GE Healthcare DCVMN Introduction to PD for Vaccine

Total Page:16

File Type:pdf, Size:1020Kb

GE Healthcare DCVMN Introduction to PD for Vaccine Introduction to process development for vaccine production DCVMN 10 March 2017 Need for updated vaccine processing and process optimization for global access Process development and optimization training workshop—DCVMN Taipei Speakers Dr. Mats Lundgren Mia Bennemo Customer Applications Director, Life Sciences Senior Research Engineer, Life Sciences GE Healthcare, Sweden GE Healthcare, Sweden 29256323AA I Mar. 2017 3 Preliminary agenda • Introduction to process development • Upstream process development for vaccine production • Downstream process development • Process economy • Quality by design (QbD) in process • Group discussion exercise—how to development overcome technical and economical • Practical exercise: QbD challenges in DCVMN companies • Future scenarios, wrap up discussion • Analytics and test • Lunch break 29256323AA I Mar. 2017 4 Introduction to process development for vaccine production 29256323AA I Mar. 2017 5 Outline • Vaccine process history • Why is process development for vaccines important? • Vaccine processing • Single-use technologies for vaccine manufacturing • Conclusions 29256323AA I Mar. 2017 6 Historic vaccine timeline 1955 : Injectable polio vaccine introduced 2006 : First cancer 1796 : Edward Jenner vaccine 1986 : First develops smallpox 1967 : Smallpox HPV vaccine recombinant vaccine eradication program human vaccine started 1979 : Smallpox eradicated from the world 1885 : Pasteur develops rabies vaccine 1962 : Oral polio 2010 : First vaccine introduced 1994 : Last case of therapeutic 1943 : Egg-based polio in the cancer vaccine influenza vaccine Americas approved 29256323AA I Mar. 2017 7 The evolution of vaccine processes • First generation processes: • Focus on upstream, optional inactivation • Second generation processes: • Separation based on centrifugation, filtration • Currently developed processes: • Quality based approach: QbD • Focus on entire process including purification and virus safety 29256323AA I Mar. 2017 8 Historic vaccine timeline: propagation 1955 : Injectable polio vaccine introduced 2006 : First cancer 1796 : Edward Jenner vaccine 1986 : First develops smallpox 1967 : Smallpox HPV vaccine recombinant vaccine eradication program human vaccine started In vivo In ovo Primary cell line Diploid cell line Continuous cell line 1979 : Smallpox eradicated 1885 : Pasteur from the world develops rabies vaccine 1962 : Oral polio 2010 : First vaccine introduced 1994 : Last case of therapeutic 1943 : Egg-based polio in the cancer vaccine influenza vaccine Americas approved 29256323AA I Mar. 2017 9 Historic vaccine timeline: purification 1955 : Injectable polio vaccine introduced 2006 : First cancer 1796 : Edward Jenner vaccine develops smallpox 1967 : Smallpox 1986 : First HPV vaccine vaccine eradication program recombinant started human vaccine Non-purified Filtration Filtration/centrifugation Chromatography Quality by design 1979 : Smallpox eradicated 1885 : Pasteur from the world develops rabies vaccine 1962 : Oral polio 2010 : First vaccine introduced 1994 : Last case of therapeutic 1943 : Egg-based polio in the cancer vaccine influenza vaccine Americas approved 29256323AA I Mar. 2017 10 The history of polio vaccines and GE 1955 1960 1960s 1970s 1980s 2010s Inactivated polio Attenuated polio Collaboration New IPV Switch to Vero Updating the IPV vaccine (IPV) vaccine launched between Prof. Van purification cell production processes using launched (Salk (Sabin type) Wezel (RIVM/NVI method using using Cytodex™ 1 modern Type) Netherlands) and GE's microcarriers technology from GE (former chromatography GE Pharmacia) around resins microcarrier cultures of primary monkey cells 29256323AA I Mar. 2017 11 Polio vaccine process 1. 2. 3. 5. 6. 7. 