Researchers Investigating Influence of Sex Hormones on HIV Cure Strategies

Link Type
Funded-research
Media Type
Article
Publish or Event Date
Link URL
https://smhs.gwu.edu/news/researchers-investigating-influence-sex-hormones-hiv-cure-strategies
Research Institution
GW School of Medicine and Health Sciences
Short Title
Researchers Investigating Influence of Sex Hormones on HIV Cure Strategies
Content Coordinator
Claudia Wair
Content Manager
Kathy Donbeck

International Team of Scientists Identifies Common Vulnerabilities Across Coronaviruses

Link Type
Funded-research
Media Type
Article
Publish or Event Date
Link URL
https://www.ucsf.edu/news/2020/10/418796/international-team-scientists-identifies-common-vulnerabilities-across
Research Institution
University of California San Francisco
Short Title
International Team of Scientists Identifies Common Vulnerabilities Across Coronaviruses
Content Coordinator
Claudia Wair
Content Manager
Kathy Donbeck

Ursula Buchholz, Ph.D.

Chief, RNA Viruses Section
Contact Information
Ursula Buchholz, Ph.D.
Ursula Buchholz, Ph.D.
Ursula Buchholz, Ph.D.
Credit
NIAID

Major Areas of Research

  • Studies of molecular biology, immunobiology, and pathogenesis of the human respiratory pathogens respiratory syncytial virus (RSV), human parainfluenza virus (HPIV) serotypes 1, 2, and 3, and human metapneumovirus (HMPV)
    • Studies involve infection in vitro of epithelial cells, macrophages, and other cell types and in vivo infection of experimental animals to elucidate the viral replicative cycle, interactions between viral and host components, the host response to infection, and mechanisms of pathogenesis.
  • Development of live-attenuated RSV, HPIV3, and HMPV vaccine candidates
    • Vaccine candidates are designed to contain well-defined attenuating mutations and are generated from cDNA by “reverse genetics”. Candidates are evaluated preclinically in monolayer cell cultures, in vitro models of airway epithelium, rodents, and nonhuman primates.
  • Evaluation of candidate live vaccines in clinical studies with clinical collaborators, as well as wild type viruses in adult volunteers
  • Development of vaccine vectors based on HPIV and avian paramyxoviruses (APMVs) for use against highly pathogenic emerging viruses including SARS Coronavirus 2, avian influenza, and Ebola viruses

Program Description

We study the molecular virology, pathogenesis, and immune response of human respiratory pathogens, including RSV, HPIV serotypes 1, 2, and 3, and HMPV. These are enveloped, cytoplasmic viruses with single-stranded negative-sense RNA genomes of 13-19 kb. The laboratory investigates basic features of viral molecular biology, pathogenesis, and immunobiology of these viruses that provide an intellectual foundation for translational vaccine studies.

The pneumovirus RSV is a leading worldwide agent of respiratory tract disease, especially in young infants. The laboratory also studies several other major pediatric respiratory pathogens, namely HPIV1, 2, and 3 and HMPV. Other areas of interest include other pathogens of the paramyxoviridae and pneumoviridae families. The laboratory is using reverse genetics to design live, attenuated vaccines for RSV, HPIV3, and HMPV for intranasal administration to infants as pediatric vaccines. In studies supported in part by collaboration with industry, lead candidates for RSV and HPIV3 are in Phase I, and in some cases Phase II, clinical trials. The laboratory also is using paramyxoviruses and pneumoviruses as vaccine vectors to express protective antigens of emerging pathogens. In 2020, we expanded our program to include the development of vector vaccine candidates against SARS-CoV-2.

Biography

Dr. Buchholz received her Ph.D. in 1994 from the Free University of Berlin, Germany. She conducted postdoctoral studies at the Federal Research Center of Virus Diseases of Animals in Tuebingen, Germany, and became a tenured scientist at the Federal Research Center in 2000. In 2002, she joined Dr. Peter L. Collins’ section in the Laboratory of Infectious Diseases, and she became the Chief of the RNA Viruses Section in 2020.

