The Immunological Basis for Immunization Series
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Contrasting Influenza and Respiratory Syncytial Virus
REVIEW published: 02 March 2018 doi: 10.3389/fimmu.2018.00323 Induction and Subversion of Human Protective Immunity: Contrasting influenza and Respiratory Syncytial Virus Stephanie Ascough, Suzanna Paterson and Christopher Chiu* Section of Infectious Diseases and Immunity, Imperial College London, London, United Kingdom Respiratory syncytial virus (RSV) and influenza are among the most important causes of severe respiratory disease worldwide. Despite the clinical need, barriers to devel- oping reliably effective vaccines against these viruses have remained firmly in place for decades. Overcoming these hurdles requires better understanding of human immunity and the strategies by which these pathogens evade it. Although superficially similar, the virology and host response to RSV and influenza are strikingly distinct. Influenza induces robust strain-specific immunity following natural infection, although protection by current vaccines is short-lived. In contrast, even strain-specific protection is incomplete after RSV Edited by: and there are currently no licensed RSV vaccines. Although animal models have been Steven Varga, critical for developing a fundamental understanding of antiviral immunity, extrapolating University of Iowa, United States to human disease has been problematic. It is only with recent translational advances Reviewed by: (such as controlled human infection models and high-dimensional technologies) that the Tara Marlene Strutt, mechanisms responsible for differences in protection against RSV compared to influenza University of Central Florida, have begun to be elucidated in the human context. Influenza infection elicits high-affinity United States Jie Sun, IgA in the respiratory tract and virus-specific IgG, which correlates with protection. Long- Mayo Clinic Minnesota, lived influenza-specific T cells have also been shown to ameliorate disease. -
Puzzling Inefficiency of H5N1 Influenza
Puzzling inefficiency of H5N1 influenza vaccines in Egyptian poultry Jeong-Ki Kima,b, Ghazi Kayalia, David Walkera, Heather L. Forresta, Ali H. Ellebedya, Yolanda S. Griffina, Adam Rubruma, Mahmoud M. Bahgatc, M. A. Kutkatd, M. A. A. Alie, Jerry R. Aldridgea, Nicholas J. Negoveticha, Scott Kraussa, Richard J. Webbya,f, and Robert G. Webstera,f,1 aDivision of Virology, Department of Infectious Diseases, St. Jude Children’s Research Hospital, Memphis, TN 38105; bKorea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Republic of Korea; cDepartment of Infection Genetics, the Helmholtz Center for Infection Research, Inhoffenstrasse 7, D-38124 Braunschweig, Germany; dVeterinary Research Division, and eCenter of Excellence for Advanced Sciences, National Research Center, 12311 Dokki, Giza, Egypt; and fDepartment of Pathology, University of Tennessee Health Science Center, Memphis, TN 38106 Contributed by Robert G. Webster, May 10, 2010 (sent for review March 1, 2010) In Egypt, efforts to control highly pathogenic H5N1 avian influenza virus emulsion H5N1 vaccines imported from China and Europe) virus in poultry and in humans have failed despite increased have failed to provide the expected level of protection against the biosecurity, quarantine, and vaccination at poultry farms. The ongo- currently circulating clade 2.2.1 H5N1 viruses (21). Despite the ing circulation of HP H5N1 avian influenza in Egypt has caused >100 attempted implementation of these measures, the current strat- human infections and remains an unresolved threat to veterinary and egies have limitations (22). public health. Here, we describe that the failure of commercially avail- Antibodies to the circulating virus strain had been detected in able H5 poultry vaccines in Egypt may be caused in part by the passive day-old chicks in Egypt (see below). -
UC Irvine UC Irvine Electronic Theses and Dissertations
