DOCSLIB.ORG

Moderna Inc Corporate Analyst Meeting on April 14, 2020 / 12:00PM

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Moderna Inc Corporate Analyst Meeting on April 14, 2020 / 12:00PM Client Id: 77 THOMSON REUTERS STREETEVENTS EDITED TRANSCRIPT MRNA.OQ - Moderna Inc Corporate Analyst Meeting EVENT DATE/TIME: APRIL 14, 2020 / 12:00PM GMT THOMSON REUTERS STREETEVENTS | www.streetevents.com | Contact Us ©2020 Thomson Reuters. All rights reserved. Republication or redistribution of Thomson Reuters content, including by framing or similar means, is prohibited without the prior written consent of Thomson Reuters. 'Thomson Reuters' and the Thomson Reuters logo are registered trademarks of Thomson Reuters and its affiliated companies. Client Id: 77 APRIL 14, 2020 / 12:00PM, MRNA.OQ - Moderna Inc Corporate Analyst Meeting CORPORATE PARTICIPANTS Juan Andres Moderna, Inc. - Chief Technical Operations & Quality Officer Lavina Talukdar Moderna, Inc. - Head of IR Stéphane Bancel Moderna, Inc. - CEO & Director Stephen Hoge Moderna, Inc. - President Tal Zaks Moderna, Inc. - Chief Medical Officer CONFERENCE CALL PARTICIPANTS Alec Warren Stranahan BofA Merrill Lynch, Research Division - Associate Cory William Kasimov JP Morgan Chase & Co, Research Division - Senior Biotechnology Analyst Edward Andrew Tenthoff Piper Sandler & Co., Research Division - MD & Senior Research Analyst Geoffrey Craig Porges SVB Leerink LLC, Research Division - Director of Therapeutics Research, MD & Senior Biotechnology Analyst Hartaj Singh Oppenheimer & Co. Inc., Research Division - Research Analyst Maxwell Nathan Skor Morgan Stanley, Research Division - Research Associate Salveen Jaswal Richter Goldman Sachs Group Inc., Research Division - VP Umer Raffat Evercore ISI Institutional Equities, Research Division - Senior MD & Senior Analyst of Equity Research Yasmeen Rahimi Roth Capital Partners, LLC, Research Division - MD, Senior Research Analyst & Co-Head of Biotechnology Research Andrew Lo Flor Munoz-Rivas Kathryn Edwards Mark Denison Mark R. Denison Paul Heath PRESENTATION Operator Good morning, and welcome to Moderna's Virtual Vaccine Day. (Operator Instructions) Please be advised that this call is being recorded. At this time, I'd like to turn the call over to Lavina Talukdar, Head of Investor Relations at Moderna. Please proceed. Lavina Talukdar - Moderna, Inc. - Head of IR Thank you, operator, and good morning, everyone. I hope you are all healthy and safe. Thank you for joining Moderna's First Vaccine Day webcast. During the presentations today, you will hear from members of Moderna's executive team and from key opinion leaders in the industry. You can access the press release and the slides accompanying each of the speakers' presentations by going to the Investors section of our website. Before we begin, I'd like to remind everyone that this presentation will include forward-looking statements. Please see Slide 2 of the presentation and our SEC filings for important risk factors that could cause our actual performance and results to differ materially from those expressed or implied in 2 THOMSON REUTERS STREETEVENTS | www.streetevents.com | Contact Us ©2020 Thomson Reuters. All rights reserved. Republication or redistribution of Thomson Reuters content, including by framing or similar means, is prohibited without the prior written consent of Thomson Reuters. 'Thomson Reuters' and the Thomson Reuters logo are registered trademarks of Thomson Reuters and its affiliated companies. Client Id: 77 APRIL 14, 2020 / 12:00PM, MRNA.OQ - Moderna Inc Corporate Analyst Meeting these forward-looking statements. We undertake no obligation to update or revise the information provided during this presentation as a result of new information or future results or developments. With that, I would like to hand it over to Stéphane Bancel, CEO of Moderna. Stéphane Bancel - Moderna, Inc. - CEO & Director Thank you, Lavina. Good morning, and good afternoon, everybody. I hope you and you loved ones are safe. Welcome to Modena's First Vaccine Day. Thank you for joining us today. Given 80% of vaccine worldwide sales are in big 4 pharmaceutical company, back in November, when we announced Vaccine Day, we thought it was important to provide our stakeholders an opportunity to appreciate 3 things about our vaccines. First, that there are still an important number of innovative vaccines that need to be developed that the world needs. Second, the high probability of technical success of infectious disease vaccine caused positive Phase I data as they enter Phase II, which (inaudible) [is over for a particular] area. And third, the totality of Moderna vaccine platform clinical data and where we're excited about the opportunity to impact public health. Obviously, a lot of things have changed since November. So let me turn to the agenda on Slide 3. After a quick introduction, I will turn over to Professor Andrew Lo from MIT, who we introduced at that