Vaccines for the Twenty-First Century Society
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Vaccination with Recombinant Aspartic Hemoglobinase Reduces Parasitic Load and Blood Loss After Hookworm Infection in Dogs
Open access, freely available online PLoS MEDICINE Vaccination with Recombinant Aspartic Hemoglobinase Reduces Parasite Load and Blood Loss after Hookworm Infection in Dogs Alex Loukas1*, Jeffrey M. Bethony2, Susana Mendez2, Ricardo T. Fujiwara2, Gaddam Narsa Goud2, Najju Ranjit1, Bin Zhan2, Karen Jones2, Maria Elena Bottazzi2, Peter J. Hotez2* 1 Division of Infectious Diseases and Immunology, Queensland Institute of Medical Research, Brisbane, Queensland, Australia, 2 Department of Microbiology and Tropical Medicine, The George Washington University Medical Center, Washington, District of Columbia, United States of America Competing Interests: The authors have declared that no competing ABSTRACT interests exist. Background Author Contributions: AL, JMB, MEB, and PJH designed the study. Hookworms infect 730 million people in developing countries where they are a leading cause AL, RTF, GNG, NR, BZ, performed of intestinal blood loss and iron-deficiency anemia. At the site of attachment to the host, adult experiments. AL, PJH, JMB, SM, and hookworms ingest blood and lyse the erythrocytes to release hemoglobin. The parasites KJ analyzed the data. AL, PJH, JMB, and SM contributed to writing the subsequently digest hemoglobin in their intestines using a cascade of proteolysis that begins paper. with the Ancylostoma caninum aspartic protease 1, APR-1. Academic Editor: Maria Yazdanbakhsh, Leiden University Methods and Findings Medical Center, the Netherlands Citation: Loukas A, Bethony JM, We show that vaccination of dogs with recombinant Ac-APR-1 induced antibody and cellular Mendez S, Fujiwara RT, Goud GN, et responses and resulted in significantly reduced hookworm burdens (p ¼ 0.056) and fecal egg al. (2005) Vaccination with counts (p ¼ 0.018) in vaccinated dogs compared to control dogs after challenge with infective recombinant aspartic hemoglobinase reduces parasite larvae of A. -
Pichia Pastoris (Komagataella Phaffii) As a Cost-Effective Tool for Vaccine
bioengineering Review Pichia pastoris (Komagataella phaffii) as a Cost-Effective Tool for Vaccine Production for Low- and Middle-Income Countries (LMICs) Salomé de Sá Magalhães and Eli Keshavarz-Moore * Department of Biochemical Engineering, University College London, Gower Street, London WC1E 6BT, UK; [email protected] * Correspondence: [email protected] Abstract: Vaccination is of paramount importance to global health. With the advent of the more recent pandemics, the urgency to expand the range has become even more evident. However, the potential limited availability and affordability of vaccines to resource low- and middle-income countries has created a need for solutions that will ensure cost-effective vaccine production methods for these countries. Pichia pastoris (P. pastoris) (also known as Komagataella phaffii) is one of the most promising candidates for expression of heterologous proteins in vaccines development. It combines the speed and ease of highly efficient prokaryotic platforms with some key capabilities of mammalian systems, potentially reducing manufacturing costs. This review will examine the latest developments in P. pastoris from cell engineering and design to industrial production systems with focus on vaccine development and with reference to specific key case studies. Keywords: vaccines; LMICs; expression platforms; P. pastoris (Komagataella phaffii) Citation: de Sá Magalhães, S.; Keshavarz-Moore, E. Pichia pastoris (Komagataella phaffii) as a Cost-Effective 1. Introduction Tool for Vaccine Production for Low- and Middle-Income Countries (LMICs). Infectious diseases have a significant global economic and societal impact. As a result, Bioengineering 2021, 8, 119. https:// during the last two centuries, we have witnessed the remarkable success of vaccination doi.org/10.3390/bioengineering8090119 reducing the burden of infectious diseases [1]. -