Memberships

  • American Society for Virology
  • American Society for Microbiology
  • International RSV Society
  • Pneumoviridae study group, International Committee on Taxonomy of Viruses

Research Group

Laura Ahlers, Sharmin Afroz, Sonja Barbagallo, Bibha Dahal, Jaclyn Kaiser, Cyril Le Nouen, Xueqiao Liu, Cindy Luongo, Thomas McCarty, Shirin Munir, Hongsu Park, Celia Santos, Lijuan Yang, Jessica Chen, Megan Levy, Jana Liese

Selected Publications

Karron RA, Luongo C, Mateo JS, Wanionek K, Collins PL, Buchholz UJ. Safety and Immunogenicity of the Respiratory Syncytial Virus Vaccine RSV/DeltaNS2/Delta1313/I1314L in RSV-Seronegative Children. J Infect Dis. 2020 Jun;222(1):82-91.

McFarland EJ, Karron RA, Muresan P, Cunningham CK, Libous J, Perlowski C, Thumar B, Gnanashanmugam D, Moye J, Schappell E, Barr E, Rexroad V, Fearn L, Spector SA, Aziz M, Cielo M, Beneri C, Wiznia A, Luongo C, Collins P, Buchholz UJ. Live Respiratory Syncytial Virus Attenuated by M2-2 Deletion and Stabilized Temperature Sensitivity Mutation 1030s Is a Promising Vaccine Candidate in Children. J Infect Dis. 2020 Feb;221(4):534-543.

Lingemann M, McCarty T, Liu X, Buchholz UJ, Surman S, Martin SE, Collins PL, Munir S. The alpha-1 subunit of the Na+,K+-ATPase (ATP1A1) is required for macropinocytic entry of respiratory syncytial virus (RSV) in human respiratory epithelial cells. PLoS Pathog. 2019 Aug;15(8):e1007963.

Le Nouën C, McCarty T, Brown M, Smith ML, Lleras R, Dolan MA, Mehedi M, Yang L, Luongo C, Liang B, Munir S, DiNapoli JM, Mueller S, Wimmer E, Collins PL, Buchholz UJ. Genetic stability of genome-scale deoptimized RNA virus vaccine candidates under selective pressure. Proc Natl Acad Sci USA. 2017 Jan;114(3):E386-E95.

Karron RA, Luongo C, Thumar B, Loehr KM, Englund JA, Collins PL, Buchholz UJ. A gene deletion that up-regulates viral gene expression yields an attenuated RSV vaccine with improved antibody responses in children. Sci Transl Med. 2015 Nov;7(312):312ra175.

Le Nouën C, Hillyer P, Winter CC, McCarty T, Rabin RL, Collins PL, Buchholz UJ. Low CCR7-mediated migration of human monocyte derived dendritic cells in response to human respiratory syncytial virus and human metapneumovirus. PLoS Pathog. 2011 Jun;7(6):e1002105.

Visit PubMed for a complete publication listing.

Patents

Le Nouen C, Buchholz UJ, Collins PL, Mueller S, inventors; The United States of America as represented by the Secretary, Department of Health and Human Services and Codagenix, Inc., assignees. Vaccine candidates for human respiratory syncytial virus (RSV) having attenuated phenotypes. United States patent US 10,808,012. 20 Oct 2020.

Collins, PL, Luongo, C, Buchholz UJ, inventors; The United States of America as represented by the Secretary, Department of Health and Human Services, assignee. Recombinant Respiratory Syncytial Virus Strains with Mutations in the M2-2 ORF Providing a Range of Attenuation Phenotypes. United States Patent no. US 10,655,109. 19 May 2020.

Collins, PL, Liang, B, Munir, S, Schaap-Nutt, A, Buchholz UJ, Mackow, N, Kwong, P, Graham B, McLellan, J, inventors; The United States of America as represented by the Secretary, Department of Health and Human Services, assignee. Recombinant Bovine/Human Parainfluenza Virus 3 (B/HPIV3) Expressing a Chimeric RSV/BPIV3 F Protein and Uses Thereof. United States Patent no. US 10,654,898. 19 May 2020.

Collins, PL, Luongo, C, Buchholz UJ, Murphy, BR, inventors; The United States of America as represented by the Secretary, Department of Health and Human Services, assignee. Genetically stable live attenuated respiratory syncytial virus vaccine and its production. United States Patent no. US 10,307,476. 4 June 2019.

