COVID-19: Mechanisms of Vaccination and Immunity
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SARS-Cov-2 RBD219-N1C1 Was Diluted in 20 Mm Tris, 150 Mm Nacl, Ph 7.5 (TBS Buffer) Before
bioRxiv preprint doi: https://doi.org/10.1101/2020.11.04.367359; this version posted November 5, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Title Page SARS‑CoV-2 RBD219-N1C1: A Yeast-Expressed SARS-CoV-2 Recombinant Receptor-Binding Domain Candidate Vaccine Stimulates Virus Neutralizing Antibodies and T-cell Immunity in Mice 1 2 3 Jeroen Pollet1,2, Wen-Hsiang Chen1,2, Leroy Versteeg1, Brian Keegan1, Bin Zhan1,2, Junfei 4 Wei1, Zhuyun Liu1, Jungsoon Lee1, Rahki Kundu1, Rakesh Adhikari1, Cristina Poveda1, 5 Maria-Jose Villar Mondragon1, Ana Carolina de Araujo Leao1, Joanne Altieri Rivera1, Portia 6 M. Gillespie1, Ulrich Strych1,2, Peter J. Hotez1,2,3,4,*, Maria Elena Bottazzi1,2,3* 7 1 Texas Children’s Hospital Center for Vaccine Development, Houston, TX, USA 8 2 Departments of Pediatrics and Molecular Virology & Microbiology, National School of Tropical 9 Medicine, Baylor College of Medicine, Houston, TX, USA 10 3 Department of Biology, Baylor University, Waco, TX, USA 11 4 James A. Baker III Institute for Public Policy, Rice University, Houston, TX, USA 12 * Correspondence: 13 Corresponding Authors 14 [email protected]; [email protected] 15 16 bioRxiv preprint doi: https://doi.org/10.1101/2020.11.04.367359; this version posted November 5, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Yeast-expressed SARS-CoV-2 RBD 17 Abstract 18 There is an urgent need for an accessible and low-cost COVID-19 vaccine suitable for low- and 19 middle-income countries. -
Perspectives for Therapeutic HPV Vaccine Development Andrew Yang1†, Emily Farmer1†,T.C.Wu1,2,3,4 and Chien-Fu Hung1,4,5*
Yang et al. Journal of Biomedical Science (2016) 23:75 DOI 10.1186/s12929-016-0293-9 REVIEW Open Access Perspectives for therapeutic HPV vaccine development Andrew Yang1†, Emily Farmer1†,T.C.Wu1,2,3,4 and Chien-Fu Hung1,4,5* Abstract Background: Human papillomavirus (HPV) infections and associated diseases remain a serious burden worldwide. It is now clear that HPV serves as the etiological factor and biologic carcinogen for HPV-associated lesions and cancers. Although preventative HPV vaccines are available, these vaccines do not induce strong therapeutic effects against established HPV infections and lesions. These concerns create a critical need for the development of therapeutic strategies, such as vaccines, to treat these existing infections and diseases. Main Body: Unlike preventative vaccines, therapeutic vaccines aim to generate cell-mediated immunity. HPV oncoproteins E6 and E7 are responsible for the malignant progression of HPV-associated diseases and are consistently expressed in HPV-associated diseases and cancer lesions; therefore, they serve as ideal targets for the development of therapeutic HPV vaccines. In this review we revisit therapeutic HPV vaccines that utilize this knowledge to treat HPV-associated lesions and cancers, with a focus on the findings of recent therapeutic HPV vaccine clinical trials. Conclusion: Great progress has been made to develop and improve novel therapeutic HPV vaccines to treat existing HPV infections and diseases; however, there is still much work to be done. We believe that therapeutic HPV vaccines have the potential to become a widely available and successful therapy to treat HPV and HPV-associated diseases in the near future. -
Differentiation and Bone Resorption Role of CX3CL1/Fractalkine In
Role of CX3CL1/Fractalkine in Osteoclast Differentiation and Bone Resorption Keiichi Koizumi, Yurika Saitoh, Takayuki Minami, Nobuhiro Takeno, Koichi Tsuneyama, Tatsuro Miyahara, This information is current as Takashi Nakayama, Hiroaki Sakurai, Yasuo Takano, Miyuki of September 29, 2021. Nishimura, Toshio Imai, Osamu Yoshie and Ikuo Saiki J Immunol published online 18 November 2009 http://www.jimmunol.org/content/early/2009/11/18/jimmuno l.0803627.citation Downloaded from Why The JI? Submit online. http://www.jimmunol.org/ • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication *average by guest on September 29, 2021 Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. Published November 18, 2009, doi:10.4049/jimmunol.0803627 The Journal of Immunology Role of CX3CL1/Fractalkine in Osteoclast Differentiation and Bone Resorption1 Keiichi Koizumi,2* Yurika Saitoh,* Takayuki Minami,* Nobuhiro Takeno,* Koichi Tsuneyama,†‡ Tatsuro Miyahara,§ Takashi Nakayama,¶ Hiroaki Sakurai,*† Yasuo Takano,‡ Miyuki Nishimura,ʈ Toshio Imai,ʈ Osamu Yoshie,¶ and Ikuo Saiki*† The recruitment of osteoclast precursors toward osteoblasts and subsequent cell-cell interactions are critical for osteoclast dif- ferentiation. -
