Mattia Bonsignori, M.D., M.S.

Education:

M.D., M.S., University of Insubria Medical School, Varese, Italy

Mattia Bonsignori, M.D., M.S.

Kathryn Foulds, Ph.D.

Contact: fouldsk@mail.nih.gov

Education:

Ph.D., 2003, University of Pennsylvania

M.S., 1998, Johns Hopkins University

Photo of Kathryn Foulds, Ph.D.

Ursula Buchholz, Ph.D.

Education:

Ph.D., 1994, Free University of Berlin, Germany

Ursula Buchholz, Ph.D.

Adrian McDermott, M.Sc., Ph.D.

Adrian McDermott, M.Sc., Ph.D.

Richard Herbert, D.V.M.

Education:

D.V.M., 1993, Virginia-Maryland Regional College of Veterinary Medicine, College Park, MD

A Potential Role for Ibuprofen in Older Adults’ Immunity to RSV

Study Predicts Which Kids Hospitalized with RSV Likely to Worsen

Trio of COVID-Related Opportunities Cover Variety of Research Priorities

Funding News Editions:
See more articles in this edition

NIAID is participating in three notices of special interest (NOSIs) related to COVID-19, each focused on a distinct research topic:

  • Pathobiological mechanisms of post-acute sequelae of SARS-CoV-2 infection
  • Pediatric COVID-19 and respiratory viral co-infection
  • Vaccine hesitancy, uptake, and implementation among populations that experience health disparities

The three NOSIs leverage different funding opportunity announcements (FOAs), so take time to understand the requirements of each initiative to which you may apply.

Administrative Supplements To Study Post-Acute Sequelae

Through Notice of Special Interest (NOSI)—Availability of Administrative Supplements for Research on Pathobiological Mechanisms of Post-Acute Sequelae of SARS-CoV-2 Infection, current grantees may submit administrative supplement applications to support research on post-acute sequelae of SARS-CoV-2 infection (PASC).

The NOSI specifically calls for research to inform the diagnosis, prevention, mitigation, or treatment of PASC by elucidating the pathogenesis of post-acute sequelae and identify associated mechanistic pathways. Possible studies include:

  • Characterizing immune responses to better understand how autoantibodies develop
  • Studying host and environmental factors and associated biological pathways that mediate the intensity and duration of the neurological, metabolic, immunologic, hematologic, and cardiopulmonary and vascular dimensions of PASC
  • Conducting animal model studies of PASC pathobiology to evaluate intermediate or analogous endpoints of potential clinical correlates of PASC

The NOSI provides a much longer list of example topics, so be sure to read the research objectives section in full.

Keep in mind, administrative supplements require that the supported research be within the approved scope of an ongoing award. As our article “Understand Scope and Why It Matters for Managing Your Grant” implies, if studying the pathobiological mechanisms of post-acute sequelae is beyond the aims, objectives, and purposes of your current grant, then you should apply for a competitive revision rather than an administrative supplement. Before applying, we strongly encourage you to discuss with the program officer assigned to your ongoing award whether your proposed supplement is within scope.

Act quickly! Applications are due on January 24, 2022.

To apply, use the FOA Administrative Supplements to Existing NIH Grants and Cooperative Agreements (Parent Admin Supp, Clinical Trial Optional). List “NOT-OD-22-038” in the Agency Routing Identifier field (box 4B) of the SF 424 (R&R) Form. 

Your application budget should not exceed $750,000 in direct costs. The NOSI strongly encourages applicants to propose a one-year project period.

Read Frequently Asked Questions for Notice of Special Interest (NOSI): Availability of Administrative Supplements for Research on Pathobiological Mechanisms of Post-Acute Sequelae of SARS-CoV-2 Infection (PASC) for additional instructions and eligibility requirements.

R01, R21 Awards for Pediatric COVID-19 and Respiratory Co-Infection Research

Propose new research projects on the impact of co-infection with COVID-19 and other viruses in children as well as whether co-infections increase vulnerability to SARS-CoV-2 disease through Notice of Special Interest (NOSI)—Pediatric COVID-19 and Respiratory Viral Co-Infection.