Buchholz U, Collins PL, Murphy BR, Whitehead SS, Krempl CD, inventors; The United States of America as represented by the Secretary, Department of Health and Human Services, assignee. Production of attenuated, human-bovine chimeric respiratory syncytial virus vaccines. United States patent US 7,842,798. 30 Nov 2010.

Krempl CD, Collins PL, Murphy BR, Buchholz U, Whitehead SS, inventors; The United States of America as represented by the Department of Health and Human Services, assignee. Respiratory syncytial virus vaccines expressing protective antigens from promotor-proximal genes. United States patent US 7,744,902. 29 Jun 2010.

Visit the U.S. Patent and Trademark Office for a complete patent listing.

Section or Unit Name
RNA Viruses Section
Lab/Program Name
Laboratory of Infectious Diseases
First Name
Ursula
Last Name
Buchholz
Suffix
Ph.D.
Exclude from directory
Off
This Researcher/Clinician’s Person Page
Ursula Buchholz, Ph.D.
Parent Lab/Program
Laboratory of Infectious Diseases
Program Description

We study the molecular virology, pathogenesis, and immune response of human respiratory pathogens, including RSV, HPIV serotypes 1, 2, and 3, and HMPV. These are enveloped, cytoplasmic viruses with single-stranded negative-sense RNA genomes of 13-19 kb. The laboratory investigates basic features of viral molecular biology, pathogenesis, and immunobiology of these viruses that provide an intellectual foundation for translational vaccine studies.

The pneumovirus RSV is a leading worldwide agent of respiratory tract disease, especially in young infants. The laboratory also studies several other major pediatric respiratory pathogens, namely HPIV1, 2, and 3 and HMPV. Other areas of interest include other pathogens of the paramyxoviridae and pneumoviridae families. The laboratory is using reverse genetics to design live, attenuated vaccines for RSV, HPIV3, and HMPV for intranasal administration to infants as pediatric vaccines. In studies supported in part by collaboration with industry, lead candidates for RSV and HPIV3 are in Phase I, and in some cases Phase II, clinical trials. The laboratory also is using paramyxoviruses and pneumoviruses as vaccine vectors to express protective antigens of emerging pathogens. In 2020, we expanded our program to include the development of vector vaccine candidates against SARS-CoV-2.

Selected Publications

Karron RA, Luongo C, Mateo JS, Wanionek K, Collins PL, Buchholz UJ. Safety and Immunogenicity of the Respiratory Syncytial Virus Vaccine RSV/DeltaNS2/Delta1313/I1314L in RSV-Seronegative Children. J Infect Dis. 2020 Jun;222(1):82-91.

McFarland EJ, Karron RA, Muresan P, Cunningham CK, Libous J, Perlowski C, Thumar B, Gnanashanmugam D, Moye J, Schappell E, Barr E, Rexroad V, Fearn L, Spector SA, Aziz M, Cielo M, Beneri C, Wiznia A, Luongo C, Collins P, Buchholz UJ. Live Respiratory Syncytial Virus Attenuated by M2-2 Deletion and Stabilized Temperature Sensitivity Mutation 1030s Is a Promising Vaccine Candidate in Children. J Infect Dis. 2020 Feb;221(4):534-543.

Lingemann M, McCarty T, Liu X, Buchholz UJ, Surman S, Martin SE, Collins PL, Munir S. The alpha-1 subunit of the Na+,K+-ATPase (ATP1A1) is required for macropinocytic entry of respiratory syncytial virus (RSV) in human respiratory epithelial cells. PLoS Pathog. 2019 Aug;15(8):e1007963.

Le Nouën C, McCarty T, Brown M, Smith ML, Lleras R, Dolan MA, Mehedi M, Yang L, Luongo C, Liang B, Munir S, DiNapoli JM, Mueller S, Wimmer E, Collins PL, Buchholz UJ. Genetic stability of genome-scale deoptimized RNA virus vaccine candidates under selective pressure. Proc Natl Acad Sci USA. 2017 Jan;114(3):E386-E95.

Karron RA, Luongo C, Thumar B, Loehr KM, Englund JA, Collins PL, Buchholz UJ. A gene deletion that up-regulates viral gene expression yields an attenuated RSV vaccine with improved antibody responses in children. Sci Transl Med. 2015 Nov;7(312):312ra175.

