About

Neil King is an Assistant Professor of Biochemistry at the University of Washington. His research focuses on proteins, which are nature’s building blocks for constructing molecular machines. His group aims to incorporate the stable yet dynamic features of proteins into the design of functional protein-based nanomaterials. The goal of this research is to create new opportunities for the treatment and prevention of disease. To achieve this, he employs computational protein design along with a variety of biochemical, biophysical, and structural techniques to produce and characterize novel materials.

Research topics

• Biology
• Virology
• Immunology
• Genetics
• Medicine
• Computational biology
• Computer Science
• Artificial Intelligence
• Cell biology
• Chemistry
• Biochemistry
• Materials science
• Internal medicine
• Biophysics
• Nanotechnology
• Environmental health

Selected publications

• Improving the immunogenicity of <i>E. coli</i> FimH via multivalent display on I53-50 nanoparticles

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-03-09

  articleOpen accessSenior author

  Abstract Urinary tract infections, caused primarily by uropathogenic E. coli , are a significant public health burden, affecting approximately 50% of women worldwide. The adhesin FimH is responsible for host receptor binding and is therefore a promising vaccine candidate, but prior studies showed that recombinant monomeric FimH is poorly immunogenic. Here we displayed FimH antigens on the two-component protein nanoparticle I53-50 to generate nanoparticle immunogens that elicit robust levels of receptor-blocking antibodies in mice and non-human primates. We produced nanoparticle immunogens displaying either the FimH lectin domain or a recently reported conformationally stabilized antigen, FimH-DSG, comprising both the lectin and pilin domains. When formulated on aluminum hydroxide, both nanoparticle immunogens elicited similar levels of receptor-blocking activity as a ten-fold higher dose of monomeric FimH-DSG formulated with a potent adjuvant. The improved manufacturability of the stabilized antigen, combined with the ability of nanoparticle display to obviate the need for complex adjuvants, provides important preclinical data for FimH-based vaccines intended to prevent urinary tract infections. More broadly, our data extend the applicability of the I53-50 nanoparticle platform, which to date has been mainly used for displaying viral and protozoan antigens, to bacterial indications.

  PublisherOA PDFDOI

• A stabilized tandem antigen chimera that elicits potent malaria transmission-reducing activity

  Nature Communications · 2026-01-24

  articleOpen access

  Malaria parasite transmission remains a barrier to elimination since asymptomatic individuals sustain the infectious reservoir. Transmission-blocking vaccine (TBV) candidates targeting Plasmodium falciparum (Pf) gametocyte surface proteins Pfs230 and Pfs48/45 have shown promise in clinical trials. Several vaccine candidates have been developed for these antigens, yet it is unclear which elicit the most robust and durable transmission-blocking responses. From structure-function relationships of monoclonal antibodies in complex with both antigens, we report the development of a stabilized tandem antigen chimera (STAC), which presents the most potent epitopes from Pfs230 domain 1 (Pfs230-D1) and Pfs48/45 domain 3 (Pfs48/45-D3) in a single construct, while masking non-functional epitopes using an engineered pseudo-native domain disposition. Iterative structure-guided optimization improved antigen yields and stability, while nanoparticle-based multimerization enhanced the functional transmission-reducing activity elicited by the immunogen in female mice. Immunizations with STAC genetically conjugated to self-assembling protein nanoparticles elicited antibodies with potent transmission-reducing activity comparable or superior to the multimerized Pfs230-D1 and Pfs48/45-D3. These findings establish STAC as a promising next-generation TBV candidate to disrupt malaria transmission and accelerate elimination efforts. More broadly, our results support the engineering of highly ordered and stable multi-domain antigens in a single protein as a strategy for the cost-efficient development of multi-component vaccines.

  PublisherOA PDFDOI

• Membrane protein solubilization and structure determination using de novo-designed amphipathic proteins

  Open MIND · 2026-02-11

  other

  WRAPs (Water-soluble RFdiffused Amphipathic Proteins) are genetically encoded de novo proteins that surround the lipid-interacting hydrophobic surfaces of transmembrane proteins, rendering them thermostable and water-soluble without the need for detergents. This repo includes scripts and inputs to generate WRAPs as described in https://www.biorxiv.org/content/10.1101/2025.02.04.636539v1.

  DOI

• Membrane protein solubilization and structure determination using de novo-designed amphipathic proteins

  Zenodo (CERN European Organization for Nuclear Research) · 2026-01-31

  otherOpen access

  WRAPs (Water-soluble RFdiffused Amphipathic Proteins) are genetically encoded de novo proteins that surround the lipid-interacting hydrophobic surfaces of transmembrane proteins, rendering them thermostable and water-soluble without the need for detergents. This repo includes scripts and inputs to generate WRAPs as described in https://www.biorxiv.org/content/10.1101/2025.02.04.636539v1.