time. Then Dr. Paul Health is going to review traditional vaccines. Before Stephen Hoge is going to talk about what differentiates mRNA vaccines versus other technologies. Then we plan for a small coffee break before returning where Tal is going to review basically vaccines that we have against infections from mother to baby. i.e. CMV and Zika. And then we're going to review our vaccines against respiratory diseases, which, of course, is extremely important. So Tal will start, and then we'll be happy to welcome Dr. Munoz-Rivas from Baylor College of Medicine. And then we will go to Dr. Mark Denison from Vanderbilt University and then Tal and Juan will close that session. Before my conclusion, we'll have Dr. Kathryn Edwards with an overview with us some overview on ACIP, which is an important framework in the vaccine world, as you all know. And of course, at the end, we'll be very happy to take Q&A. So on Slide 4, as you know, we started the company on the central dogma of biology, believing that mRNA is a software of life and if we could find a way to create medicines out of mRNA, we could have a profound impact on patients. On Slide 4, you see the 4 value drivers that have energized us since the very first days. An opportunity to create a lot of products that are first-in-class products because of their ability to do transmembrane protein, to do intracellular protein or to do combinations of protein. We believe the high probability of technical success of this modality because mRNA is an information molecule. And we use as raw material, either human DNA information or DNA or viruses -- sorry, DNA, RNA or viruses. The third piece was, of course, speed and the ability, again, because of a platform because mRNA is an information molecule to move very quickly in the labs and to move very quickly into clinical research. And fourth was the very interesting aspect of a technology that provide capital efficiency, which I'll come back in a few minutes. And because of this opportunity on Slide 6, to create a new class of medicine, as many of you know, we have been and to this day, are very focused on managing the risk: technology risk, biology risk, execution risk and financing risk. And on Slide 7, you are all familiar with these metrics that we have been using to kind of guide our decision-making as we build the portfolio. Since the beginning, we thought that taking 1 drug to the clinic and hoping that we have figured out everything, was not very wise and was actually extremely risky and could actually jeopardize our mission to use this technology to help patients. And so we decided to try several technology in parallel into the clinic, which you see here on the X axis. And for each of our application and modalities, we decided to diversify our biology risk by going after several drugs in each application, so that we will not take all our risks on only 1 biology assumptions. 3 THOMSON REUTERS STREETEVENTS | www.streetevents.com | Contact Us ©2020 Thomson Reuters. All rights reserved. Republication or redistribution of Thomson Reuters content, including by framing or similar means, is prohibited without the prior written consent of Thomson Reuters. 'Thomson Reuters' and the Thomson Reuters logo are registered trademarks of Thomson Reuters and its affiliated companies. Client Id: 77 APRIL 14, 2020 / 12:00PM, MRNA.OQ - Moderna Inc Corporate Analyst Meeting On Slide 8, as you recall, we believe that 2019 is a very important inflection year in the company's history. Because as we said the strategy to led the clinical data guide us from where the technology is working best, we have very critical clinical data in 2019. With CMV, we had of 6 clinical data sets around our infectious disease vaccine, which gave us, of course, strong conviction that we believe the prophylactic vaccine modality has been de-risked. And at the same time, we shared new data on our systemic secreted and cell surface therapeutics were chikungunya antibody data in the fall. So if you think about the company moving forward on Slide 9, this is how we think about the company, exactly in line with our strategy, which is because the clinical data have informed us that prophylactic vaccine and systemic secreted and cell surface therapeutics have been de-risked, we have named those 2 modalities core modalities, where according to our strategy, which were about years and years ago, we want now to double down and to enable many more important medicines to get to the clinic and hopefully, to get to the market to help people. On the right side of the slide, the exploratory modality is a set of programs that are in the clinic for the personalized cancer vaccine, the KRAS cancer vaccine. We have 3 immuno-oncology assets in intratumoral immuno-oncology: the triplet, OX40L + IL23 + IL36y, OX40 and also IL-12, which is partnered with AstraZeneca. The VEGF program in Phase II. And for MMA and PA, we have 2 open INDs and 2 products that the FDA has fast tracked.