Examples of relevant research questions include:

  • Does past or concurrent SARS-CoV-2 infection impact susceptibility to and increased severity from infections caused by respiratory syncytial virus (RSV) and other viruses in children?
  • Does co-infection with RSV and other respiratory viruses increase severity of SARS CoV-2 in the lower respiratory tract in children?
  • How does COVID-19 vaccination in children impact the epidemiology of co-infections?

The NOSI lists many additional topics of interest.

Apply through either of the following FOAs:

List “NOT-HL-22-004” (without quotation marks) in the Agency Routing Identifier field (box 4B) of the SF 424 (R&R) Form. 

Refer to the FOA through which you apply for administrative requirements around budget, project period, eligibility, and submission deadlines.

The NOSI will remain active through September 8, 2025.

R01 Awards for Vaccine Hesitancy, Uptake, and Implementation Research

The Notice of Special Interest (NOSI)—Research To Address Vaccine Hesitancy, Uptake, and Implementation Among Populations That Experience Health Disparities encourages research projects to identify the most effective interventions and strategies to increase the reach, access, acceptance, and vaccine completion among populations that experience health disparities.

Successful grantees will assess:

  • Community-engaged interventions to facilitate vaccination uptake in clinical and community contexts
  • Organizational, local, state, and federal policies and initiatives that mitigate or exacerbate disparities in vaccine access, uptake, and series completion
  • Barriers to increasing reach, access, and uptake of vaccinations among populations who experience health disparities

The NOSI differentiates between primary data collection studies and secondary data analysis studies. If your application includes primary data collection, you must partner with a key community stakeholder (as defined in the NOSI). If your study will introduce an intervention, reference NIH’s Research Methods Resources while designing your research plan.  

To ensure data harmonization, investigators should leverage PhenX Toolkit and Disaster Research Response (DR2) Program resources when constructing surveys and protocols.

Whether your proposed research project meets NIH’s definition of a clinical trial will determine the FOA through which you should apply:

List “NOT-MD-22-006” (without quotation marks) in the Agency Routing Identifier field (box 4B) of the SF 424 (R&R) Form. 

Refer to the FOA through which you apply for administrative requirements around budget, project period, eligibility, and submission deadlines.

The NOSI will remain active through January 8, 2023.

Contact Us

Email us at deaweb@niaid.nih.gov for help navigating NIAID’s grant and contract policies and procedures.

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Mattia Bonsignori, M.D., M.S.

Chief, Translational Immunobiology Unit
Contact Information
Mattia Bonsignori, M.D., M.S.
Mattia Bonsignori, M.D., M.S.
Mattia Bonsignori, M.D., M.S.
Credit
NIAID

Major Areas of Research

  • Genetic and functional antibody evolution
  • Effect of pre-existing immunity and autoreactivity on the maturation and function of B cell responses after infection and upon vaccination
  • Immunogen selection, design, and vaccine development
  • Antibody-based prophylactic and therapeutic countermeasures
  • Immuno-monitoring
  • Development of high-throughput assays
  • Pathogens: HIV-1, flaviviruses, influenza virus, herpesviruses, betacoronaviruses, emerging pathogens

Program Description

Humoral immunity is an essential component to clear infections and robust, long-lasting B cell-mediated memory is a correlate of protection for many vaccines. However, numerous factors related to both host and pathogen can influence the quality of humoral memory upon infection and vaccination. Studying the origin, maturation and evolutionary barriers of functionally active B cell clones provides valuable information on the natural history of effective and abherrant B cell reponses and a platform for the rational selection of immunogen designs.

The mission of the Translational Immunobiology Unit is to extend the basic understanding of B cell selection, clonal expansion and maturation into memory responses; to gather information from the natural evolution of B cell responses to inform effective immunogen designs, and to identify prophylactic and therapeutic antibody-based countermeasures. Studies will encompass primarily human and non-human primate specimens, as well as murine models, and will use multiple virus models, including HIV, flaviviruses, influenza virus, herpesviruses and betacoronaviruses.

