13
views
0
recommends
+1 Recommend
1 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      An mRNA-based vaccine candidate against SARS-CoV-2 elicits stable immuno-response with single dose

      research-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          D614G genotype of SARS-CoV-2 virus is highly infectious and responsible for almost all infection for 2 nd wave. However, there are currently no reports with D614G as vaccine candidate. Here we report the development of an mRNA-LNP vaccine with D614G variant and characterization in animal model. We have used special mRNA-architecture and formulation that provides suitable response of the product. The surface plasmon resonance (SPR) data with spike protein (S) revealed that immunization generated specific antibody pools against the whole extracellular domain (RBD and S2) of the spike protein. The anti-sera and purified IgGs from immunized mice neutralized SARS-CoV-2-pseudoviruses in ACE2-expressing HEK293 cells in a dose dependent manner. Importantly, single-dose immunization protected mice-lungs from homotypic-pseudovirus entry and cytopathy. The immunologic responses have been implicated by a balanced and stable population of CD4+ cells with a Th1 bias. The data suggested great promise for immediate translation of the technology to the clinic.

          Related collections

          Most cited references28

          • Record: found
          • Abstract: found
          • Article: not found

          Tracking changes in SARS-CoV-2 Spike: evidence that D614G increases infectivity of the COVID-19 virus

          Summary A SARS-CoV-2 variant carrying the Spike protein amino acid change D614G has become the most prevalent form in the global pandemic. Dynamic tracking of variant frequencies revealed a recurrent pattern of G614 increase at multiple geographic levels: national, regional and municipal. The shift occurred even in local epidemics where the original D614 form was well established prior to the introduction of the G614 variant. The consistency of this pattern was highly statistically significant, suggesting that the G614 variant may have a fitness advantage. We found that the G614 variant grows to higher titer as pseudotyped virions. In infected individuals G614 is associated with lower RT-PCR cycle thresholds, suggestive of higher upper respiratory tract viral loads, although not with increased disease severity. These findings illuminate changes important for a mechanistic understanding of the virus, and support continuing surveillance of Spike mutations to aid in the development of immunological interventions.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            mRNA vaccines — a new era in vaccinology

            mRNA vaccines represent a promising alternative to conventional vaccine approaches because of their high potency, capacity for rapid development and potential for low-cost manufacture and safe administration. However, their application has until recently been restricted by the instability and inefficient in vivo delivery of mRNA. Recent technological advances have now largely overcome these issues, and multiple mRNA vaccine platforms against infectious diseases and several types of cancer have demonstrated encouraging results in both animal models and humans. This Review provides a detailed overview of mRNA vaccines and considers future directions and challenges in advancing this promising vaccine platform to widespread therapeutic use.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              SARS-CoV-2 mRNA Vaccine Design Enabled by Prototype Pathogen Preparedness

              Summary A severe acute respiratory syndrome coronavirus (SARS-CoV-2) vaccine is needed to control the global coronavirus infectious disease (COVID-19) public health crisis. Atomic-level structures directed the application of prefusion-stabilizing mutations that improved expression and immunogenicity of betacoronavirus spike proteins 1 . Using this established immunogen design, the release of SARS-CoV-2 sequences triggered immediate rapid manufacturing of an mRNA vaccine expressing the prefusion-stabilized SARS-CoV-2 spike trimer (mRNA-1273). Here, we show that mRNA-1273 induces both potent neutralizing antibody responses to wild-type (D614) and D614G mutant 2 SARS-CoV-2 and CD8 T cell responses and protects against SARS-CoV-2 infection in lungs and noses of mice without evidence of immunopathology. mRNA-1273 is currently in Phase 3 efficacy evaluation.
                Bookmark

                Author and article information

                Journal
                Vaccine
                Vaccine
                Vaccine
                Globe Biotech Limited. Published by Elsevier Ltd.
                0264-410X
                1873-2518
                18 May 2021
                18 May 2021
                Affiliations
                Globe Biotech Ltd., 3/Ka (New), Tejgaon I/A, Dhaka – 1208, Bangladesh
                Author notes
                [* ]Corresponding author.
                Article
                S0264-410X(21)00607-1
                10.1016/j.vaccine.2021.05.035
                8130517
                ef75f86d-941b-4c22-b3a0-bf3b02d63800
                © 2021 Globe Biotech Limited

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

                History
                : 16 January 2021
                : 1 May 2021
                : 12 May 2021
                Categories
                Article

                Infectious disease & Microbiology
                covid,coronavirus,d614g,lipid nanoparticle,lnp,vaccination,immunization
                Infectious disease & Microbiology
                covid, coronavirus, d614g, lipid nanoparticle, lnp, vaccination, immunization

                Comments

                Comment on this article