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Articles by Dan Barouch
Tissue origins and immune correlates of viral rebound in SIV-infected rhesus macaques after ART discontinuation
Abstract Supplementary Materials REFERENCES AND NOTES Information & Authors Metrics & Citations Check Access References Figures Tables Media Share This article has 0 eLetter . Abstract Most persons living with HIV-1 who discontinue antiretroviral therapy (ART) demonstrate viral rebound, but the tissue-level events that lead to rebound viremia remain poorly understood.
Am80-lipid nanoparticles serve as an enteric mucosal adjuvant following parenteral immunization with inactivated polio vaccine
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Abstract INTRODUCTION RESULTS DISCUSSION MATERIALS AND METHODS Acknowledgments Supplementary Materials REFERENCES Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract Enteric pathogens are a major contributor to the global disease burden, necessitating vaccines capable of inducing robust gastrointestinal mucosal immunity.
By Yentli E. Soto Albrecht, Oded Liran, Roddy M. Grieves, Behnaz Eshaghi, Erika Yan Wang, Sevinj Mursalova, Timothy A Forster, Ninaad Lasrado, Jinbi Tian, Dorin Artzi, Stacey Lin, Zongting Wu, Xin Yang, Wontaek Chung, Ilin Sadeghi, Johnny Garcia, Ziqi Chen, Olivia Sheridan, Alicia Lau, Bernardo A. Mainou, Kathryn Jones, Yi Liu, Dan Barouch, Aki Gurram, Ulrich von Andrian
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Science Magazine
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Initial sites of SIV rebound after antiretroviral treatment cessation in rhesus macaques - Nature Microbiology
Abstract The tissue origin(s) and the earliest viral dynamics of HIV rebound after antiretroviral therapy (ART) remain unclear. Here, using barcoded SIVmac239 in rhesus macaques (n = 24), we defined the distribution of barcode-specific viral RNA expression in tissues during ART (n = 6) and then assessed initial clonal rebound 5 and 7 days after ART cessation by identifying barcodes in individual tissues that exceeded the 99th percentile of the on-ART distribution (‘outliers’).
Anti-IL-15 treatment reduces acute lentivirus inflammation and signaling in the brain
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Keywords HAND SIV IL-15 microglia neuroinflammation CNS immune response Introduction Despite advancements in viral suppression with antiretroviral therapies, HIV-associated neurocognitive disorder (HAND) remains an ongoing chronic health problem in approximately half of people living with HIV (PLWH) worldwide.1,2 HIV infects the brain within days during the acute phase of infection and causes neurological symptoms.3 Viral entry into the central nervous system (CNS) elicits an early immune...
By Daniel R. Ram, Raja Gopalakrishnan, Malika Aid, Kyle Kroll, Caitlin Davis, Marco M. Hefti, Kimberly L. Fiock, Christine M. Fennessey, Noe B. Mercado, Rhianna Jones, Griffin Woolley, Valerie Varner, Michelle Lifton, Steven E. Bosinger, Dan Barouch, Brandon F. Keele, R. Keith Reeves, C. Sabrina Tan, Jasmine Miftahof, Omar Aristizabal, Eunice Kayitare Gikundiro, Brook Tilahun, Yvette Umutoniwase, Kate Loidolt, Victoria Harper-Alexander
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Cell Reports Medicine
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Multi-scaled transcriptomics of chronically inflamed nasal epithelium reveals immune-epithelial dynamics and tissue remodeling in nasal polyp formation
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Keywords spatial transcriptomics single-cell nasal epithelium inflammation chronic rhinosinusitis remodeling autoimmunity nasal polyp type 2 inflammation Introduction Chronic rhinosinusitis (CRS) is a heterogeneous inflammatory disease of the nasal and sinonasal cavities.