Biography

Dr. Bonsignori received his M.D. and M.S. in clinical microbiology and virology from the University of Insubria Medical School in Varese, Italy. He conducted postdoctoral research in the Department of Immunology at St. Jude Children’s Research Hospital in Memphis, Tennessee before being appointed research associate at the Duke Human Vaccine Institute, Duke University School of Medicine in Durham, North Carolina, where his activity focused primarily on HIV vaccine development. In 2009, he established the Laboratory of B-cell Repertoire Analysis and ultimately attained the position of associate professor of medicine. In the HIV field, Dr. Bonsignori isolated multiple broadly neutralizing antibody B cell lineages from chronically HIV-1 infected individuals and characterized antibody/virus co-evolution to rationally select immunogen candidates for sequential vaccination schemes. Dr. Bonsignori developed a high-throughput memory B cell culture system for the functional screening of memory B cells at the single-cell level and conceptualized a novel framework for steering the immune response through immunogen design based on the probability of individual mutations and their effect on antibody effector functions. He later applied some of the technologies and workflows to study B cell responses to P. falciparum and Zika virus. Before NIAID, Dr. Bonsignori supported the Duke University student COVID-19 surveillance program by establishing a high-throughput workflow for the rapid accessioning, pooling and storage of nasal swab samples that sustained the screening of up to 20,000 samples per week.  Dr. Bonsignori joined the Laboratory of Infectious Diseases in March 2021.

Selected Publications

SM, Zhang R, Montefiori DC, Henderson R, Nie X, Kelsoe G, Moody MA, Chen X, Joyce MG, Kwong PD, Connors M, Mascola JR, McGuire AT, Stamatatos L, Medina-Ramírez M, Sanders RW, Saunders KO, Kepler TB, Haynes BF. Inference of the HIV-1 VRC01 Antibody Lineage Unmutated Common Ancestor Reveals Alternative Pathways to Overcome a Key Glycan Barrier. Immunity. 2018 Dec;49(6):1162-1174.e8.

Bonsignori M, Kreider EF, Fera D, Meyerhoff RR, Bradley T, Wiehe K, Alam SM, Aussedat B, Walkowicz WE, Hwang KK, Saunders KO, Zhang R, Gladden MA, Monroe A, Kumar A, Xia SM, Cooper M, Louder MK, McKee K, Bailer RT, Pier BW, Jette CA, Kelsoe G, Williams WB, Morris L, Kappes J, Wagh K, Kamanga G, Cohen MS, Hraber PT, Montefiori DC, Trama A, Liao HX, Kepler TB, Moody MA, Gao F, Danishefsky SJ, Mascola JR, Shaw GM, Hahn BH, Harrison SC, Korber BT, Haynes BF. Staged induction of HIV-1 glycan-dependent broadly neutralizing antibodies. Sci Transl Med. 2017 Mar;9(381):eaai7514.

Bonsignori M, Zhou T, Sheng Z, Chen L, Gao F, Joyce MG, Ozorowski G, Chuang GY, Schramm CA, Wiehe K, Alam SM, Bradley T, Gladden MA, Hwang KK, Iyengar S, Kumar A, Lu X, Luo K, Mangiapani MC, Parks RJ, Song H, Acharya P, Bailer RT, Cao A, Druz A, Georgiev IS, Kwon YD, Louder MK, Zhang B, Zheng A, Hill BJ, Kong R, Soto C; NISC Comparative Sequencing Program, Mullikin JC, Douek DC, Montefiori DC, Moody MA, Shaw GM, Hahn BH, Kelsoe G, Hraber PT, Korber BT, Boyd SD, Fire AZ, Kepler TB, Shapiro L, Ward AB, Mascola JR, Liao HX, Kwong PD, Haynes BF. Maturation Pathway from Germline to Broad HIV-1 Neutralizer of a CD4-Mimic Antibody. Cell. 2016 Apr;165(2):449-63.

