About

Christopher O. Barnes, PhD, is the Principal Investigator of the Barnes Lab at Stanford. His research focuses on understanding biological processes through various scientific disciplines, including biophysics, immunology, genetics, and molecular and cellular physiology. Dr. Barnes leads a team of staff scientists, postdoctoral fellows, graduate students, and research technicians dedicated to advancing knowledge in these areas. His lab is engaged in multidisciplinary research efforts, with team members working on projects that span from biophysical studies to immunological and genetic investigations. Dr. Barnes's leadership involves guiding research initiatives, mentoring students and staff, and contributing to the scientific community through his expertise and collaborative efforts.

Research topics

• Biology
• Virology
• Immunology
• Medicine
• Genetics
• Internal medicine
• Social Science
• Sociology
• Computational biology
• Physics
• Gastroenterology
• Environmental ethics
• Chemistry
• Engineering ethics
• Optics
• Gender studies

Selected publications

• BPS2026 – Structural insights into germline antibody intermediates guide HIV-1 immunogen design

  Biophysical Journal · 2026-02-01

  articleSenior author
  PublisherDOI

• BPS2026 – Structure-guided computational engineering of prefusion-stabilized alphacoronavirus S2 immunogens

  Biophysical Journal · 2026-02-01

  articleSenior author
  PublisherDOI

• Oriented Multivalent Display Drives Consistent Serum Immunodominance to the Ebola Virus Glycoprotein

  ACS Central Science · 2026-01-09

  articleOpen access

  Despite the vast diversity of B cell repertoires, serum antibody responses during viral infection often focus on a limited set of epitopesa phenomenon known as immunodominance. This inherent bias establishes a hierarchy of epitope responses, which often facilitates viral immune evasion and presents a major challenge for universal vaccine design. It remains unclear whether serum immunodominance is primarily driven by antigen-intrinsic properties or by the spatial constraints imposed by virion-bound antigen presentation. Here, using Ebola virus glycoprotein (GP) as a model system, we found that trimeric GP elicited varied epitope hierarchies between individual animals during primary immunization. In contrast, multivalent GP presentation on either a vesicular stomatitis virus or ferritin nanoparticlesin the native orientation found on the Ebola viruselicited highly consistent and more refined epitope hierarchies across multiple mice and guinea pigs. These findings reveal a key role of oriented multivalent presentation in shaping serum immunodominance. The striking consistency of epitope hierarchy among individuals suggests that oriented multivalent presentation may promote more uniform immune protection at the population level, beyond increasing the magnitude of antibody binding and neutralizing responses.

  PublisherDOI

• Human antibodies against West Nile and related orthoflaviviruses

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-04-06

  articleOpen access

  West Nile virus (WNV) is a mosquito-borne pathogen of global concern that can cause fatal neuroinvasive disease. No specific prophylaxis or treatment exists for WNV or related orthoflavivirus infections, and the determinants of human disease severity remain poorly understood. Here, we report that neutralizing autoantibodies against type I interferons do not impair antiviral antibody development. Among the fully human monoclonal antibodies with potent neutralizing activity against WNV that were discovered, W010 targets a unique epitope within the envelope protein domain III (EDIII) and confers both pre- and post-exposure protection in a murine WNV model, even when interferon signaling is impaired. A second protective antibody, W014, exhibits broad cross-neutralization of other pathogenic orthoflavivirus members, including Japanese encephalitis virus, Murray Valley encephalitis virus, Saint Louis encephalitis virus, and Usutu virus. These findings identify key neutralizing epitopes on WNV EDIII and provide candidates for the development of antibody-based interventions against encephalitic orthoflavivirus infections.

  PublisherDOI

• A Customized Defense: Bispecific Antibodies Binding Functional Domains in the S1 and S2 Subunits of the SARS-CoV-2 Spike Glycoprotein