Le Nouën C, Hillyer P, Winter CC, McCarty T, Rabin RL, Collins PL, Buchholz UJ. Low CCR7-mediated migration of human monocyte derived dendritic cells in response to human respiratory syncytial virus and human metapneumovirus. PLoS Pathog. 2011 Jun;7(6):e1002105.

Visit PubMed for a complete publication listing.

Additional Information

Research Group

Laura Ahlers, Sharmin Afroz, Sonja Barbagallo, Bibha Dahal, Jaclyn Kaiser, Cyril Le Nouen, Xueqiao Liu, Cindy Luongo, Thomas McCarty, Shirin Munir, Hongsu Park, Celia Santos, Lijuan Yang, Jessica Chen, Megan Levy, Jana Liese

Patents

Le Nouen C, Buchholz UJ, Collins PL, Mueller S, inventors; The United States of America as represented by the Secretary, Department of Health and Human Services and Codagenix, Inc., assignees. Vaccine candidates for human respiratory syncytial virus (RSV) having attenuated phenotypes. United States patent US 10,808,012. 20 Oct 2020.

Collins, PL, Luongo, C, Buchholz UJ, inventors; The United States of America as represented by the Secretary, Department of Health and Human Services, assignee. Recombinant Respiratory Syncytial Virus Strains with Mutations in the M2-2 ORF Providing a Range of Attenuation Phenotypes. United States Patent no. US 10,655,109. 19 May 2020.

Collins, PL, Liang, B, Munir, S, Schaap-Nutt, A, Buchholz UJ, Mackow, N, Kwong, P, Graham B, McLellan, J, inventors; The United States of America as represented by the Secretary, Department of Health and Human Services, assignee. Recombinant Bovine/Human Parainfluenza Virus 3 (B/HPIV3) Expressing a Chimeric RSV/BPIV3 F Protein and Uses Thereof. United States Patent no. US 10,654,898. 19 May 2020.

Collins, PL, Luongo, C, Buchholz UJ, Murphy, BR, inventors; The United States of America as represented by the Secretary, Department of Health and Human Services, assignee. Genetically stable live attenuated respiratory syncytial virus vaccine and its production. United States Patent no. US 10,307,476. 4 June 2019.

Buchholz U, Collins PL, Murphy BR, Whitehead SS, Krempl CD, inventors; The United States of America as represented by the Secretary, Department of Health and Human Services, assignee. Production of attenuated, human-bovine chimeric respiratory syncytial virus vaccines. United States patent US 7,842,798. 30 Nov 2010.

Krempl CD, Collins PL, Murphy BR, Buchholz U, Whitehead SS, inventors; The United States of America as represented by the Department of Health and Human Services, assignee. Respiratory syncytial virus vaccines expressing protective antigens from promotor-proximal genes. United States patent US 7,744,902. 29 Jun 2010.

Visit the U.S. Patent and Trademark Office for a complete patent listing.

Major Areas of Research
  • Studies of molecular biology, immunobiology, and pathogenesis of the human respiratory pathogens respiratory syncytial virus (RSV), human parainfluenza virus (HPIV) serotypes 1, 2, and 3, and human metapneumovirus (HMPV)
    • Studies involve infection in vitro of epithelial cells, macrophages, and other cell types and in vivo infection of experimental animals to elucidate the viral replicative cycle, interactions between viral and host components, the host response to infection, and mechanisms of pathogenesis.
  • Development of live-attenuated RSV, HPIV3, and HMPV vaccine candidates
    • Vaccine candidates are designed to contain well-defined attenuating mutations and are generated from cDNA by “reverse genetics”. Candidates are evaluated preclinically in monolayer cell cultures, in vitro models of airway epithelium, rodents, and nonhuman primates.
  • Evaluation of candidate live vaccines in clinical studies with clinical collaborators, as well as wild type viruses in adult volunteers
  • Development of vaccine vectors based on HPIV and avian paramyxoviruses (APMVs) for use against highly pathogenic emerging viruses including SARS Coronavirus 2, avian influenza, and Ebola viruses

AccessClinicalData@NIAID

NIAID Clinical Trials Data Repository, AccessClinicalData@NIAID, is an NIAID cloud-based, secure data platform that enables sharing of and access to anonymized individual, patient level clinical data sets from NIAID sponsored clinical trials to harness the power of data to generate new knowledge to understand, treat, and prevent infectious diseases such as COVID-19.

