DOCSLIB.ORG

Copyright by Irnela Bajrovic 2020 the Dissertation Committee for Irnela Bajrovic Certifies That This Is the Approved Version of the Following Dissertation

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Copyright by Irnela Bajrovic 2020 the Dissertation Committee for Irnela Bajrovic Certifies That This Is the Approved Version of the Following Dissertation Copyright by Irnela Bajrovic 2020 The Dissertation Committee for Irnela Bajrovic Certifies that this is the approved version of the following Dissertation: Development and Characterization of Thermostable Thin Films as a Novel Vaccine Dosage Form Committee: Maria A. Croyle, Supervisor Hugh D. Smyth Debadyuti Ghosh Jennifer A. Maynard Charles R. Middaugh For my parents Džemal and Rahima, and my sister, Minela without whom none of this would have been possible. Acknowledgements I joined Dr. Maria Cryole’s lab in 2014 as an undergraduate student hoping to gain some research experience and learn about vaccine delivery. Little did I know that one semester would turn into six years and two degrees that have forever changed my life for the better. First and foremost, I would like to thank Dr. Croyle for giving me the guidance and support to learn and grow as a scientist. I will treasure the time we spent together and everything I learned from her. I would also like to thank my committee members Dr. Hugh Smyth, Dr. Debadyuti Ghosh, Dr. Jennifer Maynard, and Dr. Charles Middaugh for their guidance, support, and encouragement. Special thanks to Stephen Schafer who served as great sounding board and brainstorm partner. To past and present Croyle lab members Dr. Kristina Jonsson-Schmunk, Trang Doan, and Matthew Le, I also say thank you. Your advice and support contributed to the completion of the projects in this document and I am grateful for the friendships we have built. I would also like to thank my family for always encouraging me and reminding me that I am capable of anything I set my mind to. My wonderful parents, Rahima and Džemal, have sacrificed so much to give my sister and I a better life. I hope to honor their sacrifice with this document and a steadfast devotion to science. To my sister Minela, who taught me confidence and ambition, I am eternally indebted. She is my forever role model and I hope to make her proud. And to the friends that are like family, Lauren Cardenas, Zainab Shahid, Shehnaz Haqqani, Saad Dawoodi, Melissa Soto, and Ahlam Qerqez a special thanks for reminding me of the strength I have within. And finally, I would like to thank Karen Stewart, for opening up her home to me while I was preparing this document and providing me with a comfortable and quiet space to focus on my work. I will never forget her generosity. iv Abstract Development and Characterization of Thermostable Thin Films as a Novel Vaccine Dosage Form Irnela Bajrovic, PhD The University of Texas at Austin, 2020 Supervisor: Maria A. Croyle Thermostabilization of vaccines can significantly simplify vaccine storage and distribution processes, eliminating the need for cold-chain maintenance, and resulting in global access to life-saving vaccines. Despite this benefit, all approved vaccines for use by the Food and Drug Administration must be refrigerated for long term storage in order to guarantee potency. The first study described in this thesis demonstrated that formulation of live adenovirus in the novel thin film matrix protects the virus from degradation at 4°C and 20°C for a minimum of three months, as well as 14 days at 37°C and 5 days at 40°C. The film matrix protected virus through 16 freeze-thaw cycles as well. As formulations prepared with surfactant outperformed those without it, the second study was designed to characterize and evaluate the intermolecular interactions between the surfactant and adenovirus capsids. in order to better understand the surfactants contribution to stability. The data suggested that surfactant stabilizes adenovirus by preventing aggregation of capsids via electrostatic and hydrophobic interactions. Additionally, the other formulation components in our multi-component preparation mitigates the interactions between adenovirus and the surfactant without interfering with stability. Lastly, the principles of surfactant stabilization were applied to the identification of alternative excipients for stabilization v of a virus with different properties from adenovirus, H1N1 influenza. The third study evaluated the ability of the thin film platform to induce an immune response and the impact of a natural adjuvants on the cytokine response and bioavailability of the vaccine dose. A preliminary screen demonstrated that vaccination with the thin film platform resulted in a stronger humoral response following mucosal vaccination than with traditional intramuscular vaccination. Additionally, the optimized formulation improved bioavailability of the viral dose across human buccal explants. Further characterization of the immune response also revealed that sublingual routes induced a strong TH1 polarized immune response which resulted in greater protective efficacy than intramuscular immunization. Taken together, these studies identified a novel thin film platform capable of stabilizing adenovirus at ambient temperatures, provide key insights into viral stabilization in the novel thin film platform, and illustrate the utility of the thin film as mucosal vaccine dosage form. vi Development and Characterization of Thermostable Thin Films as a Novel Vaccine Dosage Form by Irnela Bajrovic Dissertation Presented to the Faculty of the Graduate School of The University of Texas at Austin In Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy The University of Texas at Austin December 2020 vii Table of Contents Chapter 1: Breaking the Cold Chain for Viral Vaccines: A Move Toward Needle Free Delivery .......................................................................................................................................... 