About

Priyamvada Acharya is a Professor in Surgery and a Professor of Biochemistry at Duke University. She is a member of the Duke Human Vaccine Institute and the Duke Cancer Institute. Her work is associated with the Duke Department of Biochemistry, and she is involved in research activities within these institutes. Her academic and research roles focus on biochemistry, vaccine development, and cancer research, contributing to the scientific community through her expertise and leadership in these fields.

Research topics

• Biology
• Virology
• Medicine
• Immunology
• Genetics
• Computational biology
• Internal medicine
• Molecular biology
• Biochemistry
• Cell biology

Selected publications

• Nonstabilized SARS-CoV-2 spike mRNA vaccination induces broadly neutralizing antibodies in nonhuman primates

  Science Translational Medicine · 2025-06-11 · 1 citations

  articleOpen access

  Immunization with messenger RNA (mRNA) or viral vectors encoding spike protein with diproline substitutions (S-2P) were shown to provide protective immunity, curbing the COVID-19 pandemic. However, in light of the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) that can cause COVID-19, it is essential that we understand how immunization with spike protein elicits neutralizing antibodies (nAbs). Here, we compared immunization of macaques with mRNA vaccines expressing ancestral spike protein with or without diproline substitutions, showing that the diproline substitutions were not required for protection against SARS-CoV-2 challenge or induction of broadly neutralizing B cell lineages. One group of nAbs elicited by the ancestral spike protein lacking diproline substitutions targeted the outer face of the receptor binding domain (RBD), neutralized all tested SARS-CoV-2 VOC pseudotyped viruses including Omicron XBB.1.5 in vitro, but lacked cross-sarbecovirus neutralization. Structural analysis showed that the macaque nAbs that could broadly neutralize VOCs bound to the same epitope as a human nAb, DH1193. In contrast, vaccine-induced antibodies that targeted the RBD inner face neutralized multiple sarbecoviruses, protected mice from bat CoV RsSHC014 challenge, but lacked Omicron variant neutralization. Thus, ancestral SARS-CoV-2 spike mRNA vaccines lacking proline substitutions can induce B cell lineages binding to distinct RBD sites that either broadly neutralize animal and human sarbecoviruses or neutralize recent Omicron VOCs. Thus, the use of a nonstabilized spike protein design in some COVID-19 vaccines does not preclude the elicitation of broad sarbecovirus and broad VOC nAbs.

  PublisherOA PDFDOI

• Conformational trajectory of the HIV-1 fusion peptide during CD4-induced envelope opening

  Nature Communications · 2025-05-17 · 8 citations

  articleOpen accessSenior author

  The hydrophobic fusion peptide (FP), a critical component of the HIV-1 entry machinery, is located at the N terminus of the envelope (Env) gp41 subunit. The receptor-binding gp120 subunit of Env forms a heterodimer with gp41. The gp120/gp41 heterodimer assembles into a homotrimer, in which FP is accessible for antibody binding. Env conformational changes or "opening" that follow receptor binding result in FP relocating to a newly formed interprotomer pocket at the gp41-gp120 interface where it is sterically inaccessible to antibodies. The mechanistic steps connecting the entry-related transition of antibody accessible-to-inaccessible FP configurations remain unresolved. Here, using SOSIP-stabilized Env ectodomains, we visualize that the FP remains accessible for antibody binding despite substantial receptor-induced Env opening. We delineate stepwise Env opening from its closed state to a functional CD4-bound symmetrically open Env in which we show that FP was accessible for antibody binding. We define downstream re-organizations that lead to the formation of a gp120/gp41 cavity into which the FP buries to become inaccessible for antibody binding. These findings improve our understanding of HIV-1 entry and delineate the entry-related conformational trajectory of a key site of HIV vulnerability to neutralizing antibody.

  PublisherOA PDFDOI

• BPS2025 - Rational engineering of HIV-1 Env to enhance recognition of fusion peptide in a glycan dependent manner

  Biophysical Journal · 2025-02-01

  articleSenior author
  PublisherDOI

• Breast milk delivery of an engineered dimeric IgA protects neonates against rotavirus

  Mucosal Immunology · 2025-01-20 · 8 citations

  articleOpen access

  Dimeric IgA (dIgA) is the dominant antibody in many mucosal tissues. It is actively transported onto mucosal surfaces as secretory IgA (sIgA) which plays an integral role in protection against enteric pathogens, particularly in young children. Therapeutic strategies that deliver engineered, potently neutralizing antibodies directly into the infant intestine through breast milk could provide enhanced antimicrobial protection for neonates. Here, we developed a murine model of maternal protective transfer against human rotavirus (RV) using systemic administration of a dimeric IgA monoclonal antibody (mAb). First, we showed that systemically administered dIgA passively transferred into breast milk and the stomach of suckling pups in a dose-dependent manner. Next, we optimized the recombinant production of a potently RV-neutralizing, VP4-specific dIgA (mAb41) antibody. We then demonstrated that systemic administration of dIgA and IgG mAb41 in lactating dams conferred protection from RV-induced diarrhea in suckling pups, with dIgA resulting in lower diarrhea incidence from IgG. Systemic delivery of engineered antimicrobial dIgA mAbs should be considered as an effective strategy for sIgA delivery to the infant gastrointestinal tract via breast milk to increase protection against enteric pathogens.