Steps to access clinical data can be found at Accessing Clinical Data.

Accessing Clinical Data

Request Access to the Data

Visit AccessClinicalData@NIAID to review and request access to NIAID Clinical Trials data.

Main Area of Focus

Allow the research community access to clinical data sets to harness the power of data to generate new knowledge to understand, treat, and prevent infectious diseases such as COVID-19.

Contact Information

Contact accessclinicaldatasupport@niaid.nih.gov for questions or help.

Data Management and Sharing Guidelines

NIAID provides guidance on data-management and -sharing practices to ensure NIAID’s research adheres to NIH policies to serve knowledge sharing, secondary use, and reproducibility of NIAID-funded research data as well as enable opportunities to develop a data science workforce. 

Read the Data Management and Sharing Guidelines
Publications

Baricitinib plus Remdesivir for Hospitalized Adults with Covid-19, New England Journal of Medicine, December 11, 2020

Remdesivir for the Treatment of Covid-19 — Final Report, New England Journal of Medicine, November 5, 2020

 

Content Coordinator
Maria Giovanni
Mason Booth
Cynthia Rojas
Content Manager
Alex Rosenthal
Introduction

NIAID Clinical Trials Data Repository, AccessClinicalData@NIAID, is an NIAID cloud-based, secure data platform that enables sharing of and access to reports and data sets from NIAID COVID-19 and other sponsored clinical trials for the basic and clinical research community.

Biomedical and health data coupled with powerful advanced data analytical and statistical tools provide innovative opportunities to accelerate the development of new and improved therapeutic interventions and diagnostics, improved prevention strategies and disease surveillance, and implement new and improved design of clinical trials. 

This NIAID research resource provides a foundation with potential to improve the health of people in the United States and around the world.

A red and yellow image of the novel coronavirus on a black background.
A transmission electron micrograph of the novel coronavirus SARS-CoV-2
Credit
NIAID

New Data Sets

Accessclinicaldata@NIAID has a new data set available from ACTIV-1 (Accelerating COVID-19 Therapeutics, Interventions and Vaccines) Clinical Trial sponsored by the U.S. Department of Health and Human Services Biomedical Advanced Research and Development Authority and the National Center for Advancing Translational Sciences, National Institutes of Health.

Centers for Medical Countermeasures Against Radiation Consortium

The Medical Countermeasures against Radiation Consortium (CMCRC) is a network of national research centers working together to develop effective and comprehensive medical countermeasures applicable to all subsets of the civilian population in the event of radiological or nuclear emergencies. They utilize multidisciplinary basic and translational research to support the development of new medical products that will assess, diagnose, mitigate and/or treat the short- and long-term consequences of radiation exposure after a radiological/nuclear terrorist event or accidental exposure. This research program was originally established by NIAID in 2005 under RFA-AI-04-045 and has been reissued three more times: 2010 (RFA-AI-09-036), 2015(RFA-AI-14-055), and 2020 (RFA-AI-19-012).

Main Areas of Focus

  • Produce new techniques and devices to measure radiation exposure in the human body
  • Follow biomarkers of tissue damage and recovery
  • Develop novel therapies to minimize tissue damage, hasten tissue recovery, restore normal physiological function, and improve survival

CMCRC Radiobiology Textbook

The CMCRC Radiobiology Textbook is a Radiobiology Methods “virtual textbook” that aims to provide the general scientific and educational community with a clear overview of radiation biology and dosimetry and inform readers about new advances in radiobiology.

Oversight

Radiation and Nuclear Countermeasures Program (RNCP)

Contact Information

Content Coordinator
Venera Barsaku
Content Manager
Adelina Bartels
Catherine Bullis

Administrative Supplements to Existing NIH Grants and Cooperative Agreements (Parent Admin Supp Clinical Trial Optional)

The National Institutes of Health (NIH) hereby notify Program Directors/Principal Investigators (PD(s)/PI(s)) holding specific types of NIH research grants listed in the full Notice of Funding Opportunity (NOFO) that funds may be available for administrative supplements to meet increased costs that are within the scope of the approved award, but were unforeseen when the new or renewal application or grant progress report for non-competing continuation support was submitted.