By Guanrui Liao, Tsuguhisa Nakayama, Bokai Zhu, Ivan Lee, Jason Yeung, Yao Yu Yeo, Yuzhou Chang, Cankun Wang, Steven Liao, Dingani Nkosi, Axel E. Renteria, Dawn T. Bravo, Jonathan B. Overdevest, Carol H. Yan, David Zarabanda, Philip Gall, Sachi S. Dholakia, Nicole A. Borchard, Angela Yang Verified, Dayoung Kim, Zara Patel, Peter Hwang, Dhananjay Wagh, Katie Phillips, Michael Chang, Matt Lechner, Zihai Li, Te-Huei Yeh, Garry P. Nolan, Maria Serena Longhi, Vassiliki A Boussiotis, Dan Barouch, Qin Ma, Jayakar V. Nayak, Sizun Jiang, John Coller
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Cell Press
Verified
Mosaic HIV-1 vaccine and SHIV challenge strain V2 loop sequence identity and protection in primates - npj Vaccines
Abstract The failure of human vaccine efficacy trials assessing a mosaic HIV-1 vaccine calls into question the translatability of preclinical SHIV challenge studies that demonstrated high efficacy of this vaccine in primates. Here we present a post hoc immune correlates analysis of HIV-1 Env peptide-binding antibody responses from the NHP13-19 study identifying the V2 loop as the principal correlate of protection in primates.
Graph Fourier transform for spatial omics representation and analyses of complex organs - Nature Communications
Abstract Spatial omics technologies decipher functional components of complex organs at cellular and subcellular resolutions. We introduce Spatial Graph Fourier Transform (SpaGFT) and apply graph signal processing to a wide range of spatial omics profiling platforms to generate their interpretable representations.
Graph Fourier transform for spatial omics representation and analyses of complex organs
Culture 11 hours ago Found an arrowhead in Kansas? Archaeologist urges you to leave it alone ksn.com - by: Matthew Self • 11h TOPEKA, Kan.
Journal of the International AIDS Society | IAS HIV Research Journal | Wiley Online Library
The number of new HIV acquisitions globally has declined, but not rapidly enough to meet the 2030 targets set by UNAIDS and the United Nations Sustainable Development Goals (SDGs) [1, 2]. Despite intense efforts such as those to support the UNAIDS 95-95-95 targets and to expand the availability of oral pre-exposure prophylaxis (PrEP), progress in primary prevention of HIV acquisition has lagged.
Modeling resistance to the broadly neutralizing antibody PGT121 in people living with HIV-1
Loading metrics Open Access Peer-reviewed Research Article ? This is an uncorrected proof. Citation: Cassidy T, Stephenson KE, Barouch DH, Perelson AS (2024) Modeling resistance to the broadly neutralizing antibody PGT121 in people living with HIV-1. PLoS Comput Biol 20(3): e1011518.
Global variation in prior exposure shapes antibody neutralization profiles of SARS-CoV-2 variants up to BA.2.86
Abstract The highly mutated SARS-CoV-2 variant, BA.2.86, and its descendants are now the most frequently sequenced variants of SARS-CoV-2. We analyze antibody neutralization data from eight laboratories from the UK, USA, Denmark, and China, including two datasets assessing the effect of XBB.1.5 vaccines, to determine the effect of infection and vaccination history on neutralization of variants up to and including BA.2.86, and produce antibody landscapes to describe these neutralization profiles.
Prophylactic HIV-1 vaccine trials: past, present, and future
1. Gallo RC Sarin PS Gelmann EP et al. Isolation of human T-cell leukemia virus in acquired immune deficiency syndrome (AIDS). Science. 1983; 220: 865-867 2. Barré-Sinoussi F Chermann JC Rey F et al. Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS). Science. 1983; 220: 868-871 3. Fact sheet – latest global and regional statistics on the status of the AIDS epidemic. 4.