Load more

Recommended publications
  • Modelling Immunization Strategies with Cytomegalovirus Vaccine Candidates
    Epidemiol. Infect. (2011), 139, 1818–1826. f Cambridge University Press 2011 doi:10.1017/S0950268811000343 Modelling immunization strategies with cytomegalovirus vaccine candidates R.S. AZEVEDO1* AND M. AMAKU2 1 Departamento de Patologia & LIM 01 HC, Faculdade de Medicina, Universidade de Sa˜o Paulo, Brazil 2 Departamento de Medicina Veterina´ria Preventiva e Sau´de Animal, Faculdade de Medicina Veterina´ria e Zootecnia, Universidade de Sa˜o Paulo, Brazil (Accepted 16 February 2011; first published online 14 March 2011) SUMMARY In order to analyse the impact of vaccination against cytomegalovirus (CMV) on congenital infection incidence using current vaccines tested in phase II clinical trials, we simulated different scenarios by mathematical modelling, departing from the current vaccine characteristics, varying age at vaccination, immunity waning, vaccine efficacy and mixing patterns. Our results indicated that the optimal age for a single vaccination interval is from 2 to 6 months if there is no immunity waning. Congenital infection may increase if vaccine-induced immunity wanes before 20 years. Congenital disease should increase further when the mixing pattern includes transmission among children with a short duration of protection vaccine. Thus, the best vaccination strategy is a combined schedule: before age 1 year plus a second dose at 10–11 years. For CMV vaccines with low efficacy, such as the current ones, universal vaccination against CMV should be considered for infants and teenagers. Key words: Cytomegalovirus vaccine, immunity waning, immunization strategies, modelling. INTRODUCTION adolescence, when seroprevalence increases again [1, 2]. These observations suggest that the force of Cytomegalovirus (CMV) infection may be the cause of infection, defined as the per capita rate at which mental retardation and deafness in newborns, infec- susceptible individuals acquire infection, may be re- tious mononucleosis syndrome in young adults, and presented by a bimodal pattern.
    [Show full text]
  • Trends in Vaccine Availability and Novel Vaccine Delivery Technologies: 2008–2025
    Landscape Analysis Trends in vaccine availability and novel vaccine delivery technologies: 2008–2025 July 2008 Bâtiment Avant Centre Phone: 33.450.28.00.49 13 Chemin du Levant Fax: 33.450.28.04.07 01210 Ferney Voltaire www.path.org France www.who.int Landscape Analysis Trends in vaccine availability and novel vaccine delivery technologies: 2008–2025 July 1, 2008 Version: January 22, 2009 ii Table of contents Acronyms and abbreviations.......................................................................................................................................... iv Executive summary......................................................................................................................................................... 1 TRENDS IN VACCINE AVAILABILITY: 2008–2025 ............................................................................................. 2 Choice of vaccine types to be surveyed........................................................................................................................... 2 Vaccine availability and use: 2008–2025........................................................................................................................ 2 Vaccine availability............................................................................................................................................... 2 Delivery strategies................................................................................................................................................. 4 Extensions
    [Show full text]
  • Download Full .Pdf
    Seminars in Immunology xxx (xxxx) xxx Contents lists available at ScienceDirect Seminars in Immunology journal homepage: www.elsevier.com/locate/ysmim Review New viral vectors for infectious diseases and cancer Emanuele Sasso a,b,1, Anna Morena D’Alise a,1, Nicola Zambrano b,c, Elisa Scarselli a, Antonella Folgori d, Alfredo Nicosia b,c,* a Nouscom srl, Via di Castel Romano 100, 00128 Rome, Italy b Ceinge-Biotecnologie Avanzate S.C. A.R.L., via Gaetano Salvatore 486, 80145 Naples, Italy c Department of Molecular Medicine and Medical Biotechnology, University Federico II, Via Pansini 5, 80131 Naples, Italy d Reithera Srl, Via Castel Romano 100, 00128 Rome, Italy ARTICLE INFO ABSTRACT Keywords: Since the discovery in 1796 by Edward Jenner of vaccinia virus as a way to prevent and finally eradicate Genetic vaccine smallpox, the concept of using a virus to fight another virus has evolved into the current approaches of viral Viral vector vectored genetic vaccines. In recent years, key improvements to the vaccinia virus leading to a safer version Cancer vaccine (Modified Vaccinia Ankara, MVA) and the discovery that some viruses can be used as carriers of heterologous Oncolytic virus genes encoding for pathological antigens of other infectious agents (the concept of ‘viral vectors’) has spurred a Poxvirus Adenovirus new wave of clinical research potentially providing for a solution for the long sought after vaccines against major Rhabdovirus diseases such as HIV, TB, RSV and Malaria, or emerging infectious diseases including those caused by filoviruses Paramixovirus and coronaviruses. The unique ability of some of these viral vectors to stimulate the cellular arm of the immune Arenavirus response and, most importantly, T lymphocytes with cell killing activity, has also reawakened the interest toward Herpesvirus developing therapeutic vaccines against chronic infectious diseases and cancer.