4. Cell Cell Production & Chromato- Chromato- Virus inactivation & Concentration expansion 1 expansion 2 filtration graphy 1 graphy 2 sterile filtration UPSTREAM DOWNSTREAM 1 Cytodex™ 1 (3g/L, 15 L) 3 0.45/0.22 µm serum containing media, trypsination removal of cell debris on depth filters cell transfer 4 Tangential flow filtration (TFF), 100 kD flat sheet 2 Virus concentration Cytodex 1 (3 g/L, 40 L) recirculation grow cells to 5 × 10 6 cells/mL 5 trypsination, cell transfer Sepharose™ CL 6B resin cell debris and host cell protein (HCP) removal 3 Lower reactor temperature at infection 6 wash cells to change to serum-free media DEAE Sephadex™ A50 resin purification, DNA, and HCP removal 7 0.025 % formaldehyd,13 days, 37 °C 7 0.2 µm Production system Vaccine type Reference Vero cell line Polio vaccine (IPV). Naked virus (~ 30 nm). Type 1, 2, and 3 subtypes in the Netherlands Vaccine Institute (NVI) vaccine. (Sabine –OPV, Sabine-IPV, Salk-IPV) - Vaccine 29, p.7188– 7196, 2011 - www.plosone.org, 1 December 2013, Vol. 8, Issue 12 29256323AA I Mar. 2017 12 Why is process development for vaccines important? 29256323AA I Mar. 2017 13 What are the challenges for vaccine producers? Design of aged processes Adaptation to changing markets Access to new vaccine technology • Many “weak steps”, low yield, • Markets for classic vaccines • Virus-like particles (VLP) • low robustness shrink in developed markets with High safety • Low immunogenicity high prices • Lack of platforms, re-use of • Complex processes technology modules • Need to remove hurdles for • rec Antigens and adjuvants • Open handling and regulatory investment and improvement, • Easy processing concerns including regulatory hurdles • Good safety • Immunogenicity dependent • Regulatory practice does not • Reduce cost for highest standard on adjuvant support new technology production technology implementation • …and more • Viral vectors • CAPEX demand very high due • Overcome lack of flexibility in • Plasmids, mRNA to weak processes production infrastructure • Cells • Economy very dependent on • Technologies in its infancy scale CAPEX = capital expenditure 29256323AA I Mar. 2017 14 What are the challenges for vaccine producers? Design of aged processes Adaptation to changing markets Access to new vaccine technology • Many “weak steps”, low yield, • Markets for classic vaccines • Virus-like particles • low robustness shrink in developed markets with High safety • Low immunogenicity high prices • Lack of platforms, re-use of • Complex processes technology modules • Need to remove hurdles for • rec AntigensImplement and adjuvants Improved • Open handling and regulatory investmentFlexible, and right- improvement, • Easy processingplatform scalability,concerns • Good safetytechnologies combine includingscaled regulatory hurdles combine yield and • Immunogenicityupstream dependent • Regulatory practice does not production process • Reduce cost for highest standard on adjuvant and support new technology infrastructure robustness implementation productionand facilities technology • downstream with modern …and more • Viral vectors • CAPEX demand very high due • Overcome lack of flexibility in technology • Plasmids, mRNA to weak processes production infrastructure • Cells • Economy very dependent on • Technologies in its infancy scale 29256323AA I Mar. 2017 15 Process development—trends and solutions • Quality must never be compromised • You always need to spend enough time and money to understand what the process does to the product • Your process will be most efficient in terms of time and cost, if you build its performance on solid understanding 29256323AA I Mar. 2017 16 Vaccines are difficult to characterize Monoclonal antibodies Vaccines Implications Often well-characterized Often difficult to characterize Less definitive analytical comparability pathways Less ability to monitor product Quality in mid-process Clear link to mechanism of Difficult to establish clinical Challenging to improve process action (MoA) and/or biomarker potency surrogates post-licensure surrogate for clinical performance Consistent process and product Sometimes more complex, less Variability over product/process predictable process/product life cycle Therapeutic patient population Prophylactic patient population “Process is product” philosophy to assure Quality Well-understood process; good Less understood process; Empirical process models for detectability for test methods difficult to measure attribute linking parameter inputs to changes Quality outputs More stringent threshold for reporting manufacturing