About

Paul F. Bates, PhD, is a Professor of Microbiology at the University of Pennsylvania's Perelman School of Medicine. His research focuses on the interactions between viruses and their host cells, utilizing molecular, cell biological, and genetic tools to understand how viruses invade host cells and evade host defenses. His laboratory has a particular emphasis on emerging viral pathogens, including filoviruses such as ebolavirus and Marburgvirus, and bunyaviruses like Hantaan, Andes, Sin Nombre, and La Crosse viruses. Dr. Bates's work investigates viral glycoproteins and host factors that facilitate infection, with recent projects exploring the role of the innate antiviral factor Tetherin, which is capable of activating NFkB and acting as a broad-spectrum antiviral. His lab has developed innovative technologies, such as a gene-trap lentiviral vector to identify host genes involved in viral infection, and is actively studying how ebolavirus glycoproteins interact with cellular factors, including mechanisms of surface protein down-modulation and immune evasion. His research aims to uncover new therapeutic and prophylactic strategies against viral infections, contributing significantly to the understanding of viral entry, immune evasion, and host-virus interactions.

Research topics

• Virology
• Immunology
• Biology
• Genetics
• Medicine
• Biochemistry

Selected publications

• Mutations that positively affect <i>Bandavirus</i> glycoprotein function on VSV vectored vaccines

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-04-16

  articleOpen accessSenior authorCorresponding

  Abstract Severe fever with thrombocytopenia syndrome virus (SFTSV) and Heartland virus (HRTV) are emerging tick-borne bandaviruses. They have high case fatality rates (10%), and no FDA-approved vaccines exist for disease prevention. SFTSV and HRTV are therefore identified as priority pathogens. A recombinant vesicular stomatitis virus (rVSV) vaccine, which replaces the original VSV glycoprotein with the SFTSV glycoproteins, shows early promise for SFTSV as it induces strong immune responses that are protective against lethal challenge. However, rVSV-SFTSV is highly attenuated in cell culture, which may be due to incompatibility between the assembly sites of SFTSV (the Golgi and ERGIC) and that of VSV (the plasma membrane). In this study, we identify a noncanonical COPI binding motif found in the cytoplasmic tail of SFTSV glycoproteins and demonstrate that an amino acid substitution in this motif (K1071A) inhibits binding to COPI. This mutation results in increased surface expression of SFTSV glycoproteins, improved incorporation onto VSV virions, and enhanced replication of rVSV-SFSTV in vitro. A mutation in a homologous site (K1074A) of HRTV has similar results, and rVSV-HRTV K1074A exhibits increased replication in vitro and in vivo . We show that vaccination with rVSV-HRTV K1074A results in improved induction of neutralizing antibody responses in immunocompetent C57BL/6 mice, and neutralizing antibodies elicited by vaccination are protective when administered to severely immunocompromised mice via passive transfer. Overall, our study identifies a mutation that improves the efficacy of the rVSV-SFTSV vaccine candidate and introduces the first vaccine candidate directly addressing HRTV infections. Importance Severe fever with thrombocytopenia syndrome virus (SFTSV) and Heartland bandavirus (HRTV) are emerging tick-borne viruses with high fatality rates. FDA-approved vaccines and antiviral drugs are unavailable but critically needed. We identify an important mutation in the SFTSV glycoprotein that disrupts a previously unreported COPI binding site. The mutation improves the efficacy of the previously described recombinant vesicular stomatitis virus vaccine candidate for SFTSV (rVSV-SFTSV). We also develop an rVSV-HRTV vaccine and show potent induction of neutralizing antibodies and protection from lethal challenge. This is the first study directly addressing the lack of vaccines specifically targeting HRTV.