  PublisherDOI

• Mannosylated nanoparticle immunogens enhance the circumsporozoite protein-specific B cell response and improve protection against sporozoite challenge

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-05-07

  articleOpen accessSenior authorCorresponding

  Underprocessed oligomannose glycans on protein nanoparticle immunogens engage the innate immune system through mannose-binding lectin and complement, enhancing immunogen trafficking and B cell responses. However, the extent to which oligomannose glycans directly improve protective immunity has remained unclear. Here we generate a series of CSP-bearing I53-50 nanoparticle malaria vaccine candidates with defined numbers and types of engineered N-linked glycans and systematically evaluate their immunogenicity and protective efficacy. Oligomannose display enhanced early plasmablast and germinal center B cell responses, leading to increased CSP-specific memory B cells, long-lived plasma cells, and durable serum antibody titers. Furthermore, nanoparticles bearing oligomannose glycans conferred the strongest protection against sporozoite challenge. By comparing immunogens with defined glycoforms, we attribute improved immune responses and protection specifically to oligomannose rather than complex or truncated glycans. These results will help guide the development of general strategies for glycan engineering aimed at enhancing the protective efficacy of nanoparticle vaccines.

  PublisherDOI

• Stabilization of the H5 clade 2.3.4.4b hemagglutinin improves vaccine-elicited neutralizing antibody responses in mice

  Science Translational Medicine · 2026-03-04

  articleOpen accessSenior authorCorresponding

  Transmission of highly pathogenic avian influenza from H5 clade 2.3.4.4b has expanded in recent years to infect large populations of birds and mammals, heightening the risk of a human pandemic. Influenza viruses that are adapted to transmission in birds and a variety of mammals tend to have a less stable hemagglutinin (HA) than seasonal influenza viruses, enabling membrane fusion at comparatively higher pH levels. Here, we combined five mutations in the H5 HA that increased its melting temperature and promoted stable closure of the HA trimer. Structural analysis by cryo-electron microscopy revealed that the stabilizing mutations create several new hydrophobic interactions while maintaining the local HA structure. We found that vaccinating mice with stabilized H5 HA immunogens resulted in higher hemagglutination inhibition and neutralization titers than nonstabilized comparators. Epitope mapping of vaccine-elicited polyclonal antibody responses using negative-stain electron microscopy and deep mutational scanning showed that site E on the side of the HA receptor binding domain was immunodominant across all groups; however, the stabilized immunogens shifted responses toward the receptor binding site, which elicited a higher proportion of neutralizing antibodies. Consistent with these findings, stabilized H5 HA immunogens delivered as messenger RNA-lipid nanoparticle (mRNA-LNP) vaccines protected mice against H5N1 challenge. These findings highlight that H5 HA-stabilizing mutations enhance the quality of antibody responses across different vaccine formats, underscoring their potential to improve pandemic preparedness vaccines targeting viruses from this widely circulating clade.

  PublisherOA PDFDOI

• Computational design of membrane fusion proteins

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-05-07

  articleOpen accessSenior author

  The fusion of two distinct biological membranes is an evolutionarily conserved process essential to cellular organization and physiology. Membrane fusion is driven by the refolding of fusogenic proteins into low-energy postfusion states that overcome the energetic barrier to bilayer merger. Here we report a computational method for the design of synthetic fusogens inspired by the architecture of the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex. Using machine learning-guided protein design to extensively remodel backbone geometry and sequence, we generated heterodimeric SNARE-like assemblies that efficiently catalyze cell-cell membrane fusion. These minimal two-component fusogens exhibit substantially higher fusion activity than native multisubunit SNARE complexes. Structural and functional analyses identify the key determinants required for fusogenic activity and reveal a modularity that enables control of fusion through chemically induced heterodimerization. In addition to cell-cell fusion, the synthetic fusogens drive fusion between endoplasmic reticulum and mitochondrial membranes from human cells, demonstrating their potential as tools for programmable manipulation of intracellular membranes. Together, these results establish a general framework for the rational design of synthetic fusogens and expand the toolkit for engineering membrane dynamics in living systems.

