About

Melissa Murphy is a Distinguished Service Professor of Marketing at the Tepper School of Business. She is involved in the faculty and research activities of the school, contributing to the academic community through her expertise in marketing. Her role includes engaging in research, teaching, and thought leadership within the institution, supporting the school's strategic vision to lead at the intersection of business, technology, and analytics.

Research topics

• Virology
• Immunology
• Biology
• Medicine
• Genetics
• Computational biology
• Chemistry

Selected publications

• A Multivalent Pan-Ebolavirus Nanoparticle Vaccine Provides Protection in Rodents from Lethal Infection by Adapted Zaire and Sudan Viruses

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-02-01 · 4 citations

  preprintOpen access

  Abstract Both Zaire ebolavirus (EBOV) and Sudan ebolavirus (SUDV) are members of the family Filoviridae , first discovered in 1976 during outbreaks of hemorrhagic fever in northern Zaire and southern Sudan. Ebola virus disease outbreaks are major public health events because of their potential for human-to-human transmission with high case fatality rates. Filoviral surface glycoproteins (GPs) are known to be the primary targets of neutralizing antibodies for protection from disease, and are the relevant immunogens in the two approved EBOV vaccines. Here we describe the design, electron microscopy-based structural characterization, and efficacy testing of a series of icosahedral I53-50 nanoparticles displaying prefusion trimeric EBOV and SUDV GP antigens. Mice and guinea pigs vaccinated with either a cocktail of EBOV-GP-I53-50 plus SUDV-GP-I53-50 or mosaic EBOV / SUDV-GP-I53-50 nanoparticles were protected from death or severe clinical signs of disease and weight loss, respectively, when challenged with either mouse-adapted EBOV or guinea pig-adapted SUDV.

  PublisherDOI

• Su1733 ORAL IL-23R ANTAGONIST MINIPROTEIN MB1 IS AS EFFECTIVE AS GUSELKUMAB IN A PRECLINICAL MODEL OF COLITIS

  Gastroenterology · 2024-05-01

  article
  PublisherDOI

• Influence of crosslinker on aptamer immobilization and aptasensor sensing response for non-metallic surfaces

  Biosensors and Bioelectronics · 2024-11-12 · 12 citations

  article
  PublisherDOI

• Deep mutational scanning reveals functional constraints and antibody-escape potential of Lassa virus glycoprotein complex

  Immunity · 2024-07-15 · 24 citations

  articleOpen access

  Lassa virus is estimated to cause thousands of human deaths per year, primarily due to spillovers from its natural host, Mastomys rodents. Efforts to create vaccines and antibody therapeutics must account for the evolutionary variability of the Lassa virus's glycoprotein complex (GPC), which mediates viral entry into cells and is the target of neutralizing antibodies. To map the evolutionary space accessible to GPC, we used pseudovirus deep mutational scanning to measure how nearly all GPC amino-acid mutations affected cell entry and antibody neutralization. Our experiments defined functional constraints throughout GPC. We quantified how GPC mutations affected neutralization with a panel of monoclonal antibodies. All antibodies tested were escaped by mutations that existed among natural Lassa virus lineages. Overall, our work describes a biosafety-level-2 method to elucidate the mutational space accessible to GPC and shows how prospective characterization of antigenic variation could aid the design of therapeutics and vaccines.

  PublisherOA PDFDOI

• Deep mutational scanning reveals functional constraints and antigenic variability of Lassa virus glycoprotein complex

  bioRxiv (Cold Spring Harbor Laboratory) · 2024-02-06 · 1 citations

  preprintOpen access

  Abstract Lassa virus is estimated to cause thousands of human deaths per year, primarily due to spillovers from its natural host, Mastomys rodents. Efforts to create vaccines and antibody therapeutics must account for the evolutionary variability of Lassa virus’s glycoprotein complex (GPC), which mediates viral entry into cells and is the target of neutralizing antibodies. To map the evolutionary space accessible to GPC, we use pseudovirus deep mutational scanning to measure how nearly all GPC amino-acid mutations affect cell entry and antibody neutralization. Our experiments define functional constraints throughout GPC. We quantify how GPC mutations affect neutralization by a panel of monoclonal antibodies and show that all antibodies are escaped by mutations that exist among natural Lassa virus lineages. Overall, our work describes a biosafety-level-2 method to elucidate the mutational space accessible to GPC and shows how prospective characterization of antigenic variation could aid design of therapeutics and vaccines.

