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Neonatal Rhesus Macaques Have Distinct Immune Cell Transcriptional Profiles following HIV Envelope Immunization.

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Date
2020-02
Authors
Han, Qifeng
Bradley, Todd
Williams, Wilton B
Cain, Derek W
Montefiori, David C
Saunders, Kevin O
Parks, Robert J
Edwards, Regina W
Ferrari, Guido
Mueller, Olaf
Shen, Xiaoying
Wiehe, Kevin J
Reed, Steven
Fox, Christopher B
Rountree, Wes
Vandergrift, Nathan A
Wang, Yunfei
Sutherland, Laura L
Santra, Sampa
Moody, M Anthony
Permar, Sallie R
Tomaras, Georgia D
Lewis, Mark G
Van Rompay, Koen KA
Haynes, Barton F
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(25 total)
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Abstract
HIV-1-infected infants develop broadly neutralizing antibodies (bnAbs) more rapidly than adults, suggesting differences in the neonatal versus adult responses to the HIV-1 envelope (Env). Here, trimeric forms of HIV-1 Env immunogens elicit increased gp120- and gp41-specific antibodies more rapidly in neonatal macaques than adult macaques. Transcriptome analyses of neonatal versus adult immune cells after Env vaccination reveal that neonatal macaques have higher levels of the apoptosis regulator BCL2 in T cells and lower levels of the immunosuppressive interleukin-10 (IL-10) receptor alpha (IL10RA) mRNA transcripts in T cells, B cells, natural killer (NK) cells, and monocytes. In addition, immunized neonatal macaques exhibit increased frequencies of activated blood T follicular helper-like (Tfh) cells compared to adults. Thus, neonatal macaques have transcriptome signatures of decreased immunosuppression and apoptosis compared with adult macaques, providing an immune landscape conducive to early-life immunization prior to sexual debut.
Type
Journal article
Subject
HIV-1 envelope
immunization
neonates
rhesus macaques
single-cell RNA sequencing
transcriptome
Permalink
https://hdl.handle.net/10161/20297
Published Version (Please cite this version)
10.1016/j.celrep.2019.12.091
Publication Info
Han, Qifeng; Bradley, Todd; Williams, Wilton B; Cain, Derek W; Montefiori, David C; Saunders, Kevin O; ... Haynes, Barton F (2020). Neonatal Rhesus Macaques Have Distinct Immune Cell Transcriptional Profiles following HIV Envelope Immunization. Cell reports, 30(5). pp. 1553-1569.e6. 10.1016/j.celrep.2019.12.091. Retrieved from https://hdl.handle.net/10161/20297.
This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.
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Scholars@Duke

Cain

Derek Wilson Cain

Associate Professor in Medicine
My research focuses on the interactions of T cells and B cells during infection or following vaccination. I am particularly interested in the inter- and intracellular events that take place within germinal centers, the anatomic site of antibody evolution during an immune response.
Ferrari

Guido Ferrari

Professor in Surgery
The activities of the Ferrari Laboratory are based on both independent basic research and immune monitoring studies. The research revolves around three main areas of interest: class I-mediated cytotoxic CD8+ T cell responses, antibody-dependent cellular cytotoxicity (ADCC), gene expression in NK and T cellular subsets upon infection with HIV-1. With continuous funding over the last 11 years from the NIH and Bill & Melinda Gates Foundation along with many other productive collaborations wi
Haynes

Barton Ford Haynes

Frederic M. Hanes Distinguished Professor of Medicine
The Haynes lab is studying host innate and adaptive immune responses to the human immunodeficiency virus (HIV), tuberculosis (TB), and influenza in order to find the enabling technology to make preventive vaccines against these three major infectious diseases. Mucosal Immune Responses in Acute HIV Infection The Haynes lab is working to determine why broadly neutralizing antibodies are rarely made in acute HIV infection (AHI), currently a major obstacle in the de
Montefiori

David Charles Montefiori

Professor in Surgery
Dr. Montefiori is Professor and Director of the Laboratory for AIDS Vaccine Research and Development in the Department of Surgery, Division of Surgical Sciences, Duke University Medical Center. His major research interests are viral immunology and AIDS vaccine development, with a special emphasis on neutralizing antibodies. One of his highest priorities is to identify immunogens that generate broadly cross-reactive neutralizing antibodies for inclusion in HIV vaccines.  Many aspects of the
Moody

Michael Anthony Moody

Professor of Pediatrics
Tony Moody, MD is a Professor in the Department of Pediatrics, Division of Infectious Diseases and Professor in the Department of Immunology at Duke University Medical Center. Research in the Moody lab is focused on understanding the B cell responses during infection, vaccination, and disease. The lab has become a resource for human phenotyping, flow characterization, staining and analysis at the Duke Human Vaccine Institute (DHVI). The Moody lab is currently funded to study influenza, syphil
Permar

Sallie Robey Permar

Wilburt C. Davison Distinguished Professor
Dr. Permar's work focuses on the development of vaccines to prevent vertical transmission of neonatal viral pathogens. She has utilized the nonhuman primate model of HIV/AIDS to characterize the virus-specific immune responses and virus evolution in breast milk and develop a maternal vaccine regimen for protection against breast milk transmission of HIV. In addition, Dr. Permar's lab has advanced the understanding of HIV-specific immune responses and virus evolution in vertically-transmitting an
Saunders

Kevin O'Neil Saunders

Associate Professor in Surgery
The Saunders laboratory aims to understand the immunology of HIV-1 antibodies and the molecular biology of their interaction with HIV-1 envelope (Env) glycoprotein. Our overall goal is to develop protective antibody-based vaccines; therefore, the laboratory has two sections–antibody repertoire analysis and immunogen design. Our research premise is that vaccine-elicited antibodies will broadly neutralize HIV-1 if they can bind directly to the host glycans on Env. However, Env glycans are
Shen

Xiaoying Shen

Associate Professor in Surgery
Tomaras

Georgia Doris Tomaras

Professor in Surgery
Dr. Georgia Tomaras is a tenured Professor of Surgery, Professor of Immunology, Professor of Molecular Genetics and Microbiology and is a Fellow of the American Academy of Microbiology (AAM) and a Fellow of the American Association for the Advancement of Science (AAAS).  Dr. Tomaras is the Director of the Duke Center for AIDS Research, a founding Director of the Duke Center for Human Systems Immunology, the Director of Lab Science and mPI for the HIV Vaccine Trials Ne
Wiehe

Kevin J Wiehe

Associate Professor in Medicine
Williams

Wilton Bryan Williams

Associate Professor in Surgery
Dr. Williams completed a PhD in Biomedical Sciences (Immunology and Microbiology) from the University of Florida and did his postdoctoral work in the laboratory of Dr. Barton Haynes at the Duke Human Vaccine Institute (DHVI). The key goals of HIV vaccine development are to define the host-virus events during natural HIV infection that lead to the induction of broadly neutralizing antibodies, and to recreate those events with a vaccine. As a junior faculty member in the DHVI, Dr. W
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