About

Dan H. Barouch, M.D., Ph.D., is the Director of the Center for Virology and Vaccine Research at Beth Israel Deaconess Medical Center and holds the position of William Bosworth Castle Professor of Medicine and Professor of Immunology at Harvard Medical School. His laboratory focuses on studying the immunology and pathogenesis of viral infections and developing novel vaccine and treatment strategies. He has led the development of vaccine candidates for multiple pathogens of global significance, including HIV, Zika virus, tuberculosis, and SARS-CoV-2. His team has been instrumental in constructing adenovirus vectors, mosaic immunogens, and Env proteins, and evaluating these vaccine candidates in preclinical and clinical studies, including Phase 3 clinical efficacy trials. Notably, his work contributed to the development of the Johnson & Johnson Ad26.COV2.S vaccine for COVID-19. Dr. Barouch's research has been supported by numerous NIH grants and Gates Foundation consortium grants, and he is a key part of the Bill & Melinda Gates Foundation Collaboration for AIDS Vaccine Discovery and the Ragon Institute of MGH, MIT, and Harvard.

Research topics

• Immunology
• Medicine
• Biology
• Virology
• Internal medicine
• Genetics
• Computational biology
• Pathology
• Environmental health
• Gastroenterology
• Obstetrics
• Pediatrics

Selected publications

• Neutralization titer biomarker for antibody-mediated prevention of HIV-1 acquisition

  Nature Medicine · 2022 · 118 citations

  • Immunology
  • Virology
  • Biology

  biomarker as a surrogate endpoint for evaluatinon of bnAb regimens, and as a tool for benchmarking candidate bnAb-inducing vaccines.

  DOI

• Efficacy and safety of a single dose of casirivimab and imdevimab for the prevention of COVID-19 over an 8-month period: a randomised, double-blind, placebo-controlled trial

  The Lancet Infectious Diseases · 2022 · 41 citations

  • Medicine
  • Internal medicine
  • Pediatrics
  DOI

• Safety and Efficacy of Single-Dose Ad26.COV2.S Vaccine against Covid-19

  New England Journal of Medicine · 2021 · 2590 citations

  • Medicine
  • Internal medicine
  • Gastroenterology

  BACKGROUND: The Ad26.COV2.S vaccine is a recombinant, replication-incompetent human adenovirus type 26 vector encoding full-length severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein in a prefusion-stabilized conformation. METHODS: viral particles) or placebo. The primary end points were vaccine efficacy against moderate to severe-critical coronavirus disease 2019 (Covid-19) with an onset at least 14 days and at least 28 days after administration among participants in the per-protocol population who had tested negative for SARS-CoV-2. Safety was also assessed. RESULTS: The per-protocol population included 19,630 SARS-CoV-2-negative participants who received Ad26.COV2.S and 19,691 who received placebo. Ad26.COV2.S protected against moderate to severe-critical Covid-19 with onset at least 14 days after administration (116 cases in the vaccine group vs. 348 in the placebo group; efficacy, 66.9%; adjusted 95% confidence interval [CI], 59.0 to 73.4) and at least 28 days after administration (66 vs. 193 cases; efficacy, 66.1%; adjusted 95% CI, 55.0 to 74.8). Vaccine efficacy was higher against severe-critical Covid-19 (76.7% [adjusted 95% CI, 54.6 to 89.1] for onset at ≥14 days and 85.4% [adjusted 95% CI, 54.2 to 96.9] for onset at ≥28 days). Despite 86 of 91 cases (94.5%) in South Africa with sequenced virus having the 20H/501Y.V2 variant, vaccine efficacy was 52.0% and 64.0% against moderate to severe-critical Covid-19 with onset at least 14 days and at least 28 days after administration, respectively, and efficacy against severe-critical Covid-19 was 73.1% and 81.7%, respectively. Reactogenicity was higher with Ad26.COV2.S than with placebo but was generally mild to moderate and transient. The incidence of serious adverse events was balanced between the two groups. Three deaths occurred in the vaccine group (none were Covid-19-related), and 16 in the placebo group (5 were Covid-19-related). CONCLUSIONS: A single dose of Ad26.COV2.S protected against symptomatic Covid-19 and asymptomatic SARS-CoV-2 infection and was effective against severe-critical disease, including hospitalization and death. Safety appeared to be similar to that in other phase 3 trials of Covid-19 vaccines. (Funded by Janssen Research and Development and others; ENSEMBLE ClinicalTrials.gov number, NCT04505722.).

  DOI

• Engineered SARS-CoV-2 receptor binding domain improves manufacturability in yeast and immunogenicity in mice

  Proceedings of the National Academy of Sciences · 2021 · 100 citations

  • Virology
  • Biology
  • Immunology

  Global containment of COVID-19 still requires accessible and affordable vaccines for low- and middle-income countries (LMICs). Recently approved vaccines provide needed interventions, albeit at prices that may limit their global access. Subunit vaccines based on recombinant proteins are suited for large-volume microbial manufacturing to yield billions of doses annually, minimizing their manufacturing cost. These types of vaccines are well-established, proven interventions with multiple safe and efficacious commercial examples. Many vaccine candidates of this type for SARS-CoV-2 rely on sequences containing the receptor-binding domain (RBD), which mediates viral entry to cells via ACE2. Here we report an engineered sequence variant of RBD that exhibits high-yield manufacturability, high-affinity binding to ACE2, and enhanced immunogenicity after a single dose in mice compared to the Wuhan-Hu-1 variant used in current vaccines. Antibodies raised against the engineered protein exhibited heterotypic binding to the RBD from two recently reported SARS-CoV-2 variants of concern (501Y.V1/V2). Presentation of the engineered RBD on a designed virus-like particle (VLP) also reduced weight loss in hamsters upon viral challenge.