changes 29256323AA I Mar. 2017 2017 -03- 13 A-VAX case study objectives I Substantial changes in quality systems and regulatory approaches might be needed • Apply QbD to develop a robust vaccine manufacturing process. This includes: • Risk-based approaches to vaccine development • Leveraging of science to gain process and product understanding • Continuous improvement • Merging of process and analytical controls for vaccine manufacturing • Make the rationale for development more transparent in regulatory submissions 29256323AA I Mar. 2017 18 A-VAX case study objectives II Substantial changes in quality systems and regulatory approaches might be needed • Document techniQues for safe and effective vaccines to reach market more Quickly • Strive to make reviews more efficient; decrease the number of post- approval supplements needed • Develop realistic examples to better illustrate how QbD can be applied within the development space and overall product Quality system • Highlight and/or develop tools, frameworks, etc., to enable ICH Q8, Q9, Q10, and Q11 implementation strategies • Tie key benefits with the strategies illustrated in the case study 29256323AA I Mar. 2017 19 Note of caution on A-VAX It should be understood that that
Recommended publications
  • 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).
    [Show full text]
  • 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
    [Show full text]
  • 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.
    [Show full text]
  • 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.
    [Show full text]
  • The Immunological Basis for Immunization Series
    The Immunological Basis for Immunization Series Module 23: Influenza Vaccines Immunization, Vaccines and Biologicals The immunological basis for immunization series: module 23: influenza vaccines (Immunological basis for immunization series; module 23) ISBN 978-92-4-151305-0 © World Health Organization 2017 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 23: influenza vaccines. Geneva: World Health Organization; 2017 (Immunological basis for immunization series; module 23). Licence: CC BY-NC-SA 3.0 IGO.
    [Show full text]
  • 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.
    [Show full text]
  • Evaluation of in Ovo Vaccination of DNA Vaccines for Campylobacter Control in Broiler Chickens ⇑ Xiang Liu, Lindsay Jones Adams, Ximin Zeng, Jun Lin
    Vaccine 37 (2019) 3785–3792 Contents lists available at ScienceDirect Vaccine journal homepage: www.elsevier.com/locate/vaccine Evaluation of in ovo vaccination of DNA vaccines for Campylobacter control in broiler chickens ⇑ Xiang Liu, Lindsay Jones Adams, Ximin Zeng, Jun Lin Department of Animal Science, The University of Tennessee, 2506 River Drive, Knoxville, TN 37996, USA article info abstract Article history: Campylobacter is the leading bacterial cause of human enteritis in developed countries. Chicken is a major Received 7 August 2018 natural host of Campylobacter. Thus, on-farm control of Campylobacter load in poultry would reduce the Received in revised form 13 May 2019 risk of human exposure to this pathogen. Vaccination is an attractive intervention measure to mitigate Accepted 20 May 2019 Campylobacter in poultry. Our previous studies have demonstrated that Campylobacter outer membrane Available online 3 June 2019 proteins CmeC (a component of multidrug efflux pump) and CfrA (ferric enterobactin receptor) are fea- sible and promising candidates for vaccine development. In this study, by targeting these two attractive Keywords: vaccine candidates, we explored and evaluated a new vaccination strategy, which combines the in ovo Campylobacter jejuni vaccination route and novel DNA vaccine formulation, for Campylobacter control in broilers. We observed DNA vaccine In ovo vaccination that direct cloning of cfrA or cmeC gene into the eukaryotic expression vector pCAGGS did not lead to suf- Poultry ficient level of production of the target proteins in the eukaryotic HEK-293 cell line. However, introduc- Kozak sequence tion of the Kozak consensus sequence (ACCATGG) in the cloned bacterial genes greatly enhanced production of inserted gene in eukaryotic cells, creating desired DNA vaccines.