1 1.1 Physical Properties of Viruses ............................................................................................... 5 1.2 Chemical and Environmental Stressors which Impact Virus Stability ............................... 10 1.3 Principles of Formulation Design ....................................................................................... 13 1.4 Liquid Formulations for Viral Stabilization ........................................................................ 15 1.5 Solid Formulations for Vaccine Stabilization ..................................................................... 20 1.6 Spray-Drying ....................................................................................................................... 24 1.7 Film Formation for Vaccine Stabilization ........................................................................... 26 1.8 General Overview: Immune Response to Virus Based Vaccines ....................................... 31 1.9 Administration of Vaccines: The Injectables ...................................................................... 34 1.10 Intranasal Vaccine Delivery .............................................................................................. 38 1.11 Oral Vaccine Delivery ....................................................................................................... 41 1.11.1 Administration of Vaccines: Sublingual and Buccal Delivery ................................... 43 1.12 Objectives .......................................................................................................................... 51 1.13 References ......................................................................................................................... 55 Chapter 2: Novel Technology for Storage and Distribution of Live Vaccines and Other Biological Medicines at Ambient Temperature ....................................................................... 74 2.1 Introduction ......................................................................................................................... 74 2.2 Materials and Methods ........................................................................................................ 79 2.2.1 Materials ....................................................................................................................... 79 2.2.2 Adenovirus Production and Purification ...................................................................... 80 2.2.3 Formulation Screening ................................................................................................. 80 2.2.4 Rate of Release Analysis .............................................................................................. 81 2.2.5 Young’s Modulus and Percent Elongation ................................................................... 81 2.2.6 Viscosity Measurements ............................................................................................... 82 2.2.7 Short-Term Stability ..................................................................................................... 82 2.2.8 Freeze-Thaw Studies .................................................................................................... 83 2.2.9 Scanning Electron Microscopy ..................................................................................... 83 2.2.10 Differential Scanning Calorimetry ............................................................................. 83 2.2.11 X-ray Powder Diffraction ........................................................................................... 83 2.2.12 Fourier Transform Infrared Spectroscopy .................................................................. 84 2.2.13 Statistical Analysis ..................................................................................................... 84 viii 2.3 Results ................................................................................................................................
Load more

Recommended publications
  • Considerations for Causality Assessment of Neurological And
    Occasional essay J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp-2021-326924 on 6 August 2021. Downloaded from Considerations for causality assessment of neurological and neuropsychiatric complications of SARS- CoV-2 vaccines: from cerebral venous sinus thrombosis to functional neurological disorder Matt Butler ,1 Arina Tamborska,2,3 Greta K Wood,2,3 Mark Ellul,4 Rhys H Thomas,5,6 Ian Galea ,7 Sarah Pett,8 Bhagteshwar Singh,3 Tom Solomon,4 Thomas Arthur Pollak,9 Benedict D Michael,2,3 Timothy R Nicholson10 For numbered affiliations see INTRODUCTION More severe potential adverse effects in the open- end of article. The scientific community rapidly responded to label phase of vaccine roll- outs are being collected the COVID-19 pandemic by developing novel through national surveillance systems. In the USA, Correspondence to SARS- CoV-2 vaccines (table 1). As of early June Dr Timothy R Nicholson, King’s roughly 372 adverse events have been reported per College London, London WC2R 2021, an estimated 2 billion doses have been million doses, which is a lower rate than expected 1 2LS, UK; timothy. nicholson@ administered worldwide. Neurological adverse based on the clinical trials.6 kcl. ac. uk events following immunisation (AEFI), such as In the UK, adverse events are reported via the cerebral venous sinus thrombosis and demyelin- MB and AT are joint first Coronavirus Yellow Card reporting website. As of ating episodes, have been reported. In some coun- authors. early June 2021, approximately 250 000 Yellow tries, these have led to the temporary halting of BDM and TRN are joint senior Cards have been submitted, equating to around authors.