    [Show full text]
  • Development of a Vaccine Against Human Cytomegalovirus: Advances, Barriers, and Implications for the Clinical Practice
    Review Development of a Vaccine against Human Cytomegalovirus: Advances, Barriers, and Implications for the Clinical Practice Sara Scarpini 1, Francesca Morigi 1, Ludovica Betti 1, Arianna Dondi 2,* , Carlotta Biagi 2 and Marcello Lanari 2 1 Specialty School of Pediatrics, Alma Mater Studiorum, University of Bologna, 40126 Bologna, Italy; [email protected] (S.S.); [email protected] (F.M.); [email protected] (L.B.) 2 Pediatric Emergency Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy; [email protected] (C.B.); [email protected] (M.L.) * Correspondence: [email protected] Abstract: Human cytomegalovirus (hCMV) is one of the most common causes of congenital infection in the post-rubella era, representing a major public health concern. Although most cases are asymp- tomatic in the neonatal period, congenital CMV (cCMV) disease can result in permanent impairment of cognitive development and represents the leading cause of non-genetic sensorineural hearing loss. Moreover, even if hCMV mostly causes asymptomatic or pauci-symptomatic infections in immunocompetent hosts, it may lead to severe and life-threatening disease in immunocompromised patients. Since immunity reduces the severity of disease, in the last years, the development of an effective and safe hCMV vaccine has been of great interest to pharmacologic researchers. Both hCMV live vaccines—e.g., live-attenuated, chimeric, viral-based—and non-living ones—subunit, RNA-based, virus-like particles, plasmid-based DNA—have been investigated. Encouraging data are emerging from clinical trials, but a hCMV vaccine has not been licensed yet. Major difficulties in Citation: Scarpini, S.; Morigi, F.; the development of a satisfactory vaccine include hCMV’s capacity to evade the immune response, Betti, L.; Dondi, A.; Biagi, C.; Lanari, M.
    [Show full text]
  • Artículos Científicos
    Editor: NOEL GONZÁLEZ GOTERA Número 112 Diseño: Lic. Roberto Chávez y Liuder Machado. Semana 301113 – 061213 Foto: Lic. Belkis Romeu e Instituto Finlay La Habana, Cuba. ARTÍCULOS CIENTÍFICOS Publicaciones incluidas en PubMED durante el período comprendido entre el 29 de noviembre y el 6 de diciembre de 2013. Con “vaccin*” en título: 115 artículos recuperados. Vacunas Meningococo (Neisseria meningitidis) 35. [A new preventio strategy against meningococcal disease: the menigococcus B vaccine]. Gil De Miguel A. An R Acad Nac Med (Madr). 2012;129(1):267-74; discussion 275-7. Spanish. PMID: 24294728 [PubMed - in process] Related citations Select item 24294248 106. Modelled evaluation of multi-component meningococcal vaccine (Bexsero®) for the prevention of invasive meningococcal disease in infants and adolescents in the UK. Huels J, Clements KM, McGarry LJ, Hill GJ, Wassil J, Kessabi S. Epidemiol Infect. 2013 Nov 28:1-13. [Epub ahead of print] PMID: 24284038 [PubMed - as supplied by publisher] Related citations Select item 24283990 Vacunas BCG – ONCO BCG (Mycobacterium bovis) 1 1. Paratuberculosis vaccination causes only limited cross-reactivity in the skin test for diagnosis of bovine tuberculosis. Garrido JM, Vazquez P, Molina E, Plazaola JM, Sevilla IA, Geijo MV, Alonso-Hearn M, Juste RA. PLoS One. 2013 Nov 26;8(11):e80985. doi: 10.1371/journal.pone.0080985. PMID: 24303029 [PubMed - in process] Related citations Select item 24302925 36. Bovine response to lipoarabinomannan vaccination and challenge with Mycobacterium paratuberculosis. Jolly A, Morsella C, Bass L, Fiorentino MA, Paolicchi FA, Mundo SL. Braz J Microbiol. 2013 Oct 30;44(2):511-4. doi: 10.1590/S1517-83822013000200029.