  PublisherOA PDFDOI

• Comparison of Vaccine Platforms for Machupo Virus

  Vaccines · 2026-03-31

  articleOpen accessSenior authorCorresponding

  BACKGROUND/OBJECTIVES: Pathogenic mammarenaviruses cause severe hemorrhagic and neurologic disease in humans. Machupo virus (MACV), a New World (NW) mammarenavirus, causes Bolivian hemorrhagic fever in humans, and there are no approved vaccines. METHODS: Here, we describe and compare the immunogenicity of three vaccines expressing the MACV glycoprotein complex (GPC) in C57BL/6 mice: a recombinant vesicular stomatitis virus (rVSV) and two different lipid nanoparticle (LNP)-encapsulated nucleoside-modified mRNA (mRNA-LNP) vaccines. The first mRNA-LNP vaccine, designated MACV mRNA, expresses the full-length MACV GPC. The second mRNA-LNP vaccine, called MACV VLP mRNA, encodes MACV GPC with appended sequences that induce the budding of virus-like particles (VLPs) with MACV GPC on the surface. This is the first description of any mRNA-LNP vaccine for MACV and the first comparison of mRNA and rVSVs as vaccine candidates for MACV. RESULTS: We find that two doses of either MACV mRNA or MACV VLP mRNA are required for the induction of robust humoral and cellular immune responses including total MACV GPC IgG, neutralizing antibodies, cross-reactive antibodies that bind the related Junín virus GPC, and MACV-specific T-cell responses. To further investigate vaccination strategies for MACV, we also evaluated a heterologous prime-boost regimen involving the MACV mRNA vaccine coupled with the rVSV-based MACV vaccine. We find that the highest levels of MACV GPC-specific IgG and neutralizing titers were achieved when heterologous mRNA and rVSV prime-boost regimens were employed. CONCLUSIONS: These results elucidate differences in the immune response to different vaccine platforms for MACV and can inform future vaccine development for NW arenaviruses.

  PublisherOA PDFDOI

• Homologous and Heterologous Vaccination Regimens with mRNA and rVSV Platforms Induce Potent Immune Responses Against SFTSV Glycoprotein

  Viruses · 2025-08-08 · 7 citations

  articleOpen accessSenior authorCorresponding

  BACKGROUND: Severe fever with thrombocytopenia syndrome virus (SFTSV) is a highly pathogenic bunyavirus with a high case-fatality ratio for which there is no approved vaccine. Studies have assessed different vaccine technologies. However, few studies have yet assessed the immunogenicity of heterologous prime-boost regimens. METHODS: Here, we compare a lipid nanoparticle (LNP)-encapsulated nucleoside-modified mRNA-based vaccine encoding the SFTSV glycoproteins, Gn and Gc, to our recently described recombinant VSV SFTSV (rVSV-SFTSV) vaccine in single dose, homologous, and heterologous prime-boost regimens in mice. RESULTS: We show that all regimens protect from pathogenic SFTSV challenge and elicit strong long-lasting antibody responses. Furthermore, strong cellular immunity is elicited by mRNA-LNP immunizations and by heterologous immunization with an rVSV-SFTSV prime and mRNA-LNP boost. Cellular responses robustly polarized towards a type 1 response, characterized by high levels of IFNγ, TNFα, and IL-2. Immunization with mRNA led to a mixed type 1/type 2 immune response, as determined by antibody isotypes IgG1 and IgG2c. We found that homologous immunization leads to stronger antibody responses while heterologous immunization drives a slightly stronger cellular response. CONCLUSIONS: Taken together, the vaccine platforms described here represent strong vaccine candidates for further development.

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• Chimeric Vesicular Stomatitis Virus Bearing Western Equine Encephalitis Virus Envelope Proteins E2-E1 Is a Suitable Surrogate for Western Equine Encephalitis Virus in a Plaque Reduction Neutralization Test

  Viruses · 2025-07-31

  articleOpen access

  In December 2023, infections of western equine encephalitis virus (WEEV) within Argentina were reported to the World Health Organization (WHO). By April 2024, more than 250 human infections, 12 of which were fatal, and 2500 equine infections were identified in South America. Laboratory diagnosis and surveillance in affected countries were hindered by a lack of facilities equipped with BSL-3 laboratories, as confirmatory serodiagnosis for WEEV requires live virus in the plaque reduction neutralization test (PRNT). To expand serodiagnosis for WEEV in the Americas, we developed a virus chimera composed of vesicular stomatitis virus (VSV) engineered to display the E2-E1 glycoproteins of WEEV (VSV/WEEV) in place of the VSV glycoprotein (G). PRNT90 and IC90 values of parental WEEV and VSV/WEEV were analogous using sera collected from mice, horses, and chickens. VSV/WEEV rapidly formed plaques with clear borders and reduced the assay readout time by approximately 8 h compared to the parental virus. Overall, we demonstrate that chimeric VSV/WEEV is a suitable surrogate for WEEV in a diagnostic PRNT. Use of chimeric VSV/WEEV in place of authentic WEEV will dramatically expand testing capacity by enabling PRNTs to be performed at BSL-2 containment, while simultaneously decreasing the health risk to testing personnel.