Gamma-Irradiated SARS-Cov-2 Vaccine Candidate, OZG-38.61.3, Confers Protection from SARS-Cov-2 Challenge in Human ACEII-Transgen
www.nature.com/scientificreports OPEN Gamma‑irradiated SARS‑CoV‑2 vaccine candidate, OZG‑38.61.3, confers protection from SARS‑CoV‑2 challenge in human ACEII‑transgenic mice Raife Dilek Turan1,2,19, Cihan Tastan1,3,4,19*, Derya Dilek Kancagi1,19, Bulut Yurtsever1,19, Gozde Sir Karakus1,19, Samed Ozer5, Selen Abanuz1,6, Didem Cakirsoy1,8, Gamze Tumentemur7, Sevda Demir2, Utku Seyis1, Recai Kuzay1, Muhammer Elek1,2, Miyase Ezgi Kocaoglu1, Gurcan Ertop7, Serap Arbak9, Merve Acikel Elmas9, Cansu Hemsinlioglu1, Ozden Hatirnaz Ng10, Sezer Akyoney10,11, Ilayda Sahin8,12, Cavit Kerem Kayhan13, Fatma Tokat14, Gurler Akpinar15, Murat Kasap15, Ayse Sesin Kocagoz16, Ugur Ozbek12, Dilek Telci2, Fikrettin Sahin2, Koray Yalcin1,17, Siret Ratip18, Umit Ince14 & Ercument Ovali1 The SARS‑CoV‑2 virus caused the most severe pandemic around the world, and vaccine development for urgent use became a crucial issue. Inactivated virus formulated vaccines such as Hepatitis A and smallpox proved to be reliable approaches for immunization for prolonged periods. In this study, a gamma‑irradiated inactivated virus vaccine does not require an extra purifcation process, unlike the chemically inactivated vaccines. Hence, the novelty of our vaccine candidate (OZG‑38.61.3) is that it is a non‑adjuvant added, gamma‑irradiated, and intradermally applied inactive viral vaccine. Efciency and safety dose (either 1013 or 1014 viral RNA copy per dose) of OZG‑38.61.3 was initially determined in BALB/c mice. This was followed by testing the immunogenicity and protective efcacy of the vaccine. Human ACE2‑encoding transgenic mice were immunized and then infected with the SARS‑CoV‑2 virus for the challenge test. -
Main Outcomes of Discussion of WHO Consultation on Nucleic Acid
MAIN OUTCOMES OF DISCUSSION FROM WHO CONSULTATION ON NUCLEIC ACID VACCINES I. Knezevic, R. Sheets 21-23 Feb, 2018 Geneva, Switzerland CONTEXT OF DISCUSSION • WHO Consultation held to determine whether the existing DNA guidelines were due for revision or if they remained relevant with today’s status of nucleic acid vaccine development and maturity towards licensure (marketing authorization) • Presentation will cover alignment to existing guidelines • Current status of development of DNA and RNA vaccines, both prophylactic & therapeutic • Main outcomes of discussion • Next steps already underway & planned STATUS OF DEVELOPMENT OF NUCLEIC ACID VACCINES • First likely candidate to licensure could be a therapeutic DNA vaccine against Human Papilloma Viruses • Anticipated to be submitted for licensure in 3-5 years • Other DNA vaccines are likely to follow shortly thereafter, e.g., Zika prophylaxis • RNA vaccines – less clinical experience, but therapeutic RNAs anticipated in 2021/22 timeframe to be submitted for licensure • For priority pathogens in context of public health emergencies, several candidates under development (e.g., MERS-CoV, Marburg, Ebola) MAIN OUTCOMES - GENERAL • Regulators expressed need for updated DNA guideline for prophylaxis and therapy • Less need at present for RNA vaccines in guideline but need some basic PTC • Flexibility needed now until more experience gained for RNA vaccines that will come in next few years • Revisit need for a more specific guideline at appropriate time for RNA vaccines • Institutional Biosafety Committees are regulated by national jurisdictions & vary considerably • How can WHO assist to streamline or converge these review processes? Particularly, during Public Health Emergency – can anything be done beforehand? MAIN OUTCOMES - DEFINITIONS • Clear Definitions are needed • Proposed definition of DNA vaccine: • A DNA plasmid(s) into which the desired immunogen(s) is (are) encoded and prepared as purified plasmid preparations to be administered in vivo. -
CLINICAL TRIALS Safety and Immunogenicity of a Nicotine Conjugate Vaccine in Current Smokers