  PublisherDOI

• Multivalent Antigen Display on Nanoparticles Diversifies B Cell Responses

  Zenodo (CERN European Organization for Nuclear Research) · 2026-12-28

  articleOpen access

  Nanoparticles for multivalent display and delivery of vaccine antigens have emerged as a promising avenue for enhancing B cell responses to protein subunit vaccines. Here, we evaluated B cell responses in rhesus macaques immunized with prefusion stabilized Respiratory Syncytial Virus (RSV) F glycoprotein trimer compared to nanoparticles displaying 10 or 20 copies of the same antigen. We show that multivalent display skews antibody specificities and drives epitope-focusing of responding B cells. Antibody cloning and repertoire sequencing revealed that focusing was driven by expansion of clonally distinct B cells through recruitment of diverse precursors. We identified two antibody lineages that developed either ultrapotent neutralization or pneumovirus cross-neutralization from precursor B cells with low initial affinity for the RSV-F immunogen. This suggests that increased avidity by multivalent display facilitates the activation and recruitment of these cells. Diversification of the B cell response by multivalent nanoparticle immunogens has broad implications for vaccine design.

  PublisherDOI

• Structural convergence and water-mediated substrate mimicry enable broad neuraminidase inhibition by human antibodies

  Nature Communications · 2025-08-01 · 4 citations

  articleOpen access

  Influenza has been responsible for multiple global pandemics and seasonal epidemics and claimed millions of lives. The imminent threat of a panzootic outbreak of avian influenza H5N1 virus underscores the urgent need for pandemic preparedness and effective countermeasures, including monoclonal antibodies (mAbs). Here, we characterize human mAbs that target the highly conserved catalytic site of viral neuraminidase (NA), termed NCS mAbs, and the molecular basis of their broad specificity. Cross-reactive NA-specific B cells were isolated by using stabilized NA probes of non-circulating subtypes. We found that NCS mAbs recognized multiple NAs of influenza A as well as influenza B NAs and conferred prophylactic protections in mice against H1N1, H5N1, and influenza B viruses. Cryo-electron microscopy structures of two NCS mAbs revealed that they rely on structural mimicry of sialic acid, the substrate of NA, by coordinating not only amino acid side chains but also water molecules, enabling inhibition of NA activity across multiple influenza A and B viruses, including avian influenza clade 2.3.4.4b H5N1 viruses. Our results provide a molecular basis for the broad reactivity and inhibitory activity of NCS mAbs targeting the catalytic site of NA through substrate mimicry.

  PublisherOA PDFDOI

• Computationally designed mRNA-launched protein nanoparticle immunogens elicit protective antibody and T cell responses in mice

  Science Translational Medicine · 2025-10-15 · 12 citations

  articleOpen accessSenior authorCorresponding

  Messenger RNA (mRNA) vaccines and computationally designed protein nanoparticle vaccines were both clinically derisked and licensed for the first time during the coronavirus disease 2019 (COVID-19) pandemic. These vaccine modalities have complementary immunological benefits that provide strong motivation for their combination. Here, we demonstrate proof of concept for genetic delivery of computationally designed protein nanoparticle immunogens. Using severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as a model system, we genetically fused a stabilized variant of the Wuhan-Hu-1 spike protein receptor binding domain (RBD) to a protein nanoparticle we previously designed for optimal secretion from human cells. Upon secretion, the nanoparticle formed monodisperse and antigenically intact assemblies displaying 60 copies of the RBD in an immunogenic array. Compared with mRNA vaccines encoding membrane-anchored spike protein and a secreted RBD trimer, an mRNA vaccine encoding the RBD nanoparticle elicited 5- to 28-fold higher titers of neutralizing antibodies in mice. In addition, the "mRNA-launched" RBD nanoparticle vaccine induced higher frequencies of antigen-specific CD8 T cells than the same immunogen delivered as adjuvanted protein and protected mice from either Wuhan-Hu-1 or Omicron BA.5 challenge. These results establish that delivering computationally designed protein nanoparticle immunogens through mRNA can combine the benefits of both vaccine modalities. More broadly, our data highlight the utility of computational protein design in genetic vaccination strategies.

  PublisherOA PDFDOI

Frequent coauthors

• David Baker

  University of Washington

  95 shared

• David Veesler

  University of Washington

  88 shared

• Lauren Carter

  University of Washington

  50 shared

• Jesse D. Bloom

  Cape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa

  41 shared

• Rogier W. Sanders

  Cornell University

  40 shared

• Andrew B. Ward

  Scripps Research Institute

  38 shared

• Brooke Fiala

  University of Washington

  37 shared

• Paul Ellingworth

  36 shared

Education

• Ph.D, Biochemistry and Molecular Biology

  University of California, Los Angeles

  2010

• B.S., Biomedical Engineering

  Northwestern University

  2004