    [Show full text]
  • Instituto Finlay
    Resumen de la información publicada por la OMS sobre los candidatos vacunales contra la COVID-19 en desarrollo a nivel mundial Última actualización por la OMS: 9 de abril de 2021. Fuente de información utilizada: 87 candidatos vacunales en evaluación clínica y 186 en evaluación preclínica. Candidatos vacunales en evaluación clínica por plataforma Candidatos vacunales más avanzados a nivel global Desarrollador de la vacuna/fabricante/país Plataforma de la vacuna Fase Sinovac/China Virus Inactivado 4 Wuhan Institute of Biological Products/Sinopharm/China Virus Inactivado 3 Beijing Institute of Biological Products/Sinopharm/China Virus Inactivado 3 University of Oxford/AstraZeneca/Reino Unido Vector viral no replicativo 4 CanSino Biological Inc./Beijing Institute Biotechnology/China Vector viral no replicativo 3 Gamaleya Research Institute/Rusia Vector viral no replicativo 3 Janssen Pharmaceutical Companies/Estados Unidos Vector viral no replicativo 3 Novavax/Estados Unidos Subunidad proteica 3 Moderna/NIAID/Estados Unidos ARN 4 BioNTech/Fosun Pharma/Pfizer/Estados Unidos ARN 4 Anhui Zhifei Longcom Biopharmac./Inst. Microbiology, Chinese Academy Sciences Subunidad proteica 3 CureVac AG/Alemania ARN 3 Institute of Medical Biology/Chinese Academy of Medical Sciences Virus inactivado 3 Research Institute for Biological Safety Problems, Kazakhstan Virus inactivado 3 Zydus Cadila Healthcare Ltd./India ADN 3 Bharat Biotech/India Virus Inactivado 3 Sanofi Pasteur + GSK/Francia/Gran Bretaña Subunidad proteica 3 Instituto Finlay de Vacunas/Cuba
    [Show full text]
  • Frequently Asked Questions on Viral Tumor Diseases Compiled by the AAAP Tumor Virus Committee (2012)
    Frequently Asked Questions on Viral Tumor Diseases Compiled by the AAAP Tumor Virus Committee (2012) 1. Can you expect 100% protection against MDV field challenge in vaccinated birds? No. As with all other vaccines, achieving 100% protection under field conditions is not possible from a biological viewpoint. In chicken flocks with healthy immune system and that are properly vaccinated and raised under adequate management, the losses are low without a significant impact on livability and/or performance. In cases of severe field challenge at an early age in vaccinated layers and breeders, mortality around 2-5% and broiler condemnations due to MD at ~0.05 % have been observed. 2. Which vaccine or vaccine combination may offer the best protection against field challenge in broilers, broiler breeders, or commercial layers? Broilers are vaccinated with HVT or HVT+SB1. HVT+SB1 is used in locations where very virulent (vv)MDVs are prevalent and the HVT vaccine alone does not provide an optimal protection. In some cases, particularly in heavy birds (e.g. roosters), HVT+SB1 may not provide adequate protection due to the prevalence of vv+MDV. In these circumstances, the bivalent HVT+CVI988(Rispens) or the trivalent HVT+SB1+CVI988(Rispens) vaccine has been used. Using below recommended dose of plaque forming units (PFU) is a common practice in broiler vaccination, however, it should be noted that this practice can lead to MD breaks in the face of severe field challenge and may play a role in accelerating MD virus evolution towards greater virulence. Breeders and Layers are commonly vaccinated with the HVT+CVI988(Rispens) vaccine using the full dose providing these long-lived birds with the broadest protection against MD.
