Emerging Infections Research to Improve Global Health
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Our Work:
The Duke Human Vaccine Institute leads the field with cutting edge vaccine research against infectious diseases that impact global health. We conduct basic and translational research to develop novel vaccines, therapeutics and diagnostics for diseases such as HIV-1, influenza, tuberculosis, malaria, ebola, cytomegalovirus and zika flavivirus. Several of our basic science discoveries are currently being produced in Good Manufacturing Practice (CGMP) facilities for early phase vaccine trials.
Our Mission:
To
develop vaccines and therapeutics against diseases of global importance while training the next generation of scientists.
Our Values:
Collaboration, Excellence and Innovation
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Our Members: 18
Primary Investigators |
207
Staff Members
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Follow us on social media!
www.dhvi.duke.edu
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Message from the Director
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2019 has been a productive and rewarding year for the Duke Human Vaccine Institute. As we continue to grow as an Institute, it is important to reflect on our achievements, portfolios and discoveries as we move into the new year.
The DHVI received a $129 million NIAID grant to complete our HIV vaccine work. We also received a contract from NIAID for a universal flu vaccine that could be worth $400 million over the next few years. It is truly an honor for DHVI to have the opportunity to contribute to society by working on these two important vaccines. Both of these awards, and many other awards to faculty and staff, signify the hard work and accomplishments of all this year in DHVI.
Please enjoy this brief review of highlighted achievements, programs and ongoing studies from 2019.
Bart Haynes, M.D.
Director, DHVI
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Staff & Research
Genevieve Fouda
Eleanor Semmes
Amanda Lucifer
The Duke Vaccine Trial Unit
DHVI Accessioning Unit
Richard Scearce
2019 Outstanding Leadership in Scientific Training Award
Maria Blasi
Wilton Williams
Hilary Bouton-Verville
Daniel Tonkin
Patti Hanline
Tom Yee
Kent Stone
2019 Highly Cited Researchers
Munir Alam
Mattia Bonsignori
Guido Ferrari
Barton Haynes
David Montefiori
Tony Moody
Georgia Tomaras
Robert Parks
Norman P. Salzman Memorial Plenary Lecture, NIH
Barton Haynes
2019 SOM Duke Management Academy
Nicole Yates
Fall 2019 Duke Incubation Fund
Mattia Bonsignori
Sallie Permar
Tulika Singh
Christine Daniels
Stephanie Langel
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The NIAID funded Consortia for HIV/AIDS Vaccine Development (CHAVD) was awarded to the Duke Human Vaccine Institute to undertake the immunologic research that will tackle the major scientific obstacles in the development of an effective HIV-1 vaccine. The Duke CHAVD, led by
Barton Haynes, M.D
.
,
will build on the progress that was made by the previous CHAVI and
CHAVI-ID
consortium. The Duke CHAVD will coordinate a multidisciplinary team of researchers focused on iterative approaches to accelerate HIV vaccine development by addressing key immunogen design roadblocks to the discovery and development of a safe and effective antibody-mediated preventive HIV vaccine candidate.
Read press release
here
.
The Duke Collaborative Influenza Vaccine Innovation Centers (CIVICs)
is an NIH sponsored multi-contract awarded to the Duke Human Vaccine Institute in an effort to develop a longer-lasting, more broadly protective vaccine to replace seasonal flu shots. CIVICs is made up of three components: Vaccine Center (Component A), led by
Tony Moody, M.D.
,
will focus on basic immunology and virology research to identify potential influenza vaccine candidates; Manufacturing and Toxicology Core (Component B), led by
Matthew Johnson, Ph.D
.
,
will develop and manufacture cGMP candidate influenza vaccines for Phase I clinical trials with vaccine candidates coming from the Duke Vaccine Center, as well as other vaccine centers; and the Clinical Trials Core (Component C), led by
Chip Walter, M.D., M.P.H
,
will test the vaccine candidates designed by Component A and produced by Component B in clinical trials.
Read press release
here
.
The NIAID/NIH funded contract,
Virology Quality Assurance Program (VQA)
,
was awarded to
Thomas Denny, MSc, M.Phil
,
to
provide quality assurance and proficiency testing for virologic-based assays primarily for HIV, and other viral pathogens. The VQA program will promote effective assay procedures and increase data integrity within clinical studies. Additionally, the program will work to ensure the validity and comparability of data obtained across sites by providing laboratories with proficiency testing and assay run controls.