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• Tailoring the adjuvanticity of lipid nanoparticles by PEG lipid ratio and phospholipid modifications

  Nature Nanotechnology · 2025-06-23 · 33 citations

  articleOpen access
  PublisherOA PDFDOI

• Modeling Heartland virus disease in mice and therapeutic intervention with 4′-fluorouridine

  Journal of Virology · 2024-03-21 · 13 citations

  articleOpen access

  Heartland virus (HRTV) is an emerging tick-borne bandavirus that causes a febrile illness of varying severity in humans, with cases reported in eastern and midwestern regions of the United States. No vaccines or approved therapies are available to prevent or treat HRTV disease. Here, we describe the genetic changes, natural history of disease, and pathogenesis of a mouse-adapted HRTV (MA-HRTV) that is uniformly lethal in 7- to 8-week-old AG129 mice at low challenge doses. We used this model to assess the efficacy of the ribonucleoside analog, 4'-fluorouridine (EIDD-2749), and showed that once-daily oral treatment with 3 mg/kg of drug, initiated after the onset of disease, protects mice against lethal MA-HRTV challenge and reduces viral loads in blood and tissues. Our findings provide insights into HRTV virulence and pathogenesis and support further development of EIDD-2749 as a therapeutic intervention for HRTV disease. IMPORTANCE: More than 60 cases of HRTV disease spanning 14 states have been reported to the United States Centers for Disease Control and Prevention. The expanding range of the Lone Star tick that transmits HRTV, the growing population of at-risk persons living in geographic areas where the tick is abundant, and the lack of antiviral treatments or vaccines raise significant public health concerns. Here, we report the development of a new small-animal model of lethal HRTV disease to gain insight into HRTV pathogenesis and the application of this model for the preclinical development of a promising new antiviral drug candidate, EIDD-2749. Our findings shed light on how the virus causes disease and support the continued development of EIDD-2749 as a therapeutic for severe cases of HRTV infection.

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• Immunologic Predictors of Vaccine Responsiveness in Patients With Lymphoma and Chronic Lymphocytic Leukemia

  The Journal of Infectious Diseases · 2024-03-01 · 4 citations

  articleOpen access

  Patients with B-cell lymphomas have altered cellular components of vaccine responses due to malignancy and therapy, and the optimal timing of vaccination relative to therapy remains unknown. SARS-CoV-2 vaccines created an opportunity for new insights in vaccine timing because patients were challenged with a novel antigen across multiple phases of treatment. We studied serologic mRNA vaccine response in retrospective and prospective cohorts with lymphoma and CLL, paired with clinical and research immune parameters. Reduced serologic response was observed more frequently during active therapies, but non-response was also common within observation and post-treatment groups. Total IgA and IgM correlated with successful vaccine response. In individuals treated with CART-19, non-response was associated with reduced B and T follicular helper cells. Predictors of vaccine response varied by disease and therapeutic group, and therefore further studies of immune health during and after cancer therapies are needed to allow individualized vaccine timing.

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• Cellugyrin (synaptogyrin-2) dependent pathways are used by bacterial cytolethal distending toxin and SARS-CoV-2 virus to gain cell entry

  Frontiers in Cellular and Infection Microbiology · 2024-04-18 · 2 citations

  articleOpen access

  Aggregatibacter actinomycetemcomitans cytolethal distending toxin (Cdt) is capable of intoxicating lymphocytes macrophages, mast cells and epithelial cells. Following Cdt binding to cholesterol, in the region of membrane lipid rafts, the CdtB and CdtC subunits are internalized and traffic to intracellular compartments. These events are dependent upon, cellugyrin, a critical component of synaptic like microvesicles (SLMV Cg+ ). Target cells, such as Jurkat cells, rendered unable to express cellugyrin are resistant to Cdt-induced toxicity. Similar to Cdt, SARS-CoV-2 entry into host cells is initiated by binding to cell surface receptors, ACE-2, also associated with cholesterol-rich lipid rafts; this association leads to fusion and/or endocytosis of viral and host cell membranes and intracellular trafficking. The similarity in internalization pathways for both Cdt and SARS-CoV-2 led us to consider the possibility that cellugyrin was a critical component in both processes. Cellugyrin deficient Calu-3 cells (Calu-3 Cg- ) were prepared using Lentiviral particles containing shRNA; these cells were resistant to infection by VSV/SARS-CoV-2-spike pseudotype virus and partially resistant to VSV/VSV-G pseudotype virus. Synthetic peptides representing various regions of the cellugyrin protein were prepared and assessed for their ability to bind to Cdt subunits using surface plasmon resonance. Cdt was capable of binding to a region designated the middle outer loop (MOL) which corresponds to a region extending into the cytoplasmic surface of the SLMV Cg+ . SARS-CoV-2 spike proteins were assessed for their ability to bind to cellugyrin peptides; SARS-CoV-2 full length spike protein preferentially binds to a region within the SLMV Cg+ lumen, designated intraluminal loop 1A. SARS-CoV-2-spike protein domain S1, which contains the receptor binding domains, binds to cellugyrin N-terminus which extends out from the cytoplasmic surface of SLMV. Binding specificity was further analyzed using cellugyrin scrambled peptide mutants. We propose that SLMV Cg+ represent a component of a common pathway that facilitates pathogen and/or pathogen-derived toxins to gain host cell entry.