    [Show full text]
  • Intranasal Powder Live Attenuated Influenza Vaccine Is
    www.nature.com/npjvaccines ARTICLE OPEN Intranasal powder live attenuated influenza vaccine is thermostable, immunogenic, and protective against homologous challenge in ferrets Jasmina M. Luczo 1,2, Tatiana Bousse3, Scott K. Johnson1, Cheryl A. Jones1, Nicholas Pearce3, Carlie A. Neiswanger1, Min-Xuan Wang4, ✉ Erin A. Miller4, Nikolai Petrovsky 5,6, David E. Wentworth 3, Victor Bronshtein4, Mark Papania7 and Stephen M. Tompkins 1,2,8 Influenza viruses cause annual seasonal epidemics and sporadic pandemics; vaccination is the most effective countermeasure. Intranasal live attenuated influenza vaccines (LAIVs) are needle-free, mimic the natural route of infection, and elicit robust immunity. However, some LAIVs require reconstitution and cold-chain requirements restrict storage and distribution of all influenza vaccines. We generated a dry-powder, thermostable LAIV (T-LAIV) using Preservation by Vaporization technology and assessed the stability, immunogenicity, and efficacy of T-LAIV alone or combined with delta inulin adjuvant (Advax™) in ferrets. Stability assays demonstrated minimal loss of T-LAIV titer when stored at 25 °C for 1 year. Vaccination of ferrets with T-LAIV alone or with delta inulin adjuvant elicited mucosal antibody and robust serum HI responses in ferrets, and was protective against homologous challenge. These results suggest that the Preservation by Vaporization-generated dry-powder vaccines could be distributed without refrigeration and administered without reconstitution or injection. Given these significant advantages for vaccine distribution and delivery, further research is warranted. 1234567890():,; npj Vaccines (2021) 6:59 ; https://doi.org/10.1038/s41541-021-00320-9 INTRODUCTION cellular immune responses12. Although some LAIVs require Influenza viruses pose a dual threat to global human health— healthcare workers (HCWs) to mix the dry vaccine with a diluent, annual seasonal epidemics and sporadic global pandemics.
    [Show full text]
  • Study on In-Ovo Vaccination by Needle-Free Injection
    Proceedings of the 6th World Congress on New Technologies (NewTech'20) Prague, Czech Republic Virtual Conference – August, 2020 Paper No. ICBB 115 DOI: 10.11159/icbb20.115 Study on In-Ovo Vaccination by Needle-Free Injection Ko-Jung Huang1, Wei-Chih Chen1, Ching-Wei Cheng2 1 Department of Bio-industrial Mechatronics Engineering, National Chung Hsing University No.145 Xingda Rd., South Dist., Taichung City 402, Taiwan (R.O.C.) First. [email protected] 2 College of Intelligence, National Taichung University of Science and Technology No.129, Sec.3, Sanmin Rd, North Dist., Taichung City 404, Taiwan (R.O.C.) Third. [email protected] Extended Abstract Chick immunization in Taiwan in the current stage is done in the traditional artificial way via chick subcutaneous injection, eye drops, spray vaccine, or getting the vaccine mixed with feed and other methods for epidemic prevention. In addition to the traditional artificial way, in 1982, Sharma and Burmester proved the success of egg injection via Marek's vaccine immunization under normal laboratory conditions for the first time [1]. Eighty-five percent of the US chicken industry deployed egg injection as an important method of chicken embryo immunization. Presently, many countries have developed the automated egg syringe system. Due to congenital biological differences of individual eggs, the vaccine cannot be accurately injected; there is lack of control of the needle-hit position. This may affect the growth of the chicken embryo. Wakenell et al. Published the Marek's vaccine in 2002 and the efficacy of the vaccine. Sparring time at embryonic age of 18 days, vaccines in the amniotic cavity can be absorbed with other nutrients together with chicken embryo.
    [Show full text]
  • Puzzling Inefficiency of H5N1 Influenza Vaccines In
    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).
    [Show full text]