    [Show full text]
  • Recombinant Cytomegalovirus Glycoprotein B Vaccine: Rethinking the Immunological Basis of Protection Mark R
    COMMENTARY COMMENTARY Recombinant cytomegalovirus glycoprotein B vaccine: Rethinking the immunological basis of protection Mark R. Schleissa,1 Development and licensure of a vaccine against hu- is a subunit vaccine based on the viral envelope glyco- man CMV infection is a major public health priority. protein B (gB; gpUL55). Two important papers published Although the major driving force for a CMV vaccine is in PNAS (3, 4) provide surprising and novel insights into prevention of congenital infection—since CMV is the the protecting mechanisms conferred by this gB vaccine. most common viral cause of permanent neurodevelop- How did the CMV gB emerge as a leading vaccine mental disability in infants globally (1)—other patient candidate? CMV gB is a type 1 envelope glycoprotein populations, in particular recipients of hematopoietic and class III viral fusogen (5). It is synthesized as a 906- or stem cells and solid organ transplant (SOT) patients, could 907-aa polypeptide (depending upon the strain of CMV) benefit from a vaccine. A number of CMV vaccines have that undergoes extensive posttranslational modification, been evaluated in clinical trials in recent years (2). These including glycosylation at N-andO-linked sites, followed have included live, attenuated vaccines; vectored vac- by cleavage by the ubiquitous cellular endoprotease, cines expressing CMV-encoded immunogens; and puri- furin, into amino (gp90)- and carboxy (gp58)-terminal fied recombinant protein vaccines coadministered with moieties (refs. 6 and 7 and Fig. 1). The gp90 and adjuvant. The most extensively studied vaccine to date gp58 subunits are covalently connected by disulfide bonds and the mature, glycosylated gB assumes a tri- meric configuration; the trimer subsequently dimerizes AD-4 AD-4 as the protein assumes its final envelope conformation (8).
    [Show full text]
  • The Jordan Report 20Th Anniversary: Accelerated Development Of
    USA ES IC V R E S N A M U H & D H H E T P L A A R E T H M F F E N O T Accelerated Development of Vaccines Preface In 1982, the National Institute of Allergy and Infectious Dis­ Along with these technological advances, there has been a eases (NIAID) established the Program for the Accelerated heightened awareness of the importance of vaccines for global Development of Vaccines. For 20 years, this program has helped health and security. Acquired immunodeficiency syndrome stimulate the energy, intellect, and ability of scientists in micro­ (AIDS), malaria, and tuberculosis have demonstrated to the biology, immunology, and infectious diseases. Vaccine research world the importance of public health in economic development. has certainly benefited. The status report reflecting this Most recently, the threat of bioterrorism has reminded many progress in vaccine research has come to be known as the Jor­ Americans of the value of vaccines as public health tools. dan Report in recognition of Dr. William Jordan, past director of NIAID’s Division of Microbiology and Infectious Diseases Articles by outside experts in this edition highlight many of the (DMID) and the program’s earliest advocate. scientific advances, challenges, and issues of vaccine research during these two decades. As we look to the decade ahead, the This anniversary edition of the Jordan Report summarizes 20 payoffs from basic research will continue to invigorate vaccine years of achievements in vaccine research driven by the explo­ development, but economic, risk communication, and safety sive technological advances in genomics, immunology, and challenges are likely to influence the licensing of new vaccines.