  PublisherDOI

• Acquisition of quaternary trimer interaction as a key step in the lineage maturation of a broad and potent HIV-1 neutralizing antibody

  Structure · 2025-05-23 · 1 citations

  article
  PublisherDOI

• An engineered immunogen activates diverse HIV broadly neutralizing antibody precursors and promotes acquisition of improbable mutations

  Science Translational Medicine · 2025-01-08 · 5 citations

  article

  Elicitation of HIV broadly neutralizing antibodies (bnAbs) by vaccination first requires the activation of diverse precursors, followed by successive boosts that guide these responses to enhanced breadth through the acquisition of somatic mutations. Because HIV bnAbs contain mutations in their B cell receptors (BCRs) that are rarely generated during conventional B cell maturation, HIV vaccine immunogens must robustly engage and expand B cells with BCRs that contain these improbable mutations. Here, we engineered an immunogen that activates diverse precursors of an HIV V3-glycan bnAb and promotes their acquisition of a functionally critical improbable mutation. This immunogen was validated biochemically, structurally, and in three different humanized immunoglobulin mouse models that were designed to test HIV immunogens. These results provide a blueprint for rationally designing priming immunogens that explicitly target the elicitation of antibodies with functional yet improbable mutations.

  PublisherDOI

• Vaccine induction of heterologous HIV-1-neutralizing antibody B cell lineages in humans

  Cell · 2025-11-01

  articleOpen access
  PublisherDOI

• BPS2025 - Rational engineering of HIV-1 Env to enhance recognition of fusion peptide in a glycan-dependent manner

  Biophysical Journal · 2025-02-01

  articleSenior author
  PublisherDOI

• Structural determination of the HIV-1 Variable Region 3 epitope of antibody 19b

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-12-17

  articleOpen accessSenior authorCorresponding

  Summary The HIV-1 Envelope (Env) in its pre-receptor “closed” conformation is targeted by broadly neutralizing antibodies (bnAbs), while its receptor-bound “open” conformation, exposes immunodominant epitopes targeted by non-neutralizing antibodies. A human immunoglobin G (IgG) monoclonal antibody (mAb), 19b, binds an Env third variable (V3) loop epitope that is only exposed in the open Env conformation. Despite widespread use of 19b to detect the open Env conformation in immunoassays, its epitope has not yet been structurally defined. Here we determine crystal structures of ligand-free and V3 peptide-bound 19b Fab to visualize details of this interaction. 19b utilizes both its heavy and light chains to interact with the V3 loop. The 5-residue heavy chain complementarity-determining region (CDR H3) facilitates a hydrophobic pocket for V3 residues to associate with. 19b adopts a cradle binding mode with its CDRH1, CDRL2 and CDRL3 mediating interactions with V3 regions that flank the conserved GPGR/Q motif, without making substantial contacts with the GPGR arch region. Our high-resolution structures by elucidating the epitope, binding mode and the structural basis for the broad reactivity of 19b, fill a gap in our knowledge of a reagent that is widely used in immunoassays.

  PublisherDOI

• Isolation and characterization of IgG3 glycan-targeting antibodies with exceptional cross-reactivity for diverse viral families

  PLoS Pathogens · 2024-09-18 · 6 citations

  articleOpen access

  Broadly reactive antibodies that target sequence-diverse antigens are of interest for vaccine design and monoclonal antibody therapeutic development because they can protect against multiple strains of a virus and provide a barrier to evolution of escape mutants. Using LIBRA-seq (linking B cell receptor to antigen specificity through sequencing) data for the B cell repertoire of an individual chronically infected with human immunodeficiency virus type 1 (HIV-1), we identified a lineage of IgG3 antibodies predicted to bind to HIV-1 Envelope (Env) and influenza A Hemagglutinin (HA). Two lineage members, antibodies 2526 and 546, were confirmed to bind to a large panel of diverse antigens, including several strains of HIV-1 Env, influenza HA, coronavirus (CoV) spike, hepatitis C virus (HCV) E protein, Nipah virus (NiV) F protein, and Langya virus (LayV) F protein. We found that both antibodies bind to complex glycans on the antigenic surfaces. Antibody 2526 targets the stem region of influenza HA and the N-terminal domain (NTD) region of SARS-CoV-2 spike. A crystal structure of 2526 Fab bound to mannose revealed the presence of a glycan-binding pocket on the light chain. Antibody 2526 cross-reacted with antigens from multiple pathogens and displayed no signs of autoreactivity. These features distinguish antibody 2526 from previously described glycan-reactive antibodies. Further study of this antibody class may aid in the selection and engineering of broadly reactive antibody therapeutics and can inform the development of effective vaccines with exceptional breadth of pathogen coverage.

  PublisherDOI

Recent grants

• Structural characterization of Fab-dimerized glycan-reactive antibodies that neutralize HIV-1

  NIH · $3.4M · 2021–2026

• Effect of natural and engineered variations on structure and biophysics of SARS-CoV-2 spike

  NIH · $3.8M · 2022–2027

• Structure and dynamics of a functional cavity in the HIV-1 Envelope, and its role in conformational changes required for infection

  NIH · $428k · 2020–2022

• Structural definition of CD4-induced HIV-1 Env conformational changes required for infection

  NIH · $6.1M · 2019–2030

Frequent coauthors

• Peter D. Kwong

  National Institutes of Health

  234 shared

• Barton F. Haynes

  Duke University

  129 shared

• Kevin O. Saunders

  Duke University

  103 shared

• John R. Mascola

  98 shared

• Katarzyna Janowska

  Duke University

  78 shared

• Rory Henderson

  Duke University

  78 shared

• Robert J. Edwards

  Duke University

  77 shared

• Carole A. Bewley

  National Institutes of Health

  76 shared

Labs

• Acharya LabPI

Education

• Ph.D., Biochemistry

  University of California, Berkeley

  1995

• B.S., Chemistry

  University of California, Berkeley

  1989