CLINICAL TRIALS Safety and immunogenicity of a nicotine conjugate vaccine in current smokers Immunotherapy is a novel potential treatment for nicotine addiction. The aim of this study was to assess the safety and immunogenicity of a nicotine conjugate vaccine, NicVAX, and its effects on smoking behavior. were recruited for a noncessation treatment study and assigned to 1 of 3 doses of the (68 ؍ Smokers (N nicotine vaccine (50, 100, or 200 g) or placebo. They were injected on days 0, 28, 56, and 182 and monitored for a period of 38 weeks. Results showed that the nicotine vaccine was safe and well tolerated. Vaccine immunogenicity was dose-related (P < .001), with the highest dose eliciting antibody concentrations within the anticipated range of efficacy. There was no evidence of compensatory smoking or precipitation of nicotine withdrawal with the nicotine vaccine. The 30-day abstinence rate was significantly different across with the highest rate of abstinence occurring with 200 g. The nicotine vaccine appears ,(02. ؍ the 4 doses (P to be a promising medication for tobacco dependence. (Clin Pharmacol Ther 2005;78:456-67.) Dorothy K. Hatsukami, PhD, Stephen Rennard, MD, Douglas Jorenby, PhD, Michael Fiore, MD, MPH, Joseph Koopmeiners, Arjen de Vos, MD, PhD, Gary Horwith, MD, and Paul R. Pentel, MD Minneapolis, Minn, Omaha, Neb, Madison, Wis, and Rockville, Md Surveys show that, although about 41% of smokers apy, is about 25% on average.2 Moreover, these per- make a quit attempt each year, less than 5% of smokers centages most likely exaggerate the efficacy of are successful at remaining abstinent for 3 months to a intervention because these trials are typically composed year.1 Smokers seeking available behavioral and phar- of subjects who are highly motivated to quit and who macologic therapies can enhance successful quit rates are free of complicating diagnoses such as depression 2 by 2- to 3-fold over control conditions. -
Program Evaluation Key Outcomes and Addressing Remaining
Vaccine 31S (2013) J73–J78 Contents lists available at ScienceDirect Vaccine jou rnal homepage: www.elsevier.com/locate/vaccine Key outcomes and addressing remaining challenges—Perspectives from a final ଝ evaluation of the China GAVI project a,1 a,1 a,1 a,1 b c Weizhong Yang , Xiaofeng Liang , Fuqiang Cui , Li Li , Stephen C. Hadler , Yvan J. Hutin , d a,∗ Mark Kane , Yu Wang a Chinese Center for Disease Control and Prevention, Beijing, China b Centers for Disease Control and Prevention, Atlanta, USA c Europe Center for Disease Control and Prevention, Stockholm, Sweden d Mercer Island, Washington, USA a r t a b i c s t l r e i n f o a c t Article history: During the China GAVI project, implemented between 2002 and 2010, more than 25 million children Received 6 June 2012 received hepatitis B vaccine with the support of project, and the vaccine proved to be safe and effective. Received in revised form 24 July 2012 With careful consideration for project savings, China and GAVI continually adjusted the budget, addi- Accepted 24 September 2012 tionally allowing the project to spend operational funds to support demonstration projects to improve timely birth dose (TBD), conduct training of EPI staff, and to monitor the project impact. Results from the final evaluation indicated the achievement of key outcomes. As a result of government co-investment, Keywords: human resources at county level engaged in hepatitis B vaccination increased from 29 per county on GAVI Project average in 2002 to 66 in 2009. All project counties funded by the GAVI project use auto-disable syringes Outcomes for hepatitis B vaccination and other vaccines. -
COVID-19 Natural Immunity
COVID-19 natural immunity Scientific brief 10 May 2021 Key Messages: • Within 4 weeks following infection, 90-99% of individuals infected with the SARS-CoV-2 virus develop detectable neutralizing antibodies. • The strength and duration of the immune responses to SARS-CoV-2 are not completely understood and currently available data suggests that it varies by age and the severity of symptoms. Available scientific data suggests that in most people immune responses remain robust and protective against reinfection for at least 6-8 months after infection (the longest follow up with strong scientific evidence is currently approximately 8 months). • Some variant SARS-CoV-2 viruses with key changes in the spike protein have a reduced susceptibility to