Peripheral blood biomarkers predict viral rebound following antiretroviral therapy discontinuation in SIV-infected, early ART-treated rhesus macaques
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A microneedle vaccine printer for thermostable COVID-19 mRNA vaccines - Nature Biotechnology
Abstract Decentralized manufacture of thermostable mRNA vaccines in a microneedle patch (MNP) format could enhance vaccine access in low-resource communities by eliminating the need for a cold chain and trained healthcare personnel. Here we describe an automated process for printing MNP Coronavirus Disease 2019 (COVID-19) mRNA vaccines in a standalone device.
Booster with Ad26.COV2.S or Omicron-adapted vaccine enhanced immunity and efficacy against SARS-CoV-2 Omicron in macaques - Nature Communications
Abstract Omicron spike (S) encoding vaccines as boosters, are a potential strategy to improve COVID-19 vaccine efficacy against Omicron. Here, macaques (mostly females) previously immunized with Ad26.COV2.S, are boosted with Ad26.COV2.S, Ad26.COV2.S.529 (encoding Omicron BA.1 S) or a 1:1 combination of both vaccines. All booster vaccinations elicit a rapid antibody titers increase against WA1/2020 and Omicron S.
Carbohydrate fatty acid monosulphate: oil-in-water adjuvant enhances SARS-CoV-2 RBD nanoparticle-induced immunogenicity and protection in mice - npj Vaccines
Abstract Development of SARS-CoV-2 vaccines that protect vulnerable populations is a public health priority. Here, we took a systematic and iterative approach by testing several adjuvants and SARS-CoV-2 antigens to identify a combination that elicits antibodies and protection in young and aged mice. While demonstrating superior immunogenicity to soluble receptor-binding domain (RBD), RBD displayed as a protein nanoparticle (RBD-NP) generated limited antibody responses.
Neutralization Escape by SARS-CoV-2 Omicron Subvariant BA.4.6
To the Editor: Figure 1.
Covid-19 Vaccines — Immunity, Variants, Boosters | NEJM
Figure 3. In the spring of 2020, the predominant global form of the original virus rapidly transitioned to a variant that carried four mutations in the SARS-CoV-2 genome, including a single D614G point mutation in the spike protein that conferred a fitness advantage.58,59 Subsequently, multiple waves of SARS-CoV-2 variants have emerged that replaced prior variants, with new variants often showing increased transmissibility and greater antibody escape (Figure 3).
Neutralization titer biomarker for antibody-mediated prevention of HIV-1 acquisition - Nature Medicine
Abstract The Antibody Mediated Prevention trials showed that the broadly neutralizing antibody (bnAb) VRC01 prevented acquisition of human immunodeficiency virus-1 (HIV-1) sensitive to VRC01. Using AMP trial data, here we show that the predicted serum neutralization 80% inhibitory dilution titer (PT80) biomarker—which quantifies the neutralization potency of antibodies in an individual’s serum against an HIV-1 isolate—can be used to predict HIV-1 prevention efficacy.
Therapeutic efficacy of combined active and passive immunization in ART-suppressed, SHIV-infected rhesus macaques - Nature Communications
Abstract The latent viral reservoir is the critical barrier for developing an HIV-1 cure. Previous studies have shown that therapeutic vaccination or broadly neutralizing antibody (bNAb) administration, together with a Toll-like receptor 7 (TLR7) agonist, enhanced virologic control or delayed viral rebound, respectively, following discontinuation of antiretroviral therapy (ART) in SIV- or SHIV-infected rhesus macaques.
Safety and antiviral activity of triple combination broadly neutralizing monoclonal antibody therapy against HIV-1: a phase 1 clinical trial - Nature Medicine
Abstract HIV-1 therapy with single or dual broadly neutralizing antibodies (bNAbs) has shown viral escape, indicating that at least a triple bNAb therapy may be needed for robust suppression of viremia.