Artículos Científicos
Editor: NOEL GONZÁLEZ GOTERA Número 086 Diseño: Lic. Roberto Chávez y Liuder Machado. Semana 010613 - 070613 Foto: Lic. Belkis Romeu e Instituto Finlay La Habana, Cuba. ARTÍCULOS CIENTÍFICOS Publicaciones incluidas en PubMED durante el período comprendido entre el el 1 y el 7 de junio de 2013. Con “vaccin*” en título: 131 artículos recuperados. Vacunas Neumococo (Streptococcus pneumoniae) 98. Is there an authentic increased risk of pneumococcal pneumonia among young mothers whose children were fully vaccinated with PCV7? The role of methodological shortcomings. Castiglia P, Piana A, Sotgiu G. Vaccine. 2013 May 29. doi:pii: S0264-410X(13)00655-5. 10.1016/j.vaccine.2013.05.055. [Epub ahead of print] No abstract available. PMID: 23727001 [PubMed - as supplied by publisher] Related citations Select item 23726847 121. Clonal Expansion within Pneumococcal Serotype 6C after Use of Seven-Valent Vaccine. Loman NJ, Gladstone RA, Constantinidou C, Tocheva AS, Jefferies JM, Faust SN, O'Connor L, Chan J, Pallen MJ, Clarke SC. PLoS One. 2013 May 28;8(5):e64731. doi: 10.1371/journal.pone.0064731. Print 2013. PMID: 23724086 [PubMed - in process] Free Article Related citations Select item 23724021 1 Vacuna Tosferina (Bordetella pertussis) 108. [Pertussis in fully vaccinated infants and children. Are new vaccination strategies required?] Moraga-Llop FA, Mendoza-Palomar N, Muntaner-Alonso A, Codina-Grau G, Fàbregas-Martori A, Campins-Martí M. Enferm Infecc Microbiol Clin. 2013 May 29. doi:pii: S0213-005X(13)00124-9. 10.1016/j.eimc.2013.04.007. [Epub ahead of print] Spanish. PMID: 23725786 [PubMed - as supplied by publisher] Related citations Select item 23725785 125. -
Vaccines, Emerging Viruses, and How to Avoid Disaster Rino Rappuoli
Rappuoli BMC Biology 2014, 12:100 http://www.biomedcentral.com/1741-7007/12/100 INTERVIEW Open Access Vaccines, emerging viruses, and how to avoid disaster Rino Rappuoli Abstract Rino Rappuoli is a graduate of Siena University, where he also earned his PhD before moving to the Sclavo Research Center, the Italian vaccine institute, also in Siena. He then spent two years in the USA, mostly at Harvard with John Murphy and Alwin Pappenheimer working on a new diphtheria vaccine based on a non-toxic mutant of diphtheria toxin which has since become the basis for conjugate vaccines against haemophilus, meningococcus, and pneumococcal infections, before returning to the Sclavo Research Center where he developed an acellular vaccine based on a mutant pertussis toxin. With many achievements Rino Rappuoli in vaccine development to his credit, he is now Global Head of Vaccines Research and Development for Novartis Vaccines in Siena, and has most recently breaking out. Ebola virus is by far the most lethal that we pioneered reverse vaccinology, in which the genome have now, but all of the others are very dangerous. of the pathogen is screened for candidate antigenic and immunogenic vaccine components. We spoke to him about the potential for outbreaks of the kind we I know that there are ’flu vaccines, but are there are now seeing with Ebolavirus in West Africa, and licensed vaccines for any of the others? what can be done to prevent them. The answer is no - there are no vaccines for SARS, which emerged in 2003, there is no licensed vaccine for MERS, there is no licensed vaccine for Chikungunya, Ebolavirus disease has been much in the news there is no licensed vaccine for Ebola - so for most of recently because of the horrendous outbreak in these diseases there are no vaccines, because they are – West Africa but how many other rare, sporadic too rare to justify the economic investment. -
THE EVOLVING VIRUS Everything You What It Means How Long Before Need to Know About for the Roll-Out This Is Just the New Variants of Vaccines Another Cold?