    [Show full text]
  • European Contact Lens Society of Ophthalmologists ECLSO
    European Contact Lens Society of Ophthalmologists ECLSO Course de Base en Contactologie I – IV Basiskurs in Kontaktologie I - IV Dr. med. Albert Franceschetti, Genève Michael Bärtschi, M.Sc.Optom. et M.Med.Educ.,Bern Optics and Contact Lenses What should I know about optics and physiological optics when I fit contact lenses ? Visual acuity = 1.0 • US notation 20/20 (20 feet) • Metric notation 6/6 (6 meters) • Decimal 10/10 (Monoyer) • Logarythmic Distance spectacles-eye • The position of the contact lens is different in relation to the eye. This is obviously the first criterion to take into consideration. • According to the power of the spectacles, the difference ǻ between the power of spectacle lenses and the contact lenses will be more or less important. Formula • DL power of the glasses (supposed perfect DL correction) DCL = -------------- 1 – d D • DCL power of the contact L lens (lens + tear meniscus) • d distance between the lens and the contact lens • ǻ difference between the power DCL and DL ǻ • ǻ = DCL –DL is always positive • ǻ = DCL –DL increases if the distance eye- glasses increases • The value d can be superior to 12mm if one uses trial lenses or refractor. Variation of powers between the two systems (contact lenses and spectacle) Distance eye- DL -20 -15 -10 -8 -5 +4 +10 glasses -16.13 -12.71 -8.93 -7.30 -4.72 +4.20 +11.36 DCL d=12m 3.87 2.29 1.07 0.70 0.28 0.20 1.36 m ǻ -15.38 -12.24 -8.70 -7.14 -4.65 +4.26 +11.76 DCL D=15 ǻ 4.62 2.76 1.30 0.86 0.35 0.26 1.76 mm Magnification • The distance eye-spectacles versus eye contact lens being different, the magnification of the retinal image will be different.
    [Show full text]
  • An Overview of COVID Vaccine Clinical Trial Results & Some Challenges
    An overview of COVID vaccine clinical trial results & some challenges DCVMN Webinar December 8th, 2020 Access to COVID-19 tools ACCESSACCESS TO TOCOVID-19 COVID-19 TOOLS TOOLS (ACT) (ACT) ACCELERATOR ACCELERATOR (ACT) accelerator A GlobalA GlobalCollaboration Collaboration to Accelerate tothe AccelerateDevelopment, the Production Development, and Equitable Production Access to New and Equitable AccessCOVID-19 to New diagnostics, COVID-19 therapeutics diagnostics, and vaccines therapeutics and vaccines VACCINES DIAGNOSTICS THERAPEUTICS (COVAX) Development & Manufacturing Led by CEPI, with industry Procurement and delivery at scale Led by Gavi Policy and allocation Led by WHO Key players SOURCE: (ACT) ACCELERATOR Commitment and Call to Action 24th April 2020 ACT-A / COVAX governance COVAX COORDINATION MEETING CEPI Board Co-Chair: Jane Halton Co-Chair: Dr. Ngozi Gavi Board Workstream leads + DCVMN and IFPMA-selected Reps As needed – R&D&M Chair; COVAX IPG Chair Development & Manufacturing Procurement and delivery Policy and allocation (COVAX) at scale Led by (with industry) Led by Led by R&D&M Investment Committee COVAX Independent Product Group Technical Review Group Portfolio Group Vaccine Teams SWAT teams RAG 3 COVAX SWAT teams are being set up as a joint platform to accelerate COVID- 19 Vaccine development and manufacturing by addressing common challenges together Timely and targeted Multilateral Knowledge-based Resource-efficient Addresses specific cross- Establishes a dialogue Identifies and collates Coordinates between developer technical and global joint effort most relevant materials different organizations/ challenges as they are across different COVID-19 and insights across the initiatives to limit raised and/or identified vaccines organizations broader COVID-19 duplications and ensure on an ongoing basis (incl.