  PublisherOA PDFDOI

• Influence of Crosslinker Functionality on Sensing Response and Immobilization Density of Aptamers on Non-Metallic Sensing Surfaces

  SSRN Electronic Journal · 2024-01-01

  preprintOpen access
  PublisherDOI

• Preclinical proof of principle for orally delivered Th17 antagonist miniproteins

  Cell · 2024-06-26 · 73 citations

  articleOpen access

  Interleukin (IL)-23 and IL-17 are well-validated therapeutic targets in autoinflammatory diseases. Antibodies targeting IL-23 and IL-17 have shown clinical efficacy but are limited by high costs, safety risks, lack of sustained efficacy, and poor patient convenience as they require parenteral administration. Here, we present designed miniproteins inhibiting IL-23R and IL-17 with antibody-like, low picomolar affinities at a fraction of the molecular size. The minibinders potently block cell signaling in vitro and are extremely stable, enabling oral administration and low-cost manufacturing. The orally administered IL-23R minibinder shows efficacy better than a clinical anti-IL-23 antibody in mouse colitis and has a favorable pharmacokinetics (PK) and biodistribution profile in rats. This work demonstrates that orally administered de novo-designed minibinders can reach a therapeutic target past the gut epithelial barrier. With high potency, gut stability, and straightforward manufacturability, de novo-designed minibinders are a promising modality for oral biologics.

  PublisherOA PDFDOI

• Allogenic Vertebral Body Adherent Mesenchymal Stromal Cells Promote Muscle Recovery in Diabetic Mouse Model of Limb Ischemia

  Annals of Vascular Surgery · 2024-09-27 · 1 citations

  articleOpen access

  BACKGROUND: Chronic limb-threatening ischemia (CLTI) carries a significant risk for amputation, especially in diabetic patients with poor options for revascularization. Phase I trials have demonstrated efficacy of allogeneic mesenchymal stromal cells (MSC) in treating diabetic CLTI. Vertebral bone-adherent mesenchymal stromal cells (vBA-MSC) are derived from vertebral bodies of deceased organ donors, which offer the distinct advantage of providing a 1,000x greater yield compared to that of living donor bone aspiration. This study describes the effects of intramuscular injection of allogenic vBA-MSC in promoting limb perfusion and muscle recovery in a diabetic CLTI mouse model. METHODS: A CLTI mouse model was created through unilateral ligation of the femoral artery in male polygenic diabetic TALLYHO mice. The treated mice were injected with vBA-MSC into the gracilis muscle of the ischemic limb 7 days post ligation. Gastrocnemius or tibialis muscle was assessed postmortem for fibrosis by collagen staining, capillary density via immunohistochemistry, and mRNA by quantitative real-time polymerase chain reaction (PCR). Laser Doppler perfusion imaging and plantar flexion muscle testing (MT) were performed to quantify changes in limb perfusion and muscle function. RESULTS: Compared to vehicle (Veh) control, treated mice demonstrated indicators of muscle recovery, including decreased fibrosis, increased perfusion, muscle torque, and angiogenesis. PCR analysis of muscle obtained 7 and 30 days post vBA-MSC injection showed an upregulation in the expression of MyoD1 (P = 0.03) and MyH3 (P = 0.008) mRNA, representing muscle regeneration, vascular endothelial growth factor A (VEGF-A) (P = 0.002; P = 0.004) signifying angiogenesis as well as interleukin (IL-10) (P < 0.001), T regulatory cell marker Foxp3 (P = 0.04), and M2-biased macrophage marker Mrc1 (CD206) (P = 0.02). CONCLUSIONS: These findings indicate human allogeneic vBA-MSC ameliorate ischemic muscle damage and rescue muscle function. These results in a murine model will enable further studies to develop potential therapies for diabetic CLTI patients.