  PublisherOA PDFDOI

• Profiling SARS-CoV-2 HLA-I peptidome reveals T cell epitopes from out-of-frame ORFs

  Cell · 2021 · 165 citations

  • Biology
  • Virology
  • Computational biology
  PublisherOA PDFDOI

• Assessment of Maternal and Neonatal SARS-CoV-2 Viral Load, Transplacental Antibody Transfer, and Placental Pathology in Pregnancies During the COVID-19 Pandemic

  JAMA Network Open · 2020 · 438 citations

  • Medicine
  • Immunology
  • Virology

  Importance: Biological data are lacking with respect to risk of vertical transmission and mechanisms of fetoplacental protection in maternal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Objective: To quantify SARS-CoV-2 viral load in maternal and neonatal biofluids, transplacental passage of anti-SARS-CoV-2 antibody, and incidence of fetoplacental infection. Design, Setting, and Participants: This cohort study was conducted among pregnant women presenting for care at 3 tertiary care centers in Boston, Massachusetts. Women with reverse transcription-polymerase chain reaction (RT-PCR) results positive for SARS-CoV-2 were recruited from April 2 to June 13, 2020, and follow-up occurred through July 10, 2020. Contemporaneous participants without SARS-CoV-2 infection were enrolled as a convenience sample from pregnant women with RT-PCR results negative for SARS-CoV-2. Exposures: SARS-CoV-2 infection in pregnancy, defined by nasopharyngeal swab RT-PCR. Main Outcomes and Measures: The main outcomes were SARS-CoV-2 viral load in maternal plasma or respiratory fluids and umbilical cord plasma, quantification of anti-SARS-CoV-2 antibodies in maternal and cord plasma, and presence of SARS-CoV-2 RNA in the placenta. Results: Among 127 pregnant women enrolled, 64 with RT-PCR results positive for SARS-CoV-2 (mean [SD] age, 31.6 [5.6] years) and 63 with RT-PCR results negative for SARS-CoV-2 (mean [SD] age, 33.9 [5.4] years) provided samples for analysis. Of women with SARS-CoV-2 infection, 23 (36%) were asymptomatic, 22 (34%) had mild disease, 7 (11%) had moderate disease, 10 (16%) had severe disease, and 2 (3%) had critical disease. In viral load analyses among 107 women, there was no detectable viremia in maternal or cord blood and no evidence of vertical transmission. Among 77 neonates tested in whom SARS-CoV-2 antibodies were quantified in cord blood, 1 had detectable immunoglobuilin M to nucleocapsid. Among 88 placentas tested, SARS-CoV-2 RNA was not detected in any. In antibody analyses among 37 women with SARS-CoV-2 infection, anti-receptor binding domain immunoglobin G was detected in 24 women (65%) and anti-nucleocapsid was detected in 26 women (70%). Mother-to-neonate transfer of anti-SARS-CoV-2 antibodies was significantly lower than transfer of anti-influenza hemagglutinin A antibodies (mean [SD] cord-to-maternal ratio: anti-receptor binding domain immunoglobin G, 0.72 [0.57]; anti-nucleocapsid, 0.74 [0.44]; anti-influenza, 1.44 [0.80]; P < .001). Nonoverlapping placental expression of SARS-CoV-2 receptors angiotensin-converting enzyme 2 and transmembrane serine protease 2 was noted. Conclusions and Relevance: In this cohort study, there was no evidence of placental infection or definitive vertical transmission of SARS-CoV-2. Transplacental transfer of anti-SARS-CoV-2 antibodies was inefficient. Lack of viremia and reduced coexpression and colocalization of placental angiotensin-converting enzyme 2 and transmembrane serine protease 2 may serve as protective mechanisms against vertical transmission.

  DOI

• Potently neutralizing and protective human antibodies against SARS-CoV-2

  Nature · 2020 · 1190 citations

  • Virology
  • Immunology
  • Medicine
  DOI

Recent grants

• NIH Grant UM1AI100663

  NIH · $270.8M · 2020

• Optimization of Broadly Neutralizing Antibodies for HIV Eradication

  NIH · $3.6M · 2017–2023

• NIH Grant R01AI058727

  NIH · $2.0M · 2010

• NIH Grant R01AI066924

  NIH · $3.5M · 2012

• NIH Grant P51RR000168

  NIH · $79.8M · 2013

Frequent coauthors

• Michael S. Seaman

  Beth Israel Deaconess Medical Center

  224 shared

• Norman L. Letvin

  206 shared

• Catherine Jacob-Dolan

  Beth Israel Deaconess Medical Center

  194 shared

• Jinyan Liu

  Southeast University

  194 shared

• Jingyou Yu

  Harvard University

  187 shared

• Michelle A. Lifton

  Beth Israel Deaconess Medical Center

  180 shared

• Amanda J. Martinot

  172 shared

• Erica N. Borducchi

  Beth Israel Deaconess Medical Center

  164 shared

Labs

• Clinical Trials UnitPI

Education

• Ph.D., Immunology

  Harvard University

  1998

• M.D.

  Harvard Medical School

  1993

• B.S., Biology

  University of Pennsylvania

  1989

Awards & honors

• 2023 Paragon Award for Research Excellence from the Doris Du…
• The Heroes Among Us Award (2021)

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