    [Show full text]
  • Gene-Based Vaccines (GBV)
    Advanced Drug Delivery Reviews 170 (2021) 113–141 Contents lists available at ScienceDirect Advanced Drug Delivery Reviews journal homepage: www.elsevier.com/locate/addr Advances in gene-based vaccine platforms to address the COVID-19 pandemic Deborah Pushparajah a,1, Salma Jimenez a,c,1,ShirleyWonga,HibahAlattasa, Nafiseh Nafissi b, Roderick A. Slavcev a,b,c,⁎ a School of Pharmacy, University of Waterloo, 10A Victoria St S, Kitchener N2G 1C5, Canada b Mediphage Bioceuticals, 661 University Avenue, Suite 1300, Toronto, ON, M5G 0B7, Canada c Theraphage, 151 Charles St W Suite # 199, Kitchener, ON, N2G 1H6, Canada article info abstract Article history: The novel betacoronavirus, SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), has spread across Received 1 October 2020 the globe at an unprecedented rate since its first emergence in Wuhan City, China in December 2019. Scientific Received in revised form 23 December 2020 communities around the world have been rigorously working to develop a potent vaccine to combat COVID-19 Accepted 1 January 2021 (coronavirus disease 2019), employing conventional and novel vaccine strategies. Gene-based vaccine platforms Available online 7 January 2021 based on viral vectors, DNA, and RNA, have shown promising results encompassing both humoral and cell-mediated immune responses in previous studies, supporting their implementation for COVID-19 vaccine de- Keywords: Coronavirus velopment. In fact, the U.S. Food and Drug Administration (FDA) recently authorized the emergency use of two COVID-19 RNA-based COVID-19 vaccines. We review current gene-based vaccine candidates proceeding through clinical SARS-CoV-2 trials, including their antigenic targets, delivery vehicles, and route of administration.
    [Show full text]
  • Hatchery Disinfection Policy and Procedures
    MAINE DEPARTMENT OF INLAND FISHERIES & WILDLIFE Chapter 11 Disinfection Policy & Procedures Editors: David C. Rayner, Fish Culture Supervisor, Governor Hill State Fish Hatchery, Augusta, Maine (19XX- Present) & G. Russell Danner MS, DVM, Fish Pathologist, Fish Health Laboratory, Augusta, Maine (1998 – Present) Date: September 24, 1999. “Or if a person touches anything ceremonially unclean-whether the carcasses of unclean wild animals or of unclean livestock or of unclean creatures that move along the ground-even though he is unaware of it, he has become unclean and is guilty” Lev. 5:2 Several factors should be included in an evaluation of a disinfectant. A prerequisite for a disinfectant is its effectiveness against the expected spectrum of pathogens (Table 11- 1, 11-2, and 11-3). A general guideline for effective killing of pathogens by a disinfectant is a 5-log killing of bacteria and a 4-log killing of viruses. In addition to the activity of the disinfectant, its compatibility with devices should be reviewed in detail; this should include a review of data on devices that have been immersed for longer than recommended times. Instruments can be forgotten after immersion, and this mistake should not necessarily result in irreparable damage to the device. Other issues are toxicity, odor, compatibility with other compounds, and residual activity. Various and numerous organisms can cause diseases in fish. Viruses, bacteria, fungi, protozoan and many invertebrate animals are included in this list. No single disinfectant destroys them all. It is up to the applicant to decide what is the pathogen of most concern, and how it is to be reduced or eliminated.
