next-generation vaccines and biologics.

          Abstract

          Cold chain requirements, distribution challenges and high costs limit the global rollout of many vaccines. This Review discusses plant molecular farming in combination with advanced materials strategies as a new platform for the local production of thermostable vaccines and other biologics.

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          Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK

          Background A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. Methods This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. Findings Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0–75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4–97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; p interaction =0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8–80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3–4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. Interpretation ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials. Funding UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, Bill & Melinda Gates Foundation, Lemann Foundation, Rede D’Or, Brava and Telles Foundation, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca.
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            Alginate: properties and biomedical applications.

            Alginate is a biomaterial that has found numerous applications in biomedical science and engineering due to its favorable properties, including biocompatibility and ease of gelation. Alginate hydrogels have been particularly attractive in wound healing, drug delivery, and tissue engineering applications to date, as these gels retain structural similarity to the extracellular matrices in tissues and can be manipulated to play several critical roles. This review will provide a comprehensive overview of general properties of alginate and its hydrogels, their biomedical applications, and suggest new perspectives for future studies with these polymers.
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              Poly Lactic-co-Glycolic Acid (PLGA) as Biodegradable Controlled Drug Delivery Carrier.

              In past two decades poly lactic-co-glycolic acid (PLGA) has been among the most attractive polymeric candidates used to fabricate devices for drug delivery and tissue engineering applications. PLGA is biocompatible and biodegradable, exhibits a wide range of erosion times, has tunable mechanical properties and most importantly, is a FDA approved polymer. In particular, PLGA has been extensively studied for the development of devices for controlled delivery of small molecule drugs, proteins and other macromolecules in commercial use and in research. This manuscript describes the various fabrication techniques for these devices and the factors affecting their degradation and drug release.
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                Author and article information

                Contributors
                ed.rybicki@uct.ac.za
                jpokorski@ucsd.edu
                nsteinmetz@ucsd.edu
                Journal
                Nat Rev Mater
                Nat Rev Mater
                Nature Reviews. Materials
                Nature Publishing Group UK (London )
                2058-8437
                6 December 2021
                : 1-17
                Affiliations
                [1 ]GRID grid.266100.3, ISNI 0000 0001 2107 4242, Department of Bioengineering, , University of California, San Diego, ; La Jolla, CA USA
                [2 ]GRID grid.266100.3, ISNI 0000 0001 2107 4242, Department of Nanoengineering, , University of California, San Diego, ; La Jolla, CA USA
                [3 ]Department of Radiology, University of California, San Diego Health, La Jolla, CA USA
                [4 ]GRID grid.266100.3, ISNI 0000 0001 2107 4242, Biomedical Science Program, , University of California, San Diego, ; La Jolla, CA USA
                [5 ]GRID grid.7836.a, ISNI 0000 0004 1937 1151, Department of Molecular and Cell Biology, , University of Cape Town, ; Cape Town, South Africa
                [6 ]GRID grid.266100.3, ISNI 0000 0001 2107 4242, Institute for Materials Discovery and Design, , University of California, San Diego, ; La Jolla, CA USA
                [7 ]GRID grid.266100.3, ISNI 0000 0001 2107 4242, Center for Nano-Immuno Engineering, , University of California, San Diego, ; La Jolla, CA USA
                [8 ]GRID grid.266100.3, ISNI 0000 0001 2107 4242, Moores Cancer Center, , University of California, San Diego, ; La Jolla, CA USA
                Author information
                http://orcid.org/0000-0002-6578-8076
                http://orcid.org/0000-0002-7260-9507
                http://orcid.org/0000-0002-0130-0481
                Article
                399
                10.1038/s41578-021-00399-5
                8647509
                34900343
                a976ad03-488e-4fe0-94a0-371f29c5ebb2
                © Springer Nature Limited 2021

                This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

                History
                : 18 October 2021
                Categories
                Review Article

                plant biotechnology,protein vaccines,vaccines
                plant biotechnology, protein vaccines, vaccines

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