THE HUMMING UNIVERSE Do gravitational waves permeate all of space-time? BEYOND LITHIUM Batteries you can make from common salt GENETIC EXCLUSION The diversity issue undermining medicine WEEKLY 23 January 2021 No3318 Australia $9.50 (Inc. GST) New Zealand NZ$9.50 (Inc. GST) Print Post Approved 100007877 COVID-19 THE EVOLVING VIRUS Everything you What it means How long before need to know about for the roll-out this is just the new variants of vaccines another cold? PARENTAL BURNOUT Why it’s time to take it seriously PLUS SAVING THE NORTHERN WHITE RHINO / UNSWATTABLE FLIES / BIN BAG SMELL / HOW TO SPOT A LIAR / OLDEST ANIMAL PAINTING News, ideas and innovation www.newscientist.com 210123_R_Cov_EvolvingVirus.indd 66 19/1/21 23:04 The leader Time to adapt As the coronavirus mutates, we will need to adjust our approach to it JUST one month ago, the world Now the virus has picked up need for tweaks to vaccines or new was already struggling to contain mutations that allow it to spread treatments (see page 10). the spread of the coronavirus. more easily and, in some cases, The news of these new variants has Now the challenge has become that could help it evade our coincided closely with the widespread even harder. The emergence of new immune system (see page 8). and very welcome roll-out of vaccines variants with different properties has A faster-spreading virus leads against covid-19. These vaccines offer changed the rules of engagement. to more infections, as has been seen us a way out of the pandemic, but we That the coronavirus should evolve already knew it would be a long road isn’t surprising – this is what viruses “ A virus that can evade our to vaccinating almost the entire adult do. -
Drugs and Vaccines Will Be Necessary to Control Tuberculosis
applied sciences Editorial Drugs and Vaccines Will Be Necessary to Control Tuberculosis Rino Rappuoli 1,2,3 1 GSK, 53100 Siena, Italy; [email protected] 2 Monoclonal Antibody Discovery Lab, Fondazione Toscana Life Sciences, 53100 Siena, Italy 3 Imperial College London, London SW7 2AZ, UK Received: 5 June 2020; Accepted: 9 June 2020; Published: 10 June 2020 For most infectious diseases, vaccines are used to prevent infection and drugs are used for acute therapy and eradication of established infections. This is not the case for tuberculosis, where BCG, the vaccine against tuberculosis, which is given to most children in low- and middle-income countries, does not prevent infection, but it is only effective in decreasing infant mortality. The consequence is that infection occurs in one third of the global population and, following infection, the bacterium establishes a lifelong chronic presence. More than 2 billion people today are chronically infected. The immune system of the chronically infected individuals is effective to keep the bacterium at bay for most of the time, however there are circumstances where the immune system becomes temporarily or permanently weaker and the bacterium escapes the immunity and causes severe disease. The consequence are 1.5 million deaths every year. In addition to the only partially effective BCG vaccine against tuberculosis, also the available therapies for tuberculosis are suboptimal. They require months to eradicate the infection and they are largely ineffective due to the increasing rate of bacteria resistant to antibiotics. The question we have is why in 2020 we still rely on a vaccine developed a century ago (in 1922) and why we do not have better drugs. -
Curriculum Vitae
CURRICULUM VITAE RINO RAPPUOLI Business address GSK Vaccines Via Fiorentina, 1 53100 Siena – ITALY Office: +39-0577-243414 Email: [email protected] Current positions 2015 - to date Chief Scientist and Head External R&D, GlaxoSmithKline Vaccines (Siena, Italy). Previous positions 2017 - 2019 Professor of Vaccines Research, Faculty of Medicine, Imperial College (London, United Kingdom) 2014 Global Head Research and Development, Novartis Vaccines (Siena, Italy). 2007-2015 Founder and chairman of the Board of the Novartis Vaccines Institute for Global Health (Siena, Italy). 2006 Global Head Vaccines Research, Novartis Vaccines & Diagnostics (Siena, Italy). 2003 Chief Scientific Officer and Vice President Vaccines Research, Chiron Corporation (Emeryville, USA). 1996 Vice President Vaccines Research, Chiron Corporation (Emeryville, USA). 1992 Head of Research of IRIS, the Chiron S.p.A. Research Institute (Siena, Italy). 1988-1991 Head of the Sclavo Research and Development (Siena, Italy). 1985-1987 Head of the laboratory of Bacterial Vaccines at the Sclavo Research Center. Worked on the molecular genetics of Bordetella pertussis and the development of a new vaccine against whooping cough. 1982-1984 Sclavo Research Center, Worked on the molecular biology of Corynebacterium diphtheriae and the development of a new vaccine against diphtheria. 1980-1981 Visiting scientist at the Harvard Medical School (Boston, USA). Worked on the molecular biology of bacteriophages of Corynebacterium diphtheriae in the laboratory of John Murphy. 1979 Visiting scientist for four months at the Rockefeller University (New York, USA). Worked on the purification of gonococcal antigens in the laboratory of Emil Gotschlich. 1978-1984 Staff scientist at the Sclavo Research Center (Siena, Italy). -