Read press release
here
.
The Duke Regional Biocontainment Laboratory (RBL)
, led by
Greg Sempowski, Ph.D, joined a multi-disciplinary team on a 10 year contract, entitled “Development and Utilization of a Monoclonal Antibody Platform Prototype for Development of Monoclonal Antibodies as Medical Countermeasures Against Threats of Interest.” This contract was awarded to Ology Bioservices, Inc, by the Platforms for Rapid Integrated Solutions for Medical Countermeasures (PRISM) office within the US Department of Defense. The program will target Plague and will focus on producing high quality monoclonal antibodies that will protect individuals who may be exposed to this deadly agent. DHVI faculty member
Dr. Mattia Bonsignori will also be involved in this effort.
Read press release
here
.
Sallie Permar, M.D., Ph.D.
,
received an NIAID P01 on congenital CMV, entitled,"Immunologic and Virologic Determinants of Congenital Cytomegalovirus Transmission and Disease in Rhesus Monkeys". This five year program will bring together the three national primate centers (University of California, Davis, Tulane, and Oregon Health Sciences University), with Duke as the central hub. The program will work to establish what vaccine targets are most critical for protection against congenital CMV transmission and disease and end the stalemate in congenital CMV vaccine research by defining the key immune responses and viral-host interactions that dictate primary fetal CMV transmission and disease. Read announcement
here
.
Munir Alam, Ph.D.
received a HIVRAD P01, titled, "Immunogen Design for Induction of HIV distal gp41 broadly neutralizing antibodies" to design immunogens that can initiate and induce neutralizing antibodies targeting the HIV-1 Envelope membrane proximal external region (MPER). Dr. Munir and team will work in collaboration with Scripps Institute and Harvard University to combine structure and lineage based vaccine development strategies to design immunogens that will initiate and select potent distal MPER broadly neutralizing antibodies (bnAb) B cell lineages that are not polyreactive and therefore easier to induce. Together their expertise will be a powerful approach to the problem of vaccine induction of disfavored antibody lineages in general and distal MPER bnAbs in particular. Read announcement
here
.
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DHVI Mentoring & Training Program (DTMP)
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The DHVI Training and Mentoring Program
trains and mentors undergraduates, graduates, and post-graduate research fellows who work in concert with Duke faculty and staff. The program, led by Co-Directors, Drs.
Maria Blasi
and
Wilton Williams
, provides trainees a collaborative research environment to academically support and train the next generation of socially conscious, superb research scientists who are dedicated to solving societal problems.
The DTMP aims to expand each trainee's knowledge base through mentoring, research seminars & lectures, journal clubs, research ethics workshops, scientific writing and presentation workshops, independent research presentations and collaborative research.
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The DTMP currently includes
13 postdoctoral researchers,
14 graduates, and
7 undergraduates.
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DTMP Research Areas
Antibody Discovery, Bacteriology, Bioformatics & Data Science, Clinical Trials, Diagnostics & Biomarkers, Genetic, Genomics & Gene Regulation, Immune Monitory, Immunology, Infectious Diseases, Microbiome, Mother to Child Transmission, Protein Engineering, Structural Biology, Quality Oversight, Vaccine Development and Virology
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2019 Meeting & Conference Highlights
Postdoctoral Associate
Dr. Ashley Nelson
received an Early Investigator Travel award to present her work on a vaccine regimen to reduce the risk of HIV transmission from mother-to-child at the 37th Annual Symposium on Nonhuman Primate Models for AIDS.
Postdoctoral Associate
Dr. Ria Goswami
was awarded the New Investigator Scholarship to present her work on HIV viral load and antibody responses at the 2019 Conference on Retroviruses & Opportunistic Infections.
PhD Candidate
Lindsay Dahora
presented her work on typhoid fever immune correlates at the 2019 Next Generation Rotavirus Vaccine Developer's Meeting.
Postdoctoral Associate
Dr. Marina Tuyishime
presented her work on eliminating HIV-1 infected cells by ADCC-mediating monoclonal antibodies at the HIV Vaccine Trials Network (HVTN) full group meeting and the 9th International Workshop on HIV Persistence during Therapy.