UC Irvine UC Irvine Electronic Theses and Dissertations Title Computation Models of Virus Dynamics Permalink https://escholarship.org/uc/item/3zb6480f Author Roy, Sarah M. Publication Date 2015 Peer reviewed|Thesis/dissertation eScholarship.org Powered by the California Digital Library University of California UNIVERSITY OF CALIFORNIA, IRVINE Computational Models of Virus Dynamics DISSERTATION submitted in partial satisfaction of the requirements for the degree of DOCTOR OF PHILOSOPHY in Ecology and Evolutionary Biology by Sarah Marie Roy Dissertation Committee: Professor Dominik Wodarz, Chair Associate Professor Robin Bush Associate Professor Kevin Thornton 2015 © 2015 Sarah Marie Roy DEDICATION To my parents and to Hans, in loving memory ii TABLE OF CONTENTS Page LIST OF FIGURES iv ACKNOWLEDGMENTS v CURRICULUM VITAE vi ABSTRACT OF THE DISSERTATION vii INTRODUCTION 1 CHAPTER 1: Infection of HIV-specific CD4 T helper cells and the clonal 13 composition of the response CHAPTER 2: Tissue architecture, feedback regulation, and resilience to 46 viral infection CHAPTER 3: An Agent-Based Model of HIV Coinfection 71 iii LIST OF FIGURES Page Figure 1.1 Outcomes of model (1) assuming a single helper cell cell clone 21 Figure 1.2 Outcomes of model (2) assuming two independently regulated 24 helper cell clones Figure 1.3 Outcomes of model (2) depending on a and b 26 Figure 1.4 Outcomes of model (2) depending on r1 and r2 27 Figure 1.5 Outcomes of model (4) depending on CTL parameters 33 Figure 2.1 Dependence of Sfrac and Dfrac on replication rate, b 53 Figure 2.2 Tissue architecture and resilience to infection according to 55 model (2) Figure 2.3 Uncontrolled growth in the context of negative feedback 59 according to model (2) Figure 2.4 Two different virus persistence equilibria in the stem cell 61 infection model Figure 2.5 Stem cell infection rate vs. -
Dissecting Human Antibody Responses Against Influenza a Viruses and Antigenic Changes That Facilitate Immune Escape
University of Pennsylvania ScholarlyCommons Publicly Accessible Penn Dissertations 2018 Dissecting Human Antibody Responses Against Influenza A Viruses And Antigenic Changes That Facilitate Immune Escape Seth J. Zost University of Pennsylvania, [email protected] Follow this and additional works at: https://repository.upenn.edu/edissertations Part of the Allergy and Immunology Commons, Immunology and Infectious Disease Commons, Medical Immunology Commons, and the Virology Commons Recommended Citation Zost, Seth J., "Dissecting Human Antibody Responses Against Influenza A Viruses And Antigenic Changes That Facilitate Immune Escape" (2018). Publicly Accessible Penn Dissertations. 3211. https://repository.upenn.edu/edissertations/3211 This paper is posted at ScholarlyCommons. https://repository.upenn.edu/edissertations/3211 For more information, please contact [email protected]. Dissecting Human Antibody Responses Against Influenza A Viruses And Antigenic Changes That Facilitate Immune Escape Abstract Influenza A viruses pose a serious threat to public health, and seasonal circulation of influenza viruses causes substantial morbidity and mortality. Influenza viruses continuously acquire substitutions in the surface glycoproteins hemagglutinin (HA) and neuraminidase (NA). These substitutions prevent the binding of pre-existing antibodies, allowing the virus to escape population immunity in a process known as antigenic drift. Due to antigenic drift, individuals can be repeatedly infected by antigenically distinct influenza strains over the course of their life. Antigenic drift undermines the effectiveness of our seasonal influenza accinesv and our vaccine strains must be updated on an annual basis due to antigenic changes. In order to understand antigenic drift it is essential to know the sites of antibody binding as well as the substitutions that facilitate viral escape from immunity. -
Fitness Costs Limit Influenza a Virus Hemagglutinin Glycosylation
Fitness costs limit influenza A virus hemagglutinin PNAS PLUS glycosylation as an immune evasion strategy Suman R. Dasa,b,1, Scott E. Hensleya,2, Alexandre Davida, Loren Schmidta, James S. Gibbsa, Pere Puigbòc, William L. Incea, Jack R. Benninka, and Jonathan W. Yewdella,3 aLaboratory of Viral Diseases, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD 20892; bEmory Vaccine Center, Emory University, Atlanta, GA 30322; and cNational Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894 AUTHOR SUMMARY Influenza A virus remains an acid substitutions distributed important human pathogen among the four antigenic sites largely because of its ability to recognized by various mono- evade antibodies that neutralize clonal antibodies, indicating viral infectivity. The virus conserved antigenicity among escapes neutralization by alter- the mutants for this mAb (2). ing the target of these anti- Third and highly ironically, bodies, the HA glycoprotein, in