Vaccines Elicit Highly Conserved Cellular Immunity to SARS-CoV-2 Omicron - Nature
Vaccines Elicit Highly Conserved Cellular Immunity to SARS-CoV-2 Omicron Jinyan Liu1 na1, ORCID: orcid.org/0000-0001-7821-55521 na1, Daniel Sellers1 na1, Julia Barrett1, ORCID: orcid.org/0000-0001-6641-03421,2, Michelle Lifton ORCID: orcid.org/0000-0003-0279-21981, Katherine McMahan1, Michaela Sciacca1, Haley VanWyk1, Cindy Wu1, Jingyou Yu1, Ai-ris Y. Collier ORCID: orcid.org/0000-0002-8539-39601 & Dan H.
J&J COVID vaccine researcher: US 'can't be safe' until entire world is vaccinated
August 16, 2021 3 min read Save Source/Disclosures Published by: Source: Barouch D. COVID-19: Developing a Vaccine During a Pandemic. Presented at: Association of Women in Rheumatology Annual Conference; August 12-15, 2021, Hilton Head Island, South Carolina (hybrid meeting). Disclosures: Barouch reports no relevant financial disclosures. ADD TOPIC TO EMAIL ALERTS Receive an email when new articles are posted on Please provide your email address to receive an email when new articles are posted on .
Subcutaneous REGEN-COV Antibody Combination to Prevent Covid-19
Supported by Regeneron Pharmaceuticals, F. Hoffmann–La Roche, cooperative agreement awards from the National Institute of Allergy and Infectious Diseases, NIH, and a grant (UM1AI068619) from the Covid-19 Prevention Network. Disclosure forms provided by the authors are available with the full text of this article at NEJM.org. The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health (NIH).
Durable Humoral and Cellular Immune Responses 8 Months after Ad26.COV2.S Vaccination
3 Citing Articles Related Articles To the Editor: Interim immunogenicity and efficacy data for the Ad26.COV2.S vaccine (Johnson & Johnson–Janssen) against coronavirus disease 2019 (Covid-19) have recently been reported.1-3 We describe here the 8-month durability of humoral and cellular immune responses in 20 participants who received the Ad26.COV2.S vaccine in one or two doses (either 5×1010 viral particles or 1011 viral particles) and in 5 participants who received placebo.2 We evaluated...
Compromised Humoral Functional Evolution Tracks with SARS-CoV-2 Mortality
Highlights • IgA and IgM evolve rapidly across all levels of disease severity • Rapid and potent IgG class switching is linked to survival • Moderate disease is associated with a delay but ultimate convergence of IgG • Early S2-cross-reactivity is linked to survival after severe disease Summary The urgent need for an effective SARS-CoV-2 vaccine has forced development to progress in the absence of well-defined correlates of immunity.
Approaches and Challenges in SARS-CoV-2 Vaccine Development
Gabriel Dagotto ∗ Author Footnotes ∗ These authors contributed equally to this work Gabriel Dagotto Footnotes ∗ These authors contributed equally to this work Affiliations Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA 02215, USAHarvard Medical School, Boston, MA 02115, USA Search for articles by this author Jingyou Yu ∗ Author Footnotes ∗ These authors contributed equally to this work Jingyou Yu Footnotes ∗ These authors contributed equally to this...
Vaccines and Broadly Neutralizing Antibodies for HIV-1 Prevention
Annual Review of Immunology Vol. 38:673-703 (Volume publication date April 2020) https://doi.org/10.1146/annurev-immunol-080219-023629 Kathryn E. Stephenson,1,2,* Kshitij Wagh,3,4,* Bette Korber,3,4 and Dan H.
Recommendations for analytical antiretroviral treatment interruptions in HIV research trials-report of a consensus meeting
Summary Analytical antiretroviral treatment interruption (ATI) is an important feature of HIV research, seeking to achieve sustained viral suppression in the absence of antiretroviral therapy (ART) when the goal is to measure effects of novel therapeutic interventions on time to viral load rebound or altered viral setpoint. Trials with ATIs also intend to determine host, virological, and immunological markers that are predictive of sustained viral control off ART.