Senior Research Associate
Dr. Yi-Yi Lin
won the poster prize at the 2019 Miami Winter Symposium: Evolving Concepts in HIV and Emerging Viral Infections, for his poster entitled, "Persistence of Antigen Expression is Associate with Long-Term Immunity Induced by Integrase-Defective Lentiviral Vector (IDLV)".
MD-PhD candidate,
Jennifer Jenks
presented her work on immune responses against CMV acquisition at the International Herpesvirus Workshop, IDSA IDweek Conference, the International CMV Workshop and the Keystone Symposia.
Postdoctoral Associate
Dr. Stephanie Langel
was one of three winners of the postdoctoral poster competition at the Duke Department of Molecular Genetics and Microbiology's annual retreat.
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2019 Grants & Scholarships
Postdoctoral Associate
Dr. Ashley Nelson
received the
Duke Clinical Translational Science Award Postdoctoral TL1
for her project, "Determinants of neutralizing antibody breadth in HIV-infected children".
Postdoctoral Associate
Dr. Ria Goswami
received the
Children's Miracle Network Hospital Research Award
for her project, "Identification of immune pathways involved in reducing the HIV reservoir in pediatric tonsillar cells via a novel Hsp90-inhibitor treatment".
MD-PhD candidate
Jennifer Jenks
received three awards this year: The
2020 Infectious Disease Society of America G.E.R.M
for her project, "Immune correlates of protection against congenital cytomegalovirus transmission in HIV+ mother/infant cohort", the
CMV Scholars Research Award
for her project, "Humoral immune correlates for cytomegalovirus gb/MF59 vaccine against viral acquisition" and the
International CMV Workshop Trainee Award
for project, "Vaccine-Elicited Antibody Responses Differ in Two Historical Cytomegalovirus gB/MF59 Vaccine Cohorts".
PhD candidate and visiting graduate student
Caesar Lopez Angel
received the
NIH HVTN Research and Mentoring Program Scholar
for his project, "Defining the role of immune heterogeneity and preexisting CMV immunity in protective HIV-1 vaccination".
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Learn about DTMP Co-Director Maria Blasi, Ph.D. in our Staff Spotlight
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Dr. Maria Blasi is an Assistant Professor in the Department of Medicine, Division of Infectious Diseases at Duke University Medical Center and Co-Director of the Duke Human Vaccine Institute Mentoring and Training Program (DTMP).
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K.O. Saunders, B.F. Haynes
et al., Targeted selection of HIV-specific antibody mutations by engineering B cell maturation.
Science 366(6470) (2019).
doi:10.1126/science.aay7199
M. Blasi, M. Klotman
et al.
,
Detection of Donor's HIV Strain in HIV-Positive Kidney Transplant Recipient.
New England Journal of Medicine,
in Press (2019)
C.C. Labranch, D.C. Montefiori
et al
., Neutralization-guided design of HIV-1 envelope trimers with high affinity for the unmutated common ancestor of CH235 lineage CD4bs broadly neutralizing antibodies.
PLos Pathog 15(9)
(2019)
,
doi: 10.1371/journal.ppat.1008026
F. Veglia, D.I. Gabrilovich
et al
.,
Fatty acid transporter 2 reprograms neutrophils in cancer.
Nature 569
,
73–78 (2019).
doi: 10.1038/s41586-019-1118-2
D.R. Martinez, S.R. Permar
et al
.,
Fc Characteristics Mediate Selective Placental Transfer of IgG in HIV-Infected Women.
Cell 178
, 190-201(2019)
doi: 10.1016/j.cell.2019.05.046.
R. Goswami, S.R. Permar
et al
.,
Analytical Treatment Interruption after Short-Term Antiretroviral Therapy in a Postnatally Simian-Human Immunodeficiency Virus-Infected Infant Rhesus Macaque Model.
MBio 10
(2019)
doi: 10.1128/mBio.01971-19.
L.P. Hale, G.D. Sempowksi
et al
.,
Late effects of total body irradiation on hematopoietic recovery and immune function in rhesus macaques
.
PLoS One
14
(2019)
e0210663.
doi: 10.1371/journal.pone.0210663
T.C. Bradley, B.F. Haynes
et al
.