escape mutants selected with a process known as antigenic H28-A2 show reduced binding drift. HA attaches the virus to to a remarkably large frac- specific molecules (terminal tion of other monoclonal anti- sialic acid residues) on target bodies (71%) that recognize cells to initiate the infectious one (or a combination) of the cycle. Antibodies that interact four antigenic sites in the glob- with the globular structure ular domain. of the HA protein physically Sequencing of two H28-A2 block virus attachment or the egg-generated escape mutants subsequent HA-mediated (OV1 and OV2) immediately fusion of viral and cellular revealed that their low fre- membranes, thereby neutraliz- quency and high degree of ing viral infectivity. -
Selection of Antigenically Advanced Variants of Seasonal Influenza Viruses
ARTICLES PUBLISHED: 23 MAY 2016 | ARTICLE NUMBER: 16058 | DOI: 10.1038/NMICROBIOL.2016.58 Selection of antigenically advanced variants of seasonal influenza viruses Chengjun Li1†,MasatoHatta1†, David F. Burke2,3†, Jihui Ping1†,YingZhang1†,MakotoOzawa1,4, Andrew S. Taft1, Subash C. Das1, Anthony P. Hanson1, Jiasheng Song1, Masaki Imai1,5, Peter R. Wilker1, Tokiko Watanabe6, Shinji Watanabe6,MutsumiIto7, Kiyoko Iwatsuki-Horimoto7, Colin A. Russell3,8,9, Sarah L. James2,3, Eugene Skepner2,3, Eileen A. Maher1, Gabriele Neumann1, Alexander I. Klimov10‡, Anne Kelso11,JohnMcCauley12,DayanWang13, Yuelong Shu13,TakatoOdagiri14, Masato Tashiro14, Xiyan Xu10,DavidE.Wentworth10, Jacqueline M. Katz10,NancyJ.Cox10, Derek J. Smith2,3,15* and Yoshihiro Kawaoka1,4,6,7* Influenza viruses mutate frequently, necessitating constant updates of vaccine viruses. To establish experimental approaches that may complement the current vaccine strain selection process, we selected antigenic variants from human H1N1 and H3N2 influenza virus libraries possessing random mutations in the globular head of the haemagglutinin protein (which includes the antigenic sites) by incubating them with human and/or ferret convalescent sera to human H1N1 and H3N2 viruses. We also selected antigenic escape variants from human viruses treated with convalescent sera and from mice that had been previously immunized against human influenza viruses. Our pilot studies with past influenza viruses identified escape mutants that were antigenically similar to variants that emerged in nature, establishing the feasibility of our approach. Our studies with contemporary human influenza viruses identified escape mutants before they caused an epidemic in 2014–2015. This approach may aid in the prediction of potential antigenic escape variants and the selection of future vaccine candidates before they become widespread in nature. -
RNA Viruses As Tools in Gene Therapy and Vaccine Development
G C A T T A C G G C A T genes Review RNA Viruses as Tools in Gene Therapy and Vaccine Development Kenneth Lundstrom PanTherapeutics, Rte de Lavaux 49, CH1095 Lutry, Switzerland; [email protected]; Tel.: +41-79-776-6351 Received: 31 January 2019; Accepted: 21 February 2019; Published: 1 March 2019 Abstract: RNA viruses have been subjected to substantial engineering efforts to support gene therapy applications and vaccine development. Typically, retroviruses, lentiviruses, alphaviruses, flaviviruses rhabdoviruses, measles viruses, Newcastle disease viruses, and picornaviruses have been employed as expression vectors for treatment of various diseases including different types of cancers, hemophilia, and infectious diseases. Moreover, vaccination with viral vectors has evaluated immunogenicity against infectious agents and protection against challenges with pathogenic organisms. Several preclinical studies in animal models have confirmed both immune responses and protection against lethal challenges. Similarly, administration of RNA viral vectors in animals implanted with tumor xenografts resulted in tumor regression and prolonged survival, and in some cases complete tumor clearance. Based on preclinical results, clinical trials have been conducted to establish the safety of RNA virus delivery. Moreover, stem cell-based lentiviral therapy provided life-long production of factor VIII potentially generating a cure for hemophilia A. Several clinical trials on cancer patients have generated anti-tumor activity, prolonged survival, and -
Revisiting the Elusive Hepatitis C Vaccine