Profile of Rino Rappuoli
PROFILE Profile of Rino Rappuoli ino Rappuoli grew up in the shadow of what he describes as a testament to the devastating impact of infectious disease: Rthe unfinished wall of the Siena Cathe- dral in Siena, Italy. When the plague hit the city in 1348, it slashed the popula- tion from 100,000 to 30,000. ‘‘It basically shut down one of the most powerful economies of the time, and that momen- tum was lost forever. I see it as an ex- ample of what could happen today with pandemic influenza,’’ says Rappuoli, whose current research focuses on devel- oping a vaccine for avian influenza. Rappuoli, currently the Global Head of Vaccines Research for Novartis Vaccines & Diagnostics (Siena, Italy), was elected as a foreign associate of the National Academy of Sciences in 2005. He has spent his career developing vaccines for pertussis, meningitis, and Helicobacter pylori and is jointly responsible for engi- neering the carrier protein used in many conjugate vaccines. He is credited with launching the field of reverse vaccinology, the first fruits of which are revealed in his Inaugural Article in this issue of PNAS Rino Rappuoli (1), where he describes a universal vaccine for serogroup B meningococcus. fellowship at Siena’s Sclavo Research to Alwin Pappenheimer, who became a Bucolic Beginnings Center, the Italian vaccine institute that mentor to Rappuoli. ‘‘He was one of Rappuoli was born in 1952, in Radicofani, had been developing and producing vac- the fathers of microbiology and immun- Italy, a village 40 miles south of Siena. cines for almost a century. ology....Heisanother person who really When he was 11, his family moved closer shaped my career,’’ says Rappuoli. -
Deploy Vaccines to Fight Superbugs
PROGRAM ON THE GLOBAL DEMOGRAPHY OF AGING AT HARVARD UNIVERSITY Working Paper Series Deploy Vaccines to Fight Superbugs Rino Rappuoli, David E. Bloom, and Steve Black December 2017 PGDA Working Paper No. 142 http://www.hsph.harvard.edu/pgda/working/ Research reported in this publication was supported by the National Institute on Aging of the National Institutes of Health under Award Number P30AG024409. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. COMMENT WEATHER Research must HEALTH How people with MEDICINE Sanctions leave long OBITUARY Ronald Breslow, adapt to the demands Lyme disease were shadow for users of blood- pioneering organic chemist, of society p.168 finally vindicated p.174 clotting factor in Iran p.175 remembered p.176 EDUARDO SOTERAS/AFP/GETTY EDUARDO Vaccines can have an effect on antimicrobial resistance by reducing the number of ill people and avoiding unnecessary antibiotic prescriptions. Deploy vaccines to fight superbugs Immunizations combined with antibiotics could be our best shot at combating drug-resistant microbes, argue Rino Rappuoli, David E. Bloom and Steve Black. acteria, viruses, parasites and fungi Antimicrobials alone won’t be able to stakeholders need to see antibiotics and that are resistant to drugs cause mitigate the threat. The supply of naturally vaccines as complementary tools. Here we 700,000 deaths each year. By 2050, such occurring antibiotics seems thin. And efforts focus on antibiotic-resistant bacteria, for B‘superbugs’, inured to treatments, could cause to engineer new ones have floundered. which the need for solutions is most urgent. -
Sitting Down with Johannes Khinast