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• Safety, Immunogenicity, and Efficacy of a Recombinant Vesicular Stomatitis Virus Vectored Vaccine Against Severe Fever with Thrombocytopenia Syndrome Virus and Heartland Bandavirus

  Vaccines · 2024-12-12 · 9 citations

  articleOpen accessSenior authorCorresponding

  Background: Severe fever with thrombocytopenia syndrome virus (SFTSV) is a recently emerged tickborne virus in east Asia with over 18,000 confirmed cases. With a high case fatality ratio, SFTSV has been designated a high priority pathogen by the WHO and the NIAID. Despite this, there are currently no approved therapies or vaccines to treat or prevent SFTS. Vesicular stomatitis virus (VSV) represents an FDA-approved vaccine platform that has been considered for numerous viruses due to its low sero-prevalence in humans, ease in genetic manipulation, and promiscuity in incorporating foreign glycoproteins into its virions. Methods: In this study, we developed a recombinant VSV (rVSV) expressing the SFTSV glycoproteins Gn/Gc (rVSV-SFTSV) and assessed its safety, immunogenicity, and efficacy in C57BL/6, Ifnar−/−, and AG129 mice. Results: We demonstrate that rVSV-SFTSV is safe when given to immunocompromised animals and is not neuropathogenic when injected intracranially into young immunocompetent mice. Immunization of wild type (C57BL/6) and Ifnar−/− mice with rVSV-SFTSV resulted in high levels of neutralizing antibodies and protection in a lethal SFTSV challenge model. Additionally, passive transfer of sera from immunized Ifnar−/− mice into naïve animals was protective when given pre- or post-exposure. Finally, we demonstrate that immunization with rVSV-SFTSV cross protects AG129 mice against challenge with the closely related Heartland bandavirus despite negligible neutralizing titers to the virus. Conclusions: Taken together, these data suggest that rVSV-SFTSV is a promising vaccine candidate for SFTSV and Heartland bandavirus with a favorable safety profile.

  PublisherOA PDFDOI

• Prior vaccination promotes early activation of memory T cells and enhances immune responses during SARS-CoV-2 breakthrough infection

  Nature Immunology · 2023-09-21 · 106 citations

  articleOpen access
  PublisherOA PDFDOI

Recent grants

• Development of vaccines targeting a tick-borne phlebovirus

  NIH · $3.0M · 2020–2026

• NIH Grant R01CA076256

  NIH · $1.3M · 2004

• NIH Grant R01AI043455

  NIH · $1.3M · 2005

• NIH Grant R21AI043455

  NIH · $187k · 1999

• A VSV vectored vaccine for emergent tick-born phleboviruses

  NIH · $446k · 2020–2023

Frequent coauthors

• E. John Wherry

  University of Pennsylvania

  71 shared

• Josephine R. Giles

  University of Pennsylvania

  40 shared

• Allison R. Greenplate

  Translational Therapeutics (United States)

  35 shared

• Amy E. Baxter

  California University of Pennsylvania

  33 shared

• Scott E. Hensley

  University of Pennsylvania

  32 shared

• Divij Mathew

  University of Pennsylvania

  32 shared

• Mark M. Painter

  University of Pennsylvania

  31 shared

• Rishi R. Goel

  Harvard University

  30 shared

Labs

• Bates LabPI

Education

• PhD, Biochemistry

  Michigan State University

  1985

• BS, Bichemistry

  Pennsylvania State University

  1979