    [Show full text]
  • U.S. EPA, Pesticide Product Label, 776 DISINFECTANT VIRUCIDE
    , 1-ls-lf9 UNITED ST ATES ENVIRONMENTAL PROTECTION AGENCY Carroll Company 2900 West Kingsley Road Garland, TX 75041 Subject: 776 Disinfectant, Virucide and Cleaner EPA Registration No. 4313-22 Amendment Dated November 9, 1998 Attn: Linda Kirk Kirby Director, Regulatory Compliance The amendment referred to above, submitted in connection with registration under the Federal Insecticide, Fungicide and Rodenticide Act, as amended, is acceptable. A stamped copy of the label is enclosed for your records. Submit one (I) copy ofthe finished printed label before this product is released for shipment. If you have any questions concerning the comments in this letter, you should contact Zenobia Jones at (703) 308-6198. Sincerely, ) JJ~lvJHdL Velma Noble Product Manager 31 Regulatory Management Branch I Antimicrobial Division (751 OW) COHCURRI!HCI!S ::::} ·m·I~ .Q........ ................ - ....................................... -................................ _............................. DATE ) . \-1i.-9l1... ....... ................... ................. .................................................................................... OFFICIAL FILE COpy Primed Oft R~cye/~d Paper ~' '....,-. " DISINFECTANT, UIRUCIDE* AND CLEANER FOR HOSPITAL INSTITUTIONAL ACTIVE INGREDIENT: AND iNDUSTRIAL USE Alkyl (C14 50%, C12 40%, C16 10%) dimelhyl • benzyl ammonium chloride........... 3.3 Yo ·Hum8n immunodeficiency virus, Type 1 (HIV-l) INERT INGR~DIENTS .................. 96.7% KEEP OUT OF REACH OF CHILDREN DANGER See back panel for additional precautionary
    [Show full text]
  • Chemical Disinfectants | Disinfection & Sterilization Guidelines | Guidelines Library | Infection Control | CDC 3/19/20, 14:52
    Chemical Disinfectants | Disinfection & Sterilization Guidelines | Guidelines Library | Infection Control | CDC 3/19/20, 14:52 Infection Control Chemical Disinfectants Guideline for Disinfection and Sterilization in Healthcare Facilities (2008) Alcohol Overview. In the healthcare setting, “alcohol” refers to two water-soluble chemical compounds—ethyl alcohol and isopropyl alcohol —that have generally underrated germicidal characteristics 482. FDA has not cleared any liquid chemical sterilant or high- level disinfectant with alcohol as the main active ingredient. These alcohols are rapidly bactericidal rather than bacteriostatic against vegetative forms of bacteria; they also are tuberculocidal, fungicidal, and virucidal but do not destroy bacterial spores. Their cidal activity drops sharply when diluted below 50% concentration, and the optimum bactericidal concentration is 60%–90% solutions in water (volume/volume) 483, 484. Mode of Action. The most feasible explanation for the antimicrobial action of alcohol is denaturation of proteins. This mechanism is supported by the observation that absolute ethyl alcohol, a dehydrating agent, is less bactericidal than mixtures of alcohol and water because proteins are denatured more quickly in the presence of water 484, 485. Protein denaturation also is consistent with observations that alcohol destroys the dehydrogenases of Escherichia coli 486, and that ethyl alcohol increases the lag phase of Enterobacter aerogenes 487 and that the lag phase e!ect could be reversed by adding certain amino acids. The bacteriostatic action was believed caused by inhibition of the production of metabolites essential for rapid cell division. Microbicidal Activity. Methyl alcohol (methanol) has the weakest bactericidal action of the alcohols and thus seldom is used in healthcare 488. The bactericidal activity of various concentrations of ethyl alcohol (ethanol) was examined against a variety of microorganisms in exposure periods ranging from 10 seconds to 1 hour 483.