APRIL 2021 # 74 Upfront In My View NextGen Sitting Down With The risk profile of Analyzing capsids for Unit-level traceability of Johannes Khinast – the only pharma-grade whey gene therapy glass containers science is good science 07 12 38 – 42 50 – 51 www.themedicinemaker.com Value beyond the vial When you have questions, we have answers. When evaluating your product against a reference standard, questions arise. Give yourself a cushion of confidence. When you need expert advice or are seeking a training course to help you with our reference standards, you’ll always have access to answers when you need them — with USP. Move forward with more confidence: Contact USP. 1-301-881-0666 | usp.org/chemical-medicines A Roadmap for Access We must secure sustainable markets to ensure patient Editorial access to generic and biosimilar medicines he pandemic has presented a unique challenge to healthcare systems and infrastructure, including the generic drug supply chain. Generic drug Tmanufacturers have met this challenge, ensuring a stable supply of life-saving medicines for patients throughout the pandemic. However, the long-term sustainability of the generic and emerging biosimilars medicines market faces threats. Policymakers should consider and address the unique challenges facing generics and biosimilars to maintain long-term access to cost savings for patients. In its latest paper, Securing Sustainable Markets, the Association for Accessible Medicines (AAM) announced a series of policy proposals intended to ensure patient access to lower-cost medicines (1). Generic drugs face competitive imbalances in the market, such as a highly consolidated drug purchasing system controlled by a few major organizations, combined with ill-advised government policies. -
The GAVI Alliance
GLOBAL PROGRAM REVIEW The GAVI Alliance Global Program Review The World Bank’s Partnership with the GAVI Alliance Main Report and Annexes Contents ABBREVIATIONS .................................................................................................................................. V ACKNOWLEDGMENTS ........................................................................................................................ XI PROGRAM AT A GLANCE: THE GAVI ALLIANCE ............................................................................ XII KEY BANK STAFF RESPONSIBLE DURING PERIOD UNDER REVIEW ........................................ XIV GLOSSARY ......................................................................................................................................... XV OVERVIEW ........................................................................................................................................ XVII GAVI ALLIANCE MANAGEMENT RESPONSE .............................................................................. XXV WORLD BANK GROUP MANAGEMENT RESPONSE ................................................................... XXIX CHAIRPERSON’S SUMMARY ......................................................................................................... XXXI 1. THE WORLD BANK-GAVI PARTNERSHIP AND THE PURPOSE OF THE REVIEW ...................... 1 Evolution of GAVI ..................................................................................................................................................... -
Vaccinology in the Genome Era
Vaccinology in the genome era C. Daniela Rinaudo, … , Rino Rappuoli, Kate L. Seib J Clin Invest. 2009;119(9):2515-2525. https://doi.org/10.1172/JCI38330. Review Series Vaccination has played a significant role in controlling and eliminating life-threatening infectious diseases throughout the world, and yet currently licensed vaccines represent only the tip of the iceberg in terms of controlling human pathogens. However, as we discuss in this Review, the arrival of the genome era has revolutionized vaccine development and catalyzed a shift from conventional culture-based approaches to genome-based vaccinology. The availability of complete bacterial genomes has led to the development and application of high-throughput analyses that enable rapid targeted identification of novel vaccine antigens. Furthermore, structural vaccinology is emerging as a powerful tool for the rational design or modification of vaccine antigens to improve their immunogenicity and safety. Find the latest version: https://jci.me/38330/pdf Review series Vaccinology in the genome era C. Daniela Rinaudo, John L. Telford, Rino Rappuoli, and Kate L. Seib Novartis Vaccines, Siena, Italy. Vaccination has played a significant role in controlling and eliminating life-threatening infectious diseases through- out the world, and yet currently licensed vaccines represent only the tip of the iceberg in terms of controlling human pathogens. However, as we discuss in this Review, the arrival of the genome era has revolutionized vaccine develop- ment and catalyzed a shift from conventional culture-based approaches to genome-based vaccinology. The availabili- ty of complete bacterial genomes has led to the development and application of high-throughput analyses that enable rapid targeted identification of novel vaccine antigens.