    [Show full text]
  • Open NS Final Dissertation.Pdf
    The Pennsylvania State University The Graduate School HUMAN CYTOMEGALOVIRUS UTILIZES ESCRT-III AND EXTRACELLULAR VESICLES TO ENHANCE VIRUS SPREAD A Dissertation in Biomedical Sciences by Nicholas T. Streck © 2020 Nicholas T. Streck Submitted in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy August 2020 The dissertation for Nicholas Streck was reviewed and approved by the following: Nicholas J. Buchkovich Assistant Professor of Microbiology and Immunology Penn State Cancer Institute Dissertation Advisor Chair of Committee John W. Wills Distinguished Professor Emeritus of Microbiology and Immunology Jeffery T. Sample Professor of Microbiology and Immunology Penn State Cancer Institute Neil D. Christensen Professor of Pathology and Laboratory Medicine Microbiology and Immunology Penn State Cancer Institute Hui-ling Chiang Professor of Cellular and Molecular Physiology Ralph L. Keil Associate Professor of Biochemistry and Molecular Biology Chair of Biomedical Sciences Graduate Program ii Abstract Human cytomegalovirus (HCMV) is a highly prevalent human pathogen that can cause disease in the developing fetus and immunocompromised patients. A better understanding of the replication cycle of the virus may lead to better therapeutic targets to help control infection. During HCMV infection, cellular membrane from vesicles and organelles localize to a perinuclear region within the cell, which is termed the cytoplasmic viral assembly compartment (cVAC). This is the site of envelopment of progeny virions. Both viral and cellular proteins have been suggested to be involved during this process, but the mechanism of HCMV envelopment within the cVAC remains unknown. Many enveloped viruses utilize the endosomal sorting complexes required for transport (ESCRT) proteins for viral budding and envelopment.
    [Show full text]
  • Tuberculosis Mycobacterium Vector Protects Against a Novel Murine
    A Novel Murine Cytomegalovirus Vaccine Vector Protects against Mycobacterium tuberculosis This information is current as Peter C. L. Beverley, Zsolt Ruzsics, Ariann Hey, Claire of September 29, 2021. Hutchings, Simone Boos, Beatrice Bolinger, Emanuele Marchi, Geraldine O'Hara, Paul Klenerman, Ulrich H. Koszinowski and Elma Z. Tchilian J Immunol 2014; 193:2306-2316; Prepublished online 28 July 2014; Downloaded from doi: 10.4049/jimmunol.1302523 http://www.jimmunol.org/content/193/5/2306 Supplementary http://www.jimmunol.org/content/suppl/2014/07/26/jimmunol.130252 http://www.jimmunol.org/ Material 3.DCSupplemental References This article cites 61 articles, 26 of which you can access for free at: http://www.jimmunol.org/content/193/5/2306.full#ref-list-1 Why The JI? Submit online. by guest on September 29, 2021 • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2014 The Authors All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology A Novel Murine Cytomegalovirus Vaccine Vector Protects against Mycobacterium tuberculosis Peter C.
    [Show full text]
  • Limited Available Evidence Supports Theoretical Predictions of Reduced Vaccine Efficacy at Higher Exposure Dose
    W&M ScholarWorks VIMS Articles Virginia Institute of Marine Science 3-1-2019 Limited available evidence supports theoretical predictions of reduced vaccine efficacy at higher exposure dose Kate E. Langwig M. Gabriela M Gomes Mercedes D Clark Molly Kwitny Steffany Yamada See next page for additional authors Follow this and additional works at: https://scholarworks.wm.edu/vimsarticles Part of the Allergy and Immunology Commons, and the Infectious Disease Commons Recommended Citation Langwig, Kate E.; Gomes, M. Gabriela M; Clark, Mercedes D; Kwitny, Molly; Yamada, Steffany; Wargo, Andrew R.; and Lipsitch, Marc, "Limited available evidence supports theoretical predictions of reduced vaccine efficacy at higher exposure dose" (2019). VIMS Articles. 1222. https://scholarworks.wm.edu/vimsarticles/1222 This Article is brought to you for free and open access by the Virginia Institute of Marine Science at W&M ScholarWorks. It has been accepted for inclusion in VIMS Articles by an authorized administrator of W&M ScholarWorks. For more information, please contact [email protected]. Authors Kate E. Langwig, M. Gabriela M Gomes, Mercedes D Clark, Molly Kwitny, Steffany Yamada, Andrew R. Wargo, and Marc Lipsitch This article is available at W&M ScholarWorks: https://scholarworks.wm.edu/vimsarticles/1222 www.nature.com/scientificreports OPEN Limited available evidence supports theoretical predictions of reduced vaccine efcacy at higher exposure Received: 1 August 2018 Accepted: 30 January 2019 dose Published: xx xx xxxx Kate E. Langwig 1,2, M. Gabriela M. Gomes3,4, Mercedes D. Clark1, Molly Kwitny1, Stefany Yamada1, Andrew R. Wargo5 & Marc Lipsitch 2 Understanding the causes of vaccine failure is important for predicting disease dynamics in vaccinated populations and planning disease interventions.
