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      The Matrix-M™ adjuvant: A critical component of vaccines for the 21 st century

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          ABSTRACT

          Matrix-M™ adjuvant is a key component of several novel vaccine candidates. The Matrix-M adjuvant consists of two distinct fractions of saponins purified from the Quillaja saponaria Molina tree, combined with cholesterol and phospholipids to form 40-nm open cage-like nanoparticles, achieving potent adjuvanticity with a favorable safety profile. Matrix-M induces early activation of innate immune cells at the injection site and in the draining lymph nodes. This translates into improved magnitude and quality of the antibody response to the antigen, broadened epitope recognition, and the induction of a Th1-dominant immune response. Matrix-M-adjuvanted vaccines have a favorable safety profile and are well tolerated in clinical trials. In this review, we discuss the latest findings on the mechanisms of action, efficacy, and safety of Matrix-M adjuvant and other saponin-based adjuvants, with a focus on the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) subunit vaccine candidate NVX-CoV2373 developed to prevent coronavirus disease 2019 (COVID-19).

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          The NLRP3 inflammasome: molecular activation and regulation to therapeutics

          Karen V. Swanson, Meng Deng, Jenny P.-Y. Ting (2019)
          NLRP3 (NACHT, LRR and PYD domains-containing protein 3) is an intracellular sensor that detects a broad range of microbial motifs, endogenous danger signals and environmental irritants, resulting in the formation and activation of the NLRP3 inflammasome. Assembly of the NLRP3 inflammasome leads to caspase-1-dependent release of the proinflammatory cytokines, IL-1β and IL-18, as well as to gasdermin D-mediated pyroptotic cell death. Recent studies have revealed new regulators of the NLRP3 inflammasome, including new interacting or regulatory proteins, metabolic pathways and a regulatory mitochondrial hub. In this Review, we present the molecular, cell biological and biochemical basis of NLRP3 activation and regulation, and describe how this mechanistic understanding is leading to potential therapeutics that target the NLRP3 inflammasome.
          Article 0 comments Cited 1825 times – based on 0 reviews     Review now
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            Characterization of the receptor-binding domain (RBD) of 2019 novel coronavirus: implication for development of RBD protein as a viral attachment inhibitor and vaccine

            Wanbo Tai, Lei He, Xiujuan Zhang … (2020)
            The outbreak of Coronavirus Disease 2019 (COVID-19) has posed a serious threat to global public health, calling for the development of safe and effective prophylactics and therapeutics against infection of its causative agent, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), also known as 2019 novel coronavirus (2019-nCoV). The CoV spike (S) protein plays the most important roles in viral attachment, fusion and entry, and serves as a target for development of antibodies, entry inhibitors and vaccines. Here, we identified the receptor-binding domain (RBD) in SARS-CoV-2 S protein and found that the RBD protein bound strongly to human and bat angiotensin-converting enzyme 2 (ACE2) receptors. SARS-CoV-2 RBD exhibited significantly higher binding affinity to ACE2 receptor than SARS-CoV RBD and could block the binding and, hence, attachment of SARS-CoV-2 RBD and SARS-CoV RBD to ACE2-expressing cells, thus inhibiting their infection to host cells. SARS-CoV RBD-specific antibodies could cross-react with SARS-CoV-2 RBD protein, and SARS-CoV RBD-induced antisera could cross-neutralize SARS-CoV-2, suggesting the potential to develop SARS-CoV RBD-based vaccines for prevention of SARS-CoV-2 and SARS-CoV infection.
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              Developing Covid-19 Vaccines at Pandemic Speed

              Nicole Lurie, Melanie Saville, Richard Hatchett … (2020)
              Article 0 comments Cited 729 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): Hum Vaccin Immunother
                Journal ID (iso-abbrev): Hum Vaccin Immunother
                Title: Human Vaccines & Immunotherapeutics
                Publisher: Taylor & Francis
                ISSN (Print): 2164-5515
                ISSN (Electronic): 2164-554X
                Publication date (Electronic, pub): 27 April 2023
                Publication date (Electronic, collection): 2023
                Publication date PMC-release: 27 April 2023
                Volume: 19
                Issue: 1
                Electronic Location Identifier: 2189885
                Affiliations
                [a ]Department Product Development, Novavax AB; , Uppsala, Sweden
                [b ]Department Alliance and Project Management, Novavax AB; , Uppsala, Sweden
                [c ]Department Research and Development, Novavax, Inc; , Gaithersburg, MD, USA
                Author notes
                CONTACT Linda Stertman lstertman@ 123456novavax.com Novavax AB; , Kungsgatan 109, Uppsala SE-753 18, Sweden.
                Author information
                https://orcid.org/0000-0002-9350-4317
                Article
                Publisher ID: 2189885
                DOI: 10.1080/21645515.2023.2189885
                PMC ID: 10158541
                PubMed ID: 37113023
                SO-VID: 54bf1be8-a8e8-45fb-a893-6b36a9cc979b
                Copyright © © 2023 Novavax. Published with license by Taylor & Francis Group, LLC.
                License:

                This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License ( http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way. The terms on which this article has been published allow the posting of the Accepted Manuscript in a repository by the author(s) or with their consent.

                History
                Page count
                Figures: 1, Tables: 1, References: 93, Pages: 1
                Categories
                Subject: Review
                Subject: Novel Vaccines – Review

                ScienceOpen disciplines: Molecular medicine
                Keywords: matrix-m™ adjuvant,quillaja saponin,vaccine,immunogenicity,safety,mechanism of action,innate immune response,adaptive immune response,sars-cov-2,covid-19
                Data availability:
                ScienceOpen disciplines: Molecular medicine
                Keywords: matrix-m™ adjuvant, quillaja saponin, vaccine, immunogenicity, safety, mechanism of action, innate immune response, adaptive immune response, sars-cov-2, covid-19

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