Gao F, Bonsignori M, Liao HX, Kumar A, Xia SM, Lu X, Cai F, Hwang KK, Song H, Zhou T, Lynch RM, Alam SM, Moody MA, Ferrari G, Berrong M, Kelsoe G, Shaw GM, Hahn BH, Montefiori DC, Kamanga G, Cohen MS, Hraber P, Kwong PD, Korber BT, Mascola JR, Kepler TB, Haynes BF. Cooperation of B cell lineages in induction of HIV-1-broadly neutralizing antibodies. Cell. 2014 Jul;158(3):481-91.

Bonsignori M, Wiehe K, Grimm SK, Lynch R, Yang G, Kozink DM, Perrin F, Cooper AJ, Hwang KK, Chen X, Liu M, McKee K, Parks RJ, Eudailey J, Wang M, Clowse M, Criscione-Schreiber LG, Moody MA, Ackerman ME, Boyd SD, Gao F, Kelsoe G, Verkoczy L, Tomaras GD, Liao HX, Kepler TB, Montefiori DC, Mascola JR, Haynes BF. An autoreactive antibody from an SLE/HIV-1 individual broadly neutralizes HIV-1. J Clin Invest. 2014 Apr;124(4):1835-43.

Bonsignori M, Hwang KK, Chen X, Tsao CY, Morris L, Gray E, Marshall DJ, Crump JA, Kapiga SH, Sam NE, Sinangil F, Pancera M, Yongping Y, Zhang B, Zhu J, Kwong PD, O'Dell S, Mascola JR, Wu L, Nabel GJ, Phogat S, Seaman MS, Whitesides JF, Moody MA, Kelsoe G, Yang X, Sodroski J, Shaw GM, Montefiori DC, Kepler TB, Tomaras GD, Alam SM, Liao HX, Haynes BF. Analysis of a clonal lineage of HIV-1 envelope V2/V3 conformational epitope-specific broadly neutralizing antibodies and their inferred unmutated common ancestors. J Virol. 2011 Oct;85(19):9998-10009.

Visit PubMed for a complete publication listing.

Section or Unit Name
Translational Immunobiology Unit
Lab/Program Name
Laboratory of Infectious Diseases
First Name
Mattia
Last Name
Bonsignori
Suffix
M.D., M.S.
Exclude from directory
Off
This Researcher/Clinician’s Person Page
Mattia Bonsignori, M.D., M.S.
Parent Lab/Program
Laboratory of Infectious Diseases
Program Description

Humoral immunity is an essential component to clear infections and robust, long-lasting B cell-mediated memory is a correlate of protection for many vaccines. However, numerous factors related to both host and pathogen can influence the quality of humoral memory upon infection and vaccination. Studying the origin, maturation, and evolutionary barriers of functionally active B cell clones provides valuable information on the natural history of effective and aberrant B cell responses and a platform for the rational selection of immunogen designs.

The mission of the Translational Immunobiology Unit is to extend the basic understanding of B cell selection, clonal expansion and maturation into memory responses; to gather information from the natural evolution of B cell responses to inform effective immunogen designs, and to identify prophylactic and therapeutic antibody-based countermeasures. Studies will encompass primarily human and non-human primate specimens, as well as murine models, and will use multiple virus models, including HIV, flaviviruses, influenza virus, herpesviruses and betacoronaviruses.

Selected Publications

SM, Zhang R, Montefiori DC, Henderson R, Nie X, Kelsoe G, Moody MA, Chen X, Joyce MG, Kwong PD, Connors M, Mascola JR, McGuire AT, Stamatatos L, Medina-Ramírez M, Sanders RW, Saunders KO, Kepler TB, Haynes BF. Inference of the HIV-1 VRC01 Antibody Lineage Unmutated Common Ancestor Reveals Alternative Pathways to Overcome a Key Glycan Barrier. Immunity. 2018 Dec;49(6):1162-1174.e8.