    [Show full text]
  • Guideline for Disinfection and Sterilization in Healthcare Facilities, 2008
    Guideline for Disinfection and Sterilization in Healthcare Facilities, 2008 Guideline for Disinfection and Sterilization in Healthcare Facilities, 2008 William A. Rutala, Ph.D., M.P.H.1,2, David J. Weber, M.D., M.P.H.1,2, and the Healthcare Infection Control Practices Advisory Committee (HICPAC)3 1Hospital Epidemiology University of North Carolina Health Care System Chapel Hill, NC 27514 2Division of Infectious Diseases University of North Carolina School of Medicine Chapel Hill, NC 27599-7030 1 Guideline for Disinfection and Sterilization in Healthcare Facilities, 2008 3HICPAC Members Robert A. Weinstein, MD (Chair) Cook County Hospital Chicago, IL Jane D. Siegel, MD (Co-Chair) University of Texas Southwestern Medical Center Dallas, TX Michele L. Pearson, MD (Executive Secretary) Centers for Disease Control and Prevention Atlanta, GA Raymond Y.W. Chinn, MD Sharp Memorial Hospital San Diego, CA Alfred DeMaria, Jr, MD Massachusetts Department of Public Health Jamaica Plain, MA James T. Lee, MD, PhD University of Minnesota Minneapolis, MN William A. Rutala, PhD, MPH University of North Carolina Health Care System Chapel Hill, NC William E. Scheckler, MD University of Wisconsin Madison, WI Beth H. Stover, RN Kosair Children’s Hospital Louisville, KY Marjorie A. Underwood, RN, BSN CIC Mt. Diablo Medical Center Concord, CA This guideline discusses use of products by healthcare personnel in healthcare settings such as hospitals, ambulatory care and home care; the recommendations are not intended for consumer use of the products discussed. 2
    [Show full text]
  • Compatible Cleaning Solutions Chart*
    Compatible Cleaning Solutions Chart* Reactive Chemicals Natural Rubber Polyurethane 316 Stainless Vinyl Nitrile FKM (Viton) Aluminum Neoprene Hypalon Silicone UHMW Hytrel Nitrile / SBR EPDM Nylon Brass XLPE Steel PTFE CPE Fluid PVC Notes: Alcohols +++++++–+–+– +++++ • Ingredient in Some (Methanol & Ethanol) Anti-Viral Cleansers Bleaching and Cleaning Bleach Solution + + • ••––– • + • – + • • – – – + – – Agent; Sodium (Sodium Hypochlorite) Hypochlorite Butyl Alcohol + + • + + + + + + + – + + + + + + + + + Potent virucidal agent Chlorine – – – – – – + + – – • • • Antiseptic; Anti-Viral – + + + + + ••– • + + • + + + + • + – – Insecticides and Citric Acid disinfectants; Antiviral Copper Chloride – + + + ••+++++++++++ +–– Copper Chloride Ethyl Alcohol + + + + + + + + • + • + + + + + + • + + + • + Ingredient in Some (Ethanol) Anti-Viral Cleansers Toilet, Tile and Porcelain Hydrochloric Acid +++–––––++–+++–––––– Cleaner; Anti-Viral (Polio) Hydrogen Peroxide + • – – – – – + • + – + • • – + • • ••–– Multipurpose Cleaner +++ –++–+––+ • ••–––– Antiseptic; Antiviral Iodine (Polio) + + + + ••+++–++++++++++++ Ingredient in Some Isopropyl Alcohol Anti-Viral Cleansers Phenol + • – – – – – – + – – + + + – – + + • + ••– Anti-Virus (Rhinovirus) (Carbolic Acid) (Adenovirus) Sodium Chloride ++++++++++++++++ • + – • Anti-Virus Sodium Hypochlorite ••+++––––++– • + + – – – ••–– Bleaching and Cleaning Agent (Bleach) Quaternary Ammonium + + + + + + + Common Anti-Viral; Salts (Lysol) Benzalkonium Chloride (Lysol) Lactic Acid – + • + – + + • + • • + + – + + + –
    [Show full text]
  • En Este Número
    Boletín Científico No. 18 (1-10 julio/2021) EN ESTE NÚMERO VacCiencia es una publicación dirigida a Resumen de candidatos vacu- investigadores y especialistas dedicados a nales contra la COVID-19 ba- la vacunología y temas afines, con el ob- sadas en la plataforma de sub- jetivo de serle útil. Usted puede realizar unidad proteica en desarrollo a sugerencias sobre los contenidos y de es- nivel mundial. (segunda parte) ta forma crear una retroalimentación Artículos científicos más que nos permita acercarnos más a sus recientes de Medline sobre necesidades de información. vacunas. Patentes más recientes en Patentscope sobre vacunas. Patentes más recientes en USPTO sobre vacunas. 1| Copyright © 2020. Todos los derechos reservados | INSTITUTO FINLAY DE VACUNAS Resumen de vacunas contra la COVID-19 basadas en la plataforma de subunidad proteica en desarrollo a nivel mundial (segunda parte) Las vacunas de subunidades antigénicas son aquellas en las que solamente se utilizan los fragmentos específicos (llamados «subunidades antigénicas») del virus o la bacteria que es indispensable que el sistema inmunitario reconozca. Las subunidades antigénicas suelen ser proteínas o hidratos de carbono. La mayoría de las vacunas que figuran en los calendarios de vacunación infantil son de este tipo y protegen a las personas de enfermedades como la tos ferina, el tétanos, la difteria y la meningitis meningocócica. Este tipo de vacunas solo incluye las partes del microorganismo que mejor estimulan al sistema inmunitario. En el caso de las desarrolladas contra la COVID-19 contienen generalmente, la proteína S o fragmentos de la misma como el Dominio de Unión al Receptor (RBD, por sus siglas en inglés).