neutralization by antibodies in the blood. While neutralizing antibodies mainly target the spike protein, cellular immunity elicited by natural infection also target other viral proteins, which tend to be more conserved across variants than the spike protein. The ability of emerging virus variants (variants of interest and variants of concern) to evade immune responses is under investigation by researchers around the world. • There are many available serologic assays that measure the antibody response to SARS-CoV-2 infection, but at the present time, the correlates of protection are not well understood. Objective of the scientific brief This scientific brief replaces the WHO Scientific Brief entitled “’Immunity passports’ in the context of COVID-19”, published 24 April 2020.1 This update is focused on what is currently understood about SARS-CoV-2 immunity from natural infection. More information about considerations on vaccine certificates or “passports”will be covered in an update of WHO interim guidance, as requested by the COVID-19 emergency committee.2 Methods A rapid review on the subject was undertaken and scientific journals were regularly screened for articles on COVID-19 immunity to ensure to include all large and robust studies available in the literature at the time of writing. -
The Hepatitis B Vaccine Is the Most Widely Used Vaccine in the World, with Over 1 Billion Doses Given
Hepatitis B Vaccine Protect Yourself and Those You Love What is Hepatitis B? Hepatitis B is the most common serious liver infection in the world. It is caused by the hepatitis B virus (HBV), which attacks liver cells and can lead to liver failure, cirrhosis (scarring), or liver cancer later in life. The virus is transmitted through direct contact with infected blood and bodily fluids, and from an infected woman to her newborn at birth. Is there a safe vaccine for hepatitis B? YES! The good news is that there is a safe and effective vaccine for hepatitis B. The vaccine is a series, typically given as three shots over a six-month period that will provide a lifetime of protection. You cannot get hepatitis B from the vaccine – there is no human blood or live virus in the vaccine. The hepatitis B vaccine is the most widely used vaccine in the world, with over 1 billion doses given. The hepatitis B vaccine is the first "anti-cancer" vaccine because it can help prevent liver cancer! Who should be vaccinated against hepatitis B? The World Health Organization (WHO) and the U.S. Centers for Disease Control and Prevention (CDC) recommend the hepatitis B vaccine for all newborns and children up to 18 years of age, and all high-risk adults. All infants should receive the first dose of the vaccine in the delivery room or in the first 24 hours of life, preferably within 12 hours. (CDC recommends the first dose within 12 hours vs. the WHO recommendation of 24 hours.) The HBV vaccine is recommended to anyone who is at high risk of infection. -
(ACIP) General Best Guidance for Immunization
8. Altered Immunocompetence Updates This section incorporates general content from the Infectious Diseases Society of America policy statement, 2013 IDSA Clinical Practice Guideline for Vaccination of the Immunocompromised Host (1), to which CDC provided input in November 2011. The evidence supporting this guidance is based on expert opinion and arrived at by consensus. General Principles Altered immunocompetence, a term often used synonymously with immunosuppression, immunodeficiency, and immunocompromise, can be classified as primary or secondary. Primary immunodeficiencies generally are inherited and include conditions defined by an inherent absence or quantitative deficiency of cellular, humoral, or both components that provide immunity. Examples include congenital immunodeficiency diseases such as X- linked agammaglobulinemia, SCID, and chronic granulomatous disease. Secondary immunodeficiency is acquired and is defined by loss or qualitative deficiency in cellular or humoral immune components that occurs as a result of a disease process or its therapy. Examples of secondary immunodeficiency include HIV infection, hematopoietic malignancies, treatment with radiation, and treatment with immunosuppressive drugs. The degree to which immunosuppressive drugs cause clinically significant immunodeficiency generally is dose related and varies by drug. Primary and secondary immunodeficiencies might include a combination of deficits in both cellular and humoral immunity. Certain conditions like asplenia and chronic renal disease also can cause altered immunocompetence. Determination of altered immunocompetence is important to the vaccine provider because incidence or severity of some vaccine-preventable diseases is higher in persons with altered immunocompetence; therefore, certain vaccines (e.g., inactivated influenza vaccine, pneumococcal vaccines) are recommended specifically for persons with these diseases (2,3). Administration of live vaccines might need to be deferred until immune function has improved. -