Editorial Revisiting the Elusive Hepatitis C Vaccine Stephen M. Todryk 1,2,* , Margaret F. Bassendine 2,* and Simon H. Bridge 1,2,* 1 Faculty of Health & Life Sciences, Northumbria University, Newcastle upon Tyne NE1 8ST, UK 2 Translational & Clinical Research Institute, The Medical School, Newcastle University, Newcastle upon Tyne NE2 4HH, UK * Correspondence: [email protected] (S.M.T.); [email protected] (M.F.B.); [email protected] (S.H.B.) The impactful discovery and subsequent characterisation of hepatitis C virus (HCV), an RNA virus of the flavivirus family, led to the awarding of the 2020 Nobel Prize in Physiology or Medicine to Harvey J. Alter, Michael Houghton and Charles M. Rice [1]. However, despite the significant advances recognised by this Nobel prize, an effective HCV vaccine remains elusive. The recent success of vaccines against SARS-CoV-2, developed with unprecedented speed, has shone a bright light on the vaccination process for protection against viral threats and may provide renewed impetus for the development of vaccines for other viruses. HCV infection remains a major global health problem as approximately three quarters of those infected develop chronic infection, leading to morbidity and mortality due to progressive liver fibrosis, cirrhosis and cancer. The World Health Organization (WHO) estimates that 71.1 million people are living with chronic HCV, resulting in over 400,000 deaths every year. In 2016, the WHO adopted a global strategy with the aim of eliminating viral hepatitis as a public health problem, comprising targets to reduce new viral hepatitis infections by 90% and reduce deaths due to viral hepatitis by 65% by 2030. -
Study Toward the Development of Advanced
STUDY TOWARD THE DEVELOPMENT OF ADVANCED INFLUENZA VACCINES DISSERTATION Presented in partial fulfillment of the Requirements for the Degree Doctor of Philosophy in the Graduate School of the Ohio State University By Leyi Wang B.S.,M.S. Graduate Program in Veterinary Preventive Medicine The Ohio State University 2009 Dissertation Committee: Professor Chang-Won Lee, advisor Professor Y.M. Saif, Professor Daral J. Jackwood Professor Jeffrey T. LeJeune Copyright by Leyi Wang 2009 ABSTRACT Avian influenza is one of the most economically important diseases in poultry. Since it was found in Italy in 1878, avian influenza virus has caused numerous outbreaks around the world, resulting in considerable economic losses in poultry industry. In addition to affecting poultry, different subtypes of avian influenza viruses can infect many other species, thus complicating prevention and control. Killed and fowlpox virus vectored HA vaccines have been used in the field as one of effective strategies in a comprehensive control program to prevent and control avian influenza. Live attenuated vaccines for poultry are still under development. Live attenuated vaccines can closely mimic natural infection inducing long-lasting humoral and cellular immunity. In addition, they may be used for mass vaccination. However, concerns with spread of live vaccine viruses, mutation into virulent strains from live attenuated viruses, and reassortment of vaccine and field strains prevent recommending live vaccines as poultry vaccines in the field. For this reason, there are increasing interests in the development of in ovo vaccines that can reduce the risk of spreading the vaccine virus. Therefore, in the first three parts of our study, we have explored several strategies (NS1 truncation, temperature sensitive (ts) mutations, HA substitution, and non-coding region (NCR) mutations) to attenuate viruses to reach this goal. -
Vaccines: Past, Present and Future
HISTORICAL PERSPECTIVE Vaccines: past, present and future Stanley A Plotkin The vaccines developed over the first two hundred years since Jenner’s lifetime have accomplished striking reductions of infection and disease wherever applied. Pasteur’s early approaches to vaccine development, attenuation and inactivation, are even now the two poles of vaccine technology. Today, purification of microbial elements, genetic engineering and improved knowledge of immune protection allow direct creation of attenuated mutants, expression of vaccine proteins in live vectors, purification and even synthesis of microbial antigens, and induction of a variety of immune responses through manipulation of DNA, RNA, proteins and polysaccharides. Both noninfectious and infectious diseases are now within the realm of vaccinology. The profusion of new vaccines enables new