    [Show full text]
  • US EPA, Pesticide Product Label, XHC-IA,06/07/2018
    UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON, DC 20460 OFFICE OF CHEMICAL SAFETY AND POLLUTION PREVENTION June 7, 2018 Bridget Middleton, M.S. Regulatory Specialist Ecolab Inc. 1 Ecolab Place St. Paul, MN 55102 Subject: PRIA Label Amendment – Adding Efficacy Claims and Emerging Viral Pathogens Language Product Name: XHC-IA EPA Registration Number: 1677-249 Application Date: January 16, 2018 Decision Number: 537595 Dear Ms. Middleton: The amended label referred to above, submitted in connection with registration under the Federal Insecticide, Fungicide and Rodenticide Act, as amended, is acceptable. This approval does not affect any conditions that were previously imposed on this registration. You continue to be subject to existing conditions on your registration and any deadlines connected with them. A stamped copy of your labeling is enclosed for your records. This labeling supersedes all previously accepted labeling. You must submit one copy of the final printed labeling before you release the product for shipment with the new labeling. In accordance with 40 CFR 152.130(c), you may distribute or sell this product under the previously approved labeling for 18 months from the date of this letter. After 18 months, you may only distribute or sell this product if it bears this new revised labeling or subsequently approved labeling. “To distribute or sell” is defined under FIFRA section 2(gg) and its implementing regulation at 40 CFR 152.3. Because you have opted to add statements pertaining to emerging viral pathogens to your label as described in the August 19, 2016, Guidance to Registrants: Process For Making Claims Against Emerging Viral Pathogens Not On EPA-Registered Disinfectant Labels (“Guidance”), https://www.epa.gov/sites/production/files/2016- 09/documents/emerging_viral_pathogen_program_guidance_final_8_19_16_001_0.pdf, you are subject to the following additional terms of registration: 1.
    [Show full text]
  • Heterologous Prime-Boost COVID-19 Vaccination: Initial Reactogenicity Data
    Correspondence Heterologous (100 participants with additional 24 (21%) of 112 recipients of BNT for prime-boost COVID-19 visits), at baseline (before the prime both prime and boost (difference 21%, dose), at day 28 (before the boost 95% CI 8–33%). Similar increases were Published Online vaccination: initial dose) and 7 days post-boost, graded observed for chills, fatigue, headache, May 12, 2021 https://doi.org/10.1016/ according to a modified US Food joint pain, malaise, and muscle ache reactogenicity data S0140-6736(21)01115-6 and Drug Administration toxicity (figure; appendix). There were no There is significant international scale (appendix). All analyses are hospitalisations due to solicited See Online for appendix interest in heterologous prime-boost descriptive, as the study was not symptoms, and most of this increase in COVID-19 vaccination to mitigate powered for reactogenicity, with reactogenicity was observed in the 48 h against supply shocks or shortages endpoints reported as frequencies and after immunisation (appendix). that might otherwise reduce the speed percentages, together with absolute Participants were advised that of vaccine roll-out. Additionally, in differences between heterologous and paracetamol might reduce vaccine light of changing recommendations homologous vaccine schedules and side-effects but were not actively coun- regarding use of the ChAdOx1 nCoV-19 corresponding 95% CIs. selled to medicate prophylactically. (ChAd) COVID-19 vaccine (Vaxzevria, Recruitment commenced on Paracetamol use in the 48 h post-boost AstraZeneca), several countries are now Feb 11, 2021, and was completed on vaccine was reported by 40 (36%) of advising that individuals previously Feb 26, 2021, with 830 participants 112 recipients of ChAd for both prime primed with this vaccine should now enrolled and randomised from and boost, 63 (57%) of 110 recipients receive an alternative vaccine as 978 screened (the CONSORT flow of ChAd for prime and BNT for boost, their second dose, most commonly diagram is available in the appendix).
    [Show full text]