Acting on the CCR1 Receptor Mediates Neutrophil Migration in Immune Inflammation Via Sequential ␣ Release of TNF- and LTB4 Cleber D
MIP-1␣[CCL3] acting on the CCR1 receptor mediates neutrophil migration in immune inflammation via sequential ␣ release of TNF- and LTB4 Cleber D. L. Ramos,* Claudio Canetti,*,† Janeusa T. Souto,‡,§ Joa˜ o S. Silva,‡ Cory M. Hogaboam,¶ Sergio H. Ferreira,* and Fernando Q. Cunha*,1 Departments of *Pharmacology and ‡Biochemistry and Immunology, School of Medicine of Ribeira˜o Preto, University of Sa˜o Paulo, Brazil; §Department of Microbiology and Parasitology, Federal University of Rio Grande do Norte, Natal, RN, Brazil; and †Division of Pulmonary & Critical Care Medicine and ¶Department of Pathology, University of Michigan, Ann Arbor Abstract: In the present study, we investigated nists might have a therapeutic potential. J. Leukoc. the involvement of macrophage-inflammatory pro- Biol. 78: 167–177; 2005. tein-1␣ (MIP-1␣)[CC chemokine ligand 3 (CCL3)], MIP-1[CCL4], regulated on activation, normal Key Words: chemokines ⅐ chemokine receptors ⅐ chemotaxis T expressed and secreted (RANTES)[CCL5], and CC chemokine receptors (CCRs) on neutrophil mi- gration in murine immune inflammation. Previ- INTRODUCTION ously, we showed that ovalbumin (OVA)-triggered neutrophil migration in immunized mice depends on the sequential release of tumor necrosis factor Neutrophil migration is a complex process, which results ␣ ␣ mainly from the release of neutrophil chemotactic factors by (TNF- ) and leukotriene B4 (LTB4). Herein, we show increased mRNA expression for MIP- resident cells, inducing rolling and adhesion of neutrophils on 1␣[CCL3], MIP-1[CCL4], RANTES[CCL5], and endothelial cells, followed by their transmigration to the ex- travascular space [1, 2]. Apart from its importance in host CCR1 in peritoneal cells harvested from OVA-chal- defense, the migration of neutrophils to the inflammatory site lenged, immunized mice, as well as MIP-1␣[CCL3] is, at least in part, responsible for tissue damage observed in and RANTES[CCL5] but not MIP-1[CCL4] proteins several inflammatory diseases such as rheumatoid arthritis, in the peritoneal exudates. -
Different Types of COVID-19 Vaccines
Pfizer-BioNTech Help stop the pandemic Type of vaccine: Messenger RNA, or mRNA, a genetic Different Types material that tells your body how to make proteins that by getting vaccinated triggers an immune response inside our bodies of COVID-19 Effectiveness: 95% based on clinical trials Even if you are undocumented Common side effects: Pain and/or swelling in the arm and/or don’t have insurance, you and tiredness, headache, muscle pain, chills, fever, or can get the vaccine—for free. Vaccines: nausea in the body that may last two days Recommended Ages: 16 and older (currently testing the vaccine in kids ages 12-15) Understanding How Dosage: Two shots, 21 days apart They Work Visit VaccinateALL58.com Moderna for the newest information about when and where the vaccine Type of vaccine: Messenger RNA, or mRNA, a genetic will be available to you. material that tells your body how to make proteins that triggers an immune response inside our bodies Sign up at myturn.ca.gov or Effectiveness: 94.1% based on clinical trials call 1-833-422-4255 to find out Common side effects: Pain and/or swelling in the arm if it’s your turn to get vaccinated and and tiredness, headache, muscle pain, chills, fever, or schedule vaccination appointments. nausea in the body that may last two days Recommended Ages: 18 years and older (currently testing the vaccine in kids ages 12-17) Dosage: Two shots, 28 days apart Johnson & Johnson Follow us on social media for more COVID-19 tips and information. Type of vaccine: A viral vector, it uses a harmless version of a different