, RAB11FIP5 Expression and Altered Natural Killer Cell Function Are Associated with Induction of HIV Broadly Neutralizing Antibody Responses.
Cell 175(2)
, 387-399 (2019).
doi: 10.1016/j.cell.2018.08.064
S. Neidich, G.D. Tomaras
et al
.,
Antibody Fc effector functions and IgG3 associate with decreased HIV-1 risk.
J Clin Invest
129(11)
, 4838-4849 (2019).
doi.org/10.1172/JCI126391
L. Dahora, G.D. Tomaras
et al
.,
IgA and IgG1 Specific to Vi Polysaccharide of
Salmonella
Typhi Correlate With Protection Status in a Typhoid Fever Controlled Human Infection Model.
Front. Immunol. 10
,
doi.org/10.3389/fimmu.2019.02582
I.D. Shterev, G.D. Sempowski
et al
.,
Bayesian Multi-Plate High-Throughput Screening of Compounds.
Sci Rep 8
, 9551 (2018).
doi: 10.1038/s41598-018-27531
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R. Henderson, S.M. Alam
et al
.,
Selection of immunoglobulin elbow region mutations impacts interdomain conformational flexibility in HIV-1 broadly neutralizing antibodies.
Nat Commun 10 (1)
, 654 (2019)
doi:10.1038/s41467-019-08415-7
E.G. Wee, T. Hanke
et al
.,
Parallel Induction of CH505 B Cell Ontogeny-Guided Neutralizing Antibodies and tHIVconsvX Conserved Mosaic-Specific T Cells against HIV-1.
Mol Ther Methods Clin Dev. 14
,
148-160 (2019).
doi: 10.1016/j.omtm.2019.06.003
J.R. Francica, R.A. Seder
et al
., Star nanoparticles delivering HIV-1 peptide minimal immunogens elicit near-native envelope antibody responses in nonhuman primates.
PLoS Biol 17(6)
(2019)
.
doi: 10.1371/journal.pbio.3000328
C.W. Woods, E.B. Walter
et al
.,
An observer blinded, randomized, placebo-controlled, phase I dose escalation trial to evaluate the safety and immunogenicity of an inactivated West Nile virus Vaccine, HydroVax-001, in healthy adults
.
Vaccine 37,
4222-4230 (2019).
doi: 10.1016/j.vaccine.2018.12.026
K. Wagh, B. Korber
et al
.
, Completeness of HIV-1 Envelope Glycan Shield at Transmission Determines Neutralization Breadth.
Cell Rep 25(4)
, 893-908 (2019).
doi: 10.1016/j.celrep.2018.09.087
T. Hayashi, K. Nakachi
et al
.
, Impact of early life exposure to ionizing radiation on influenza
K. Wiehe, B.F. Haynes
et al
.,
Functional Relevance of Improbable Antibody Mutations for HIV Broadly Neutralizing Antibody Development.
Cell Host Microbe 23(6)
, 759-765 (2019)
doi: 10.1016/j.chom.2018.04.018
T. Nyanhete, G.D. Tomaras
et al
.,
HLA class II-Restricted CD8+ T cells in HIV-1 Virus Controllers.
Sci Rep 9
,
10165 (2019)
doi:10.1038/s41598-019-46462-8
N. Pardi, D. Weissman
et al
.,
Nucleoside-modified mRNA vaccines induce potent T follicular helper and germinal center B cell responses.
J Exp Med 15(6)
, 1571-1588 (2018).
doi: 10.1084/jem.20171450
M. Bonsignori, B.F. Haynes
et al
.,
Inference of the VRC01 Antibody Lineage Unmutated Common Ancestor Reveals Alternative Pathways to Overcome a Key Glycan Barrier
.
Immunity
49
,
1162-1174 (2018).
doi:10.1016/j.immuni.2018.10.015
Click
here
for a comprehensive list of all DHVI publications.