T cell subset differentiation and antibody responses following antiretroviral therapy during SIV infection
Antiretroviral therapy (ART) for the treatment of human immunodeficiency virus (HIV) infection represents a major breakthrough in the treatment of HIV/AIDS. However, it remains unclear how ART influences virus‐specific immune responses. Understanding how ART influences virus‐specific immune responses is important for developing novel cure and eradication interventions for HIV‐1.
Immune Correlate-Guided HIV Vaccine Design
Although vaccines have been successfully developed against several pathogens, designing an effective vaccine to protect against human immunodeficiency virus (HIV) has remained an intractable challenge. To address this, the research community has looked to human and non-human primate studies to understand the correlates of protective immunity, based on which a targeted vaccine strategy may be designed. Two distinct approaches, focused on different immune correlates of protection, have emerged.
A step forward for HIV vaccines
Development of a safe and effective HIV vaccine will probably be essential to achieve a durable end to the HIV pandemic.1x1Fauci, AS. An HIV vaccine is essential for ending the HIV/AIDS pandemic. JAMA. 2017; 318: 1535–1536Crossref | PubMed | Scopus (4) | Google ScholarSee all References, 2x2Stephenson, KE, D'Couto, HT, and Barouch, DH. New concepts in HIV-1 vaccine development. Curr Opin Immunol.
Zika virus vaccines
Satterfield-Nash, A. et al. Health and development at age 19–24 months of 19 children who were born with microcephaly and laboratory evidence of congenital Zika virus infection during the 2015 Zika virus outbreak — Brazil, 2017. MMWR Morb. Mortal. Wkly Rep. 66, 1347–1351 (2017). van der Linden, V. et al. Description of 13 infants born during October 2015–January 2016 with congenital Zika virus infection without microcephaly at birth — Brazil. MMWR Morb. Mortal. Wkly Rep. 65, 1343–1348 (2016). Ulmer, J.
HIV-1 Latency by Transition
Antiretroviral therapy (ART) has revolutionized HIV-1 treatment but does not cure HIV-1 infection, and plasma viremia rebounds in the majority of HIV-1-infected individuals when ART is stopped. HIV-1 establishes a pool of long-lived memory CD4+ T cells in which replication-competent virus persists as integrated proviral DNA.
Regulation of CD4 T cells and their effects on immunopathological inflammation following viral infection
CD4 T cells help immune responses, but knowledge of how memory CD4 T cells are regulated and how they regulate adaptive immune responses and induce immunopathology is limited. Using adoptive transfer of virus-specific CD4 T cells, we show that naïve CD4 T cells undergo substantial expansion following infection, but can induce lethal TH1-driven inflammation.
Tight regulation of memory CD4 T cells limits immunopathology following chronic viral infection
CD4 T cells are critical for the induction of adaptive immune responses. Surprisingly, we published a report showing that memory CD4 T cells could also mediate lethal immunopathology following chronic lymphocytic choriomeningitis virus (LCMV) infection. To interrogate whether naive or memory CD4 T cells can similarly mediate immune dysregulation, we transferred equal numbers of naive or memory virus-specific CD4 T cells into naive mice, and infected these with chronic LCMV.
Rapid Inflammasome Activation following Mucosal SIV Infection of Rhesus Monkeys
FiguresFigure 1Viral RNA in TissuesTissue viral RNA (log RNA copies /108 cell equivalents) across multiple tissues at necropsy in animals on days 1, 3, 7, or 10 following inoculation with SIVmac251. The colors on each plot reflect individual animals.
Hyperexpansion of RNA Bacteriophage Diversity
Bacteriophage modulation of microbial populations impacts critical processes in ocean, soil, and animal ecosystems. However, the role of bacteriophages with RNA genomes (RNA bacteriophages) in these processes is poorly understood, in part because of the limited number of known RNA bacteriophage species. Here, we identify partial genome sequences of 122 RNA bacteriophage phylotypes that are highly divergent from each other and from previously described RNA bacteriophages.
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