Bonsignori M, Kreider EF, Fera D, Meyerhoff RR, Bradley T, Wiehe K, Alam SM, Aussedat B, Walkowicz WE, Hwang KK, Saunders KO, Zhang R, Gladden MA, Monroe A, Kumar A, Xia SM, Cooper M, Louder MK, McKee K, Bailer RT, Pier BW, Jette CA, Kelsoe G, Williams WB, Morris L, Kappes J, Wagh K, Kamanga G, Cohen MS, Hraber PT, Montefiori DC, Trama A, Liao HX, Kepler TB, Moody MA, Gao F, Danishefsky SJ, Mascola JR, Shaw GM, Hahn BH, Harrison SC, Korber BT, Haynes BF. Staged induction of HIV-1 glycan-dependent broadly neutralizing antibodies. Sci Transl Med. 2017 Mar;9(381):eaai7514.

Bonsignori M, Zhou T, Sheng Z, Chen L, Gao F, Joyce MG, Ozorowski G, Chuang GY, Schramm CA, Wiehe K, Alam SM, Bradley T, Gladden MA, Hwang KK, Iyengar S, Kumar A, Lu X, Luo K, Mangiapani MC, Parks RJ, Song H, Acharya P, Bailer RT, Cao A, Druz A, Georgiev IS, Kwon YD, Louder MK, Zhang B, Zheng A, Hill BJ, Kong R, Soto C; NISC Comparative Sequencing Program, Mullikin JC, Douek DC, Montefiori DC, Moody MA, Shaw GM, Hahn BH, Kelsoe G, Hraber PT, Korber BT, Boyd SD, Fire AZ, Kepler TB, Shapiro L, Ward AB, Mascola JR, Liao HX, Kwong PD, Haynes BF. Maturation Pathway from Germline to Broad HIV-1 Neutralizer of a CD4-Mimic Antibody. Cell. 2016 Apr;165(2):449-63.

Gao F, Bonsignori M, Liao HX, Kumar A, Xia SM, Lu X, Cai F, Hwang KK, Song H, Zhou T, Lynch RM, Alam SM, Moody MA, Ferrari G, Berrong M, Kelsoe G, Shaw GM, Hahn BH, Montefiori DC, Kamanga G, Cohen MS, Hraber P, Kwong PD, Korber BT, Mascola JR, Kepler TB, Haynes BF. Cooperation of B cell lineages in induction of HIV-1-broadly neutralizing antibodies. Cell. 2014 Jul;158(3):481-91.

Bonsignori M, Wiehe K, Grimm SK, Lynch R, Yang G, Kozink DM, Perrin F, Cooper AJ, Hwang KK, Chen X, Liu M, McKee K, Parks RJ, Eudailey J, Wang M, Clowse M, Criscione-Schreiber LG, Moody MA, Ackerman ME, Boyd SD, Gao F, Kelsoe G, Verkoczy L, Tomaras GD, Liao HX, Kepler TB, Montefiori DC, Mascola JR, Haynes BF. An autoreactive antibody from an SLE/HIV-1 individual broadly neutralizes HIV-1. J Clin Invest. 2014 Apr;124(4):1835-43.

Bonsignori M, Hwang KK, Chen X, Tsao CY, Morris L, Gray E, Marshall DJ, Crump JA, Kapiga SH, Sam NE, Sinangil F, Pancera M, Yongping Y, Zhang B, Zhu J, Kwong PD, O'Dell S, Mascola JR, Wu L, Nabel GJ, Phogat S, Seaman MS, Whitesides JF, Moody MA, Kelsoe G, Yang X, Sodroski J, Shaw GM, Montefiori DC, Kepler TB, Tomaras GD, Alam SM, Liao HX, Haynes BF. Analysis of a clonal lineage of HIV-1 envelope V2/V3 conformational epitope-specific broadly neutralizing antibodies and their inferred unmutated common ancestors. J Virol. 2011 Oct;85(19):9998-10009.

Visit PubMed for a complete publication listing.

Major Areas of Research
  • Genetic and functional antibody evolution
  • Effect of pre-existing immunity and autoreactivity on the maturation and function of B cell responses after infection and upon vaccination
  • Immunogen selection, design, and vaccine development
  • Antibody-based prophylactic and therapeutic countermeasures
  • Immuno-monitoring
  • Development of high-throughput assays
  • Pathogens: HIV-1, flaviviruses, influenza virus, herpesviruses, betacoronaviruses, emerging pathogens

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
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