  PublisherOA PDFDOI

• Potent neutralization of SARS-CoV-2 variants by RBD nanoparticle and prefusion-stabilized spike immunogens

  npj Vaccines · 2024-10-08 · 12 citations

  articleOpen access

  Abstract We previously described a two-component protein nanoparticle vaccine platform that displays 60 copies of the SARS-CoV-2 spike protein RBD (RBD-NP). The vaccine, when adjuvanted with AS03, was shown to elicit robust neutralizing antibody and CD4 T cell responses in Phase I/II clinical trials, met its primary co-endpoints in a Phase III trial, and has been licensed by multiple regulatory authorities under the brand name SKYCovione TM . Here we characterize the biophysical properties, stability, antigenicity, and immunogenicity of RBD-NP immunogens incorporating mutations from the B.1.351 (β) and P.1 (γ) variants of concern (VOCs) that emerged in 2020. We also show that the RBD-NP platform can be adapted to the Omicron strains BA.5 and XBB.1.5. We compare β and γ variant and E484K point mutant nanoparticle immunogens to the nanoparticle displaying the Wu-1 RBD, as well as to soluble prefusion-stabilized (HexaPro) spike trimers harboring VOC-derived mutations. We find the properties of immunogens based on different SARS-CoV-2 variants can differ substantially, which could affect the viability of variant vaccine development. Introducing stabilizing mutations in the linoleic acid binding site of the RBD-NPs resulted in increased physical stability compared to versions lacking the stabilizing mutations without deleteriously affecting immunogenicity. The RBD-NP immunogens and HexaPro trimers, as well as combinations of VOC-based immunogens, elicited comparable levels of neutralizing antibodies against distinct VOCs. Our results demonstrate that RBD-NP-based vaccines can elicit neutralizing antibody responses against SARS-CoV-2 variants and can be rapidly designed and stabilized, demonstrating the potential of two-component RBD-NPs as a platform for the development of broadly protective coronavirus vaccines.

  PublisherOA PDFDOI

• Antigen spacing on protein nanoparticles influences antibody responses to vaccination

  bioRxiv (Cold Spring Harbor Laboratory) · 2023-05-24 · 3 citations

  preprintOpen access

  SUMMARY Immunogen design approaches aim to control the specificity and quality of antibody responses to enable the creation of next-generation vaccines with improved potency and breadth. However, our understanding of the relationship between immunogen structure and immunogenicity is limited. Here we use computational protein design to generate a self-assembling nanoparticle vaccine platform based on the head domain of influenza hemagglutinin (HA) that enables precise control of antigen conformation, flexibility, and spacing on the nanoparticle exterior. Domain-based HA head antigens were presented either as monomers or in a native-like closed trimeric conformation that prevents exposure of trimer interface epitopes. These antigens were connected to the underlying nanoparticle by a rigid linker that was modularly extended to precisely control antigen spacing. We found that nanoparticle immunogens with decreased spacing between closed trimeric head antigens elicited antibodies with improved hemagglutination inhibition (HAI) and neutralization potency as well as binding breadth across diverse HAs within a subtype. Our “trihead” nanoparticle immunogen platform thus enables new insights into anti-HA immunity, establishes antigen spacing as an important parameter in structure-based vaccine design, and embodies several design features that could be used to generate next-generation vaccines against influenza and other viruses. HIGHLIGHTS Computational design of a closed trimeric HA head (“trihead”) antigen platform. Design of a rigid, extendable linker between displayed antigen and underlying protein nanoparticle enables precise variation of antigen spacing. Decreased antigen spacing of triheads elicits antibodies with the highest HAI, neutralizing activity, and cross-reactivity. Changes to antigen spacing alter epitope specificities of vaccine-elicited antibodies.

  PublisherOA PDFDOI

Frequent coauthors

• Neil P. King

  University of Washington

  30 shared

• Lauren Carter

  University of Washington

  24 shared

• Jesse D. Bloom

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

  22 shared

• David Veesler

  University of Washington

  21 shared

• Deleah Pettie

  Duke University

  21 shared

• Katharine H. D. Crawford

  University of Washington

  15 shared

• Claire Sydeman

  University of Washington

  14 shared

• Metin Sitti

  13 shared

Education

• Masters of Science, Biochemistry

  Western Washington University

  2012