    [Show full text]
  • Structure of HCMV Glycoprotein B in the Postfusion Conformation Bound to a Neutralizing Human Antibody
    ARTICLE Received 18 Mar 2015 | Accepted 27 Jul 2015 | Published 14 Sep 2015 DOI: 10.1038/ncomms9176 OPEN Structure of HCMV glycoprotein B in the postfusion conformation bound to a neutralizing human antibody Sumana Chandramouli1, Claudio Ciferri1,w, Pavel A. Nikitin2, Stefano Calo´3, Rachel Gerrein1, Kara Balabanis1, James Monroe1, Christy Hebner2, Anders E. Lilja1,w, Ethan C. Settembre4 & Andrea Carfi1 Human cytomegalovirus (HCMV) poses a significant threat to immunocompromised individuals and neonates infected in utero. Glycoprotein B (gB), the herpesvirus fusion protein, is a target for neutralizing antibodies and a vaccine candidate due to its indispensable role in infection. Here we show the crystal structure of the HCMV gB ectodomain bound to the Fab fragment of 1G2, a neutralizing human monoclonal antibody isolated from a seropositive subject. The gB/1G2 interaction is dominated by aromatic residues in the 1G2 heavy chain CDR3 protruding into a hydrophobic cleft in the gB antigenic domain 5 (AD-5). Structural analysis and comparison with HSV gB suggest the location of additional neutralizing antibody binding sites on HCMV gB. Finally, immunoprecipitation experiments reveal that 1G2 can bind to HCMV virion gB suggesting that its epitope is exposed and accessible on the virus surface. Our data will support the development of vaccines and therapeutic antibodies against HCMV infection. 1 GSK Vaccines, 45 Sidney Street, Cambridge, Massachusetts 02139, USA. 2 Novartis Institutes for Biomedical Research, Emeryville, California 94608, USA. 3 GSK Vaccines, Via Fiorentina 1, Siena 53100, Italy. 4 Novartis Influenza Vaccines, 45 Sidney Street, Cambridge, Massachusetts 02139, USA. w Present addresses: Department of Structural Biology, Genentech Inc., 94080 South San Francisco, California, USA (C.C.); Hookipa Biotech AG, 1030 Vienna, Austria (A.E.L.).
    [Show full text]
  • The Immunological Basis for Immunization Series
    The Immunological Basis for Immunization Series Module 5: Tuberculosis Update 2021 The Immunological Basis for Immunization Series Module 5: Tuberculosis Update 2021 The immunological basis for immunization series. Module 5: tuberculosis. Update 2021 (Immunological basis for immunization series; module 5) ISBN 978-92-4-002193-8 (electronic version) ISBN 978-92-4-002194-5 (print version) © World Health Organization 2021 Some rights reserved. This work is available under the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 IGO licence (CC BY-NC-SA 3.0 IGO; https://creativecommons.org/licenses/by-nc-sa/3.0/igo). Under the terms of this licence, you may copy, redistribute and adapt the work for non-commercial purposes, provided the work is appropriately cited, as indicated below. In any use of this work, there should be no suggestion that WHO endorses any specific organization, products or services. The use of the WHO logo is not permitted. If you adapt the work, then you must license your work under the same or equivalent Creative Commons licence. If you create a translation of this work, you should add the following disclaimer along with the suggested citation: “This translation was not created by the World Health Organization (WHO). WHO is not responsible for the content or accuracy of this translation. The original English edition shall be the binding and authentic edition”. Any mediation relating to disputes arising under the licence shall be conducted in accordance with the mediation rules of the World Intellectual Property Organization. Suggested citation. The immunological basis for immunization series. Module 5: tuberculosis. Update 2021.
    [Show full text]