populations to be targeted for vaccination, and requires the development of routes of administration additional to injection. With all this come new problems in the production, regulation and distribution of vaccines. http://www.nature.com/naturemedicine “The Circassians [a Middle Eastern people] perceived that of a thou- mild illness in humans, could prevent smallpox. This discovery not sand persons hardly one was attacked twice by full blown smallpox; only led to the eradication of smallpox in the twentieth century, but that in truth one sees three or four mild cases but never two that are also gave cachet to the idea of deliberate protection against exposure serious and dangerous; that in a word one never truly has that illness to infectious diseases. twice in life.” The history of vaccination as a deliberate endeavor began in the Voltaire, “On Variolation,” Philosophical Letters, 1734 laboratory of Louis Pasteur. -
Reported on January 27, 2020
Introduction 3 Executive Summary 5 Chapter 1 Second Round of Survey : Data Analysis 10 Chapter 2 Comparative Analysis (2020 and 2021) 37 Chapter 3 A Discourse on Pandemic Viruses and Vaccines -PVS Kumar 60 Chapter 4 Persisting Socio-economic Crisis: COVID-19 Lays Bare the Social Fault Lines1 - Prof. Arun Kumar 96 Annexure 1 113 Annexure 2 120 Annexure 2a 129 Index 1 The Second Pulse of the Pandemic : A Sudden Surge in Scientic Temper during the Covid-19 Crisis © Anhad 2021 Acknowledgement : PM Bhargava Foundation We are thankful to the following for helping us collect the data : Bhavesh Bariya Bhavna Sharma Deshdeep Dhankar Dev Desai Farida Khan Farhat Khan Jagori Rural Manish Kumar Ray Manisha Trivedi Mukhtar Shaikh Nazneen Shaikh Published by : Printed by : Pullshoppe 9810213737 2 Introduction Scientific community rises to the occasion Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), after mutation, found a new host, the human cell, and comfortably multiplied itself. Used human cells as copying machines and made millions of copies in nasal cavities, throats and lungs at times in human eyes, which could survive in aerosols and various surfaces for more than 72 hours. The human bodies proved to be secured habitable housing colonies, which not only offered environment for its multiplication within the body at an exponential rate but also helped it to travel all over the globe. Within human cells it also mutated, changed in shape and content, and became extra virulent, which made it extremely difficult to suppress or impede its propagation. Evidently, the virus showed no signs of leaving the newfound housing complexes in a hurry. -
Approach to a Highly-Virulent Emerging Viral Epidemic: a Thought Experiment and Literature Review
Approach to a highly-virulent emerging viral epidemic: A thought experiment and literature review 1 2 2 Mohamed Amgad , Yousef A Fouad , Maha AT Elsebaie 1. Department of Biomedical Informatics, Emory University, Atlanta, GA, USA 2. Faculty of Medicine, Ain Shams University, Cairo, Egypt Corresponding Author: Mohamed Amgad1 Email address: [email protected] 1 PeerJ Preprints | https://doi.org/10.7287/peerj.preprints.27518v1 | CC BY 4.0 Open Access | rec: 5 Feb 2019, publ: 5 Feb 2019 Table of contents ____________________________________________________________________________ Abstract 3 Introduction 3 Survey Methodology 4 Thematic analysis 4 1a. Thematic analysis of key findings 4 1b. Potential causes of tissue damage and mortality 5 Table 2: Potential mediators of tissue damage and lethality. 5 1c. Possible viral virulence and immune evasion tactics 6 1d. The peculiar finding of lymphopenia 10 Table 4: Potential mechanisms behind lymphopenia and immune suppression. 10 1e. Why serum is non-protective 11 Table 5: Potential mechanisms why serum is non-protective. 11 2. Interrogation of viral biology 12 2a. Detailed clinical workup 12 2b. In-depth assessment of immune response 13 2c. Determination of virus structure and classification 15 2d. Investigating viral tissue tropism and host binding targets 16 2e. Investigating viral antigenic determinants and natural antibody targets 16 2f. Establishment of in-vitro and in-vivo experimental models 17 3. Management and vaccination strategy 17 3a. Non-vaccine management strategies 17 3b. Dynamics of infection spread and herd immunity threshold 18 3c. Vaccine development strategy 18 3d. Identification of peptide/subunit vaccine candidates 20 3e. Testing vaccine candidates 20 4.