  Stanford Digital Repository · 2026-05-01

  articleOpen access

  As evidenced by the COVID-19 pandemic, the causative virus, SARS-CoV-2, is at the root of global health emergencies and continues to spread, posing various threats to human health. The continuous evolution of SARS-CoV-2 drives the emergence of different variants of concern (VOCs) that evade many existing antibody therapeutics. The viral spike (S) glycoprotein remains a primary target due to its essential role in mediating membrane fusion and viral entry into host cells. This study tests the hypothesis that simultaneously targeting multiple epitopes on the S protein enhances neutralization potency and breadth. Accordingly, specificities for two distinct epitopes on the S protein, the amino-terminal domain (NTD) and receptor binding domain (RBD), were first combined using bispecific antibodies (bsAbs) designed to increase avidity and limit viral escape from selective pressure. The bsAb constructs were designed and engineered by subcloning single-chain variable fragments (scFvs) derived from previously identified antibodies into tandem formats, with expression in mammalian cells. In this project, binding to a broad panel of variants was characterized using enzyme-linked immunosorbent assays (ELISAs) and biolayer interferometry (BLI), followed by subsequent evaluation of neutralization potency using lentiviral pseudotype assays. Remarkably, the bsAbs retained neutralization efficacy against divergent Omicron VOCs, outperforming the reduced potency seen for monoclonal antibodies. This bispecific strategy was extended to conserved epitopes shared across SARS-CoV-2 VOCs and the main coronavirus genera, termed coldspots, within the Stem Helix (SH) and Lower Stalk (LS). We additionally resolved the X-ray crystal structure of a LS Fab, expanding the limited structural knowledge about antibodies to this region and guiding subsequent LS-directed investigation. The same principle demonstrated by NTD-RBD constructs did not translate for the LS-SH bsAbs, suggesting the biological mechanisms governing these epitopes remain insufficiently understood and warrant further study to guide bsAb design. Collectively, this study provides a framework for next-generation bsAbs, highlighting the therapeutic potential of NTD-RBD designs while informing future optimization of coldspot targeting strategies against current and future coronavirus strains.

  PublisherDOI

• Correction to “Oriented Multivalent Display Drives Consistent Serum Immunodominance to the Ebola Virus Glycoprotein”

  ACS Central Science · 2026-02-03

  articleOpen access

  [This corrects the article DOI: 10.1021/acscentsci.5c01886.].

  PublisherDOI

• BPS2026 – Identifying key interactions of monoclonal antibodies that target the HuCoV-HKU1 spike using cryo-EM

  Biophysical Journal · 2026-02-01

  articleSenior author
  PublisherDOI

• Human antibodies against West Nile virus and related Orthoflaviviruses 9100

  The Journal of Immunology · 2025-11-01

  articleOpen access

  Abstract Description West Nile virus (WNV), a member of the Orthoflavivirus genus, can cause fatal encephalitis in humans. With no specific treatment available, WNV remains the leading cause of mosquito-borne disease in the continental United States, spreading globally. The antiviral antibody response is important for protection against WNV disease, while anti-interferon type I (IFN-I) autoantibodies have been linked to higher risk of WNV encephalitis. We show that the presence of anti-IFN-I autoantibodies does not impair the development of antiviral antibodies in individuals with WNV neuroinvasive disease. From selected convalescent individuals with high WNV serum neutralizing activity we isolated W010, a potent monoclonal antibody targeting the virus envelope domain III (EDIII). In a lethal mouse model, W010 provides significant protection even at low doses and when administered up to five days post-infection. Unlike previously reported antibodies, W010 is highly effective against both lineages of WNV that cause human disease. Other EDIII-specific antibodies that were discovered are broadly cross-reactive, also neutralizing other members of the Japanese encephalitis virus serocomplex in vitro (JEV, Murray Valley encephalitis virus, Saint Louis encephalitis virus, and Usutu virus). Thus, human pan-neutralizing antibodies exist that simultaneously protect against viruses of the JEV-serocomplex. The structural basis of neutralization by the lead antibodies for clinical development is revealed. Funding Sources Swiss National Science Foundation (no. 310030L_196866), NIH U01 AI151698 Topic Categories Vaccines and Immunotherapy (VAC)

  PublisherOA PDFDOI

• Juneteenth in STEMM and the barriers to equitable science

  UNC Libraries · 2025-03-19

  articleOpen access
  PublisherDOI

• BPS2025 - Structure-guided engineering of flavivirus nonstructural protein 1

  Biophysical Journal · 2025-02-01

  articleSenior author
  PublisherDOI

Recent grants

• The roles of TFIIB and TFIIF in transcription by DNA-directed RNA Polymerase II

  NIH · $43k · 2015–2016

Frequent coauthors

• Michel C. Nussenzweig

  Howard Hughes Medical Institute

  76 shared

• Paul D. Bieniasz

  Rockefeller University

  56 shared

• Pamela J. Björkman

  California Institute of Technology

  45 shared

• Daniel Růžek

  Veterinary Research Institute

  28 shared

• Frauke Muecksch

  University Hospital Heidelberg

  26 shared

• Théodora Hatziioannou

  Rockefeller University

  26 shared

• Pavel Svoboda

  Centers for Disease Control and Prevention

  25 shared

• Morgan E. Abernathy

  Stanford University

  22 shared

Labs

• Barnes Lab at StanfordPI

Education

• PhD, Pharmacology and Chemical Biology

  University of Pittsburgh

  2016

• BS, BA, MA, Chemistry

  University of North Carolina at Chapel Hill

  2010

Awards & honors

• Rita Allen Foundation Scholar
• HHMI Hanna H. Gray Fellow
• Chan Zuckerberg Biohub investigator