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New Affiliate Faculty Members
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Assistant Professor of Pharmacology and Cancer Biology
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Assistant Professor of Molecular Genetics and Microbiology
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Assistant Professor of Molecular Genetics and Microbiology
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Good Manufacturing Facility
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The DHVI Good Manufacturing Practices Facility consists of five manufacturing suites featuring state of-the-art single-use equipment for the manufacture of HIV antigens, mRNA therapies and vaccines, and other cell or bacterial-based products as required. The manufacturing capability is complimented by dedicated teams for cell line development, process development, analytical development and quality control, program management, quality assurance and regulatory teams. The facility is led by
Dr. Matthew Johnson
and managed under a quality system to ensure that that all cGMP requirements are met for the manufacture and release of clinical products.
Current Products:
EnvSeq-1 (CH505 TF, w53, w78 and w100 gp120s)
Manufacturer: KBI
CH505 M5 gp120
Manufacturer: DHVI
A244d11 gp120
Manufacturer: DHVI
Clinical Trial: RV564 (pending), RV509 (pending)
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Having a
Current Good Manufacturing Practices (cGMP) facility
as part of the DHVI makes us one of the most globally advanced vaccine Institutes in the country. It positions the DHVI teams to speed translational efforts moving research discoveries to impactful clinical trials, while having an infrastructure to respond to emerging public health threats.
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HVTN 115:
A study to evaluate the safety and immunogenicity of EnvSeq-1 Envs adjuvanted with GLA-SE, administered alone or with DNA Mosaic-Tre env, in healthy, HIV-uninfected adult participants. Read more
here
.
HVTN 121: A clinical
trial being performed at Duke and at the University of Alabama at Birmingham that is examining the safety of the alum-adjuvanted vaccine AIDSVAX B/E in participants who have systemic lupus erythematosus (SLE). Read more
here
.
HVTN 123
: A study to compare the safety and immunogenicity of CH505TF gp120 produced from stably transfected cells to CH505TF gp120 produced from transiently transfected cells in healthy, HIV-1 uninfected adult participants
HVTN 133:
A clinical trial to evaluate the safety and immunogenicity of an HIV-1 MPER peptide liposome vaccine in healthy, HIV-uninfected adult participants
HVTN 135:
A clinical trial to evaluate the safety and immunogenicity of the HIV-1 CH505 transmitted/founder (TF) gp120 adjuvanted with GLA-SE in healthy, HIV-exposed infants
HVTN 106: A study to
evaluate the safety and immune response to three DNA vaccines and a MVA-CMDR vaccine that may boost the immune response to the DNA vaccines in healthy, HIV-uninfected adults. Read more
here
.
Clinical Trials managed by the Duke Vaccine and Trials Unit (DTVU)
The
Duke Vaccine and Trials Unit
is a consortium of investigators committed to conducting clinical investigations related to the control and prevention of infectious disease with an overarching goal of furthering our understanding of vaccine immune responses, correlates of protection from infection and enhancing vaccine safety.
CISA Apnea
: A multi-center study to assess apnea following vaccination in premature infants receiving their standard of care two-month vaccinations. Read more
here.
14-1053
: An observational study to assess the prevalence and outcomes of primary pulmonary coccidioidomycosis (also referred to as Valley Fever (VF) Pneumonia or acute onset valley fever) in persons presenting with community acquired pneumonia. Recruitment will take place at sites in areas where VF is endemic, including Arizona and California. Read more
here
.
CISA Flublok
: A study to evaluate the safety of Flublok®, the first recombinant inactivated influenza vaccine (RIV), and Flulaval, quadrivalent-inactivated influenza vaccine (IIV4), in pregnant women. This study will also evaluate adverse outcomes in infants, local and systemic reactogenicity, vaccine-related adverse events and immunogenicity following maternal RIV. Read more
here
.
16-0058
: A study to assess the plasma and intrapulmonary pharmacokinetics of Fosfomycin (6 g), delivered intravenously over three doses, following a bronchoscopy. Duke will enroll 30 subjects for this study.
18-0011
: A Duke specific site study to assess the sfaety, reactogenicity, and immunogenicity of two Quadrivalent seasonal Influenza vaccines (Flublok or Fluzone) with or without one of two adjuvants (AF03 or Advax-CpG55.2).
18-0010
: A natural history study of controlled influenza infection to assess the effect of pre-existing immunity on clinical and immunological responses. Subjects’ clinical manifestations, viral shedding and immunological responses will be characterized.
Click
here
for more information and additional DVTU studies.
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