Volunteer for COVID-19 Clinical Trials

We made history with safe and effective vaccines and we’ll keep working as long as there are people to protect, variants emerging, and research answers needed to keep us all safe. That means we still need you!

NIAID is conducting and supporting clinical trials evaluating therapies and vaccine candidates against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19), as well as studies of people who have recovered from infection.

Featured COVID-19 Studies

Cartoon of a man getting an infusion
Credit
HHS

Outpatient Treatment With Anti-Coronavirus Immunoglobulin (OTAC)

A research study testing an experimental COVID-19 treatment called anti-coronavirus hyperimmune intravenous immunoglobulin (hIVIG).

Tratamiento ambulatorio con inmunoglobulina anticoronavirus

Ongoing NIAID-supported COVID-19 Studies

Browse a selection of NIAID-supported studies. A frequently updated, comprehensive list of all COVID-19 clinical trials can be found on ClinicalTrials.gov.

Find COVID-19 Clinical Trials

 

Centers for Research in Emerging Infectious Diseases (CREID)

The global network involves multidisciplinary investigations into how and where viruses and other pathogens can emerge from wildlife and spillover to cause disease in people. Research is led by 10 Centers and one Coordinating Center and will involve collaborations with peer institutions in the United States and 28 other countries.

Read more about this network: CREID Network

Main Areas of Focus

Research projects will include surveillance studies to identify previously unknown viral causes of febrile illnesses in humans, the animal sources of viral or other disease-causing pathogens, and to determine what genetic or other changes make these pathogens capable of infecting humans. Other research by the CREID investigators will involve developing reagents and diagnostic assays to improve detection of emerging pathogens as well as studies aimed at detailing human immune responses to new or emerging infectious agents. Overall, the breadth of research projects to be carried out in the CREID network will allow for study of disease spillover in multiple phases of the process: where pathogens first emerge from an animal host; at the borders between wild and more populated areas, where and when rapid human-to-human transmission occurs; and, finally, how transmission is facilitated in urban areas, where epidemic spread can occur.

Locations

Primary awardees for the CREID network and regions of focus include: 

  • Donald Brambilla, Ph.D., RTI International, Research Triangle Park, North Carolina
  • Tony Moody, M.D., Duke University School of Medicine, Durham, North Carolina
    CREID Coordinating Center
  • Kristian Andersen, Ph.D., Scripps Research, La Jolla, California
    West African Emerging Infectious Disease Research Center
    West Africa
  • Eva Harris, Ph.D., University of California, Berkeley
    American and Asian Centers for Arboviral Research and Enhanced Surveillance (A2CARES)
    Central and South America, South Asia
  • Christine Johnson, VMD, Ph.D., University of California, Davis, School of Veterinary Medicine
    Epicenter for Emerging Infectious Disease Intelligence
    Central Africa and South America
  • M. Kariuki Njenga, Ph.D., Washington State University, Pullman
    Center for Research in Emerging Infectious Diseases-East and Central Africa
    East and Central Africa
  • Anavaj Sakuntabhai, Ph.D., Institut Pasteur, Paris, France 
    West Africa and Southeast Asia
  • Nikos Vasilakis, Ph.D., University of Texas Medical Branch, Galveston
    Central and South America
  • Wesley C. Van Voorhis, M.D., Ph.D., University of Washington, Seattle
    South America, West and South Africa, Middle East, and Asia
  • David Wang, Ph.D., Washington University School of Medicine, St. Louis, Missouri 
    Asia, East Africa
  • Scott C. Weaver, Ph.D., University of Texas Medical Branch, Galveston
    West Africa

Contact Information

News and Announcements

Nov. 17, 2021: NIAID Supports Early-Career Researchers in Emerging Infectious Diseases

Aug. 27, 2020: NIAID Establishes Centers for Research in Emerging Infectious Diseases

Content Coordinator
Stephanie Coomes
Cynthia Rojas
Content Manager
Mason Booth

Virology—Integrated Research Facility at Fort Detrick

The virology team focuses on gaining a deeper understanding of viral pathogenesis and advancing clinical approaches to assist in managing diseases. The team works with a range of high-consequence viral pathogens.

The team leverages fundamental methodologies, such as: 

Subscribe to