Keersten M. Ricks

United States Army Medical Research Institute of Infectious Diseases

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Jay W. Hooper

United States Army Medical Research Institute of Infectious Diseases

Charles J. Shoemaker

United States Army Medical Research Institute of Infectious Diseases

Tamara L. Clements

United States Army Medical Research Institute of Infectious Diseases

Randal J. Schoepp

United States Army Medical Research Institute of Infectious Diseases

Jeffrey W. Koehler

United States Army Medical Research Institute of Infectious Diseases

Paul A. Kuehnert

United States Army Medical Research Institute of Infectious Diseases

Xiankun Zeng

United States Army Medical Research Institute of Infectious Diseases

Alexandra Jay

United States Army Medical Research Institute of Infectious Diseases

Franco Rossi

United States Army Medical Research Institute of Infectious Diseases

Jeffrey M. Smith

The University of Texas Medical Branch at Galveston

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United States Army Medical Research Institute of Infectious Diseases

156

Walter Reed Army Institute of Research

United States Department of the Army

National Institutes of Health

Henry M. Jackson Foundation

National Institute of Allergy and Infectious Diseases

University Hospital of Geneva

Vanderbilt University

United States Army Medical Research and Development Command

University of California, Davis

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Virus-Like Particles and Magnetic Microspheres Provide a Flexible and Sustainable Multiplexed Alphavirus Immunodiagnostic Platform

bioRxiv (Cold Spring Harbor Laboratory) (2018)

Keersten M. Ricks Charles J. Shoemaker Lesley C. Dupuy Olivier Flusin Matthew A. Voorhees

Abstract There is a pressing need for sustainable and sensitive immunodiagnostics for use in public health efforts to understand and combat the threat of endemic and emerging infectious diseases. We describe a novel approach to immunodiagnostics based on virus-like particles (VLPs) attached to magnetic beads. This flexible, innovative immunoassay system, based on the MAGPIX® platform, improves sensitivity by up to 2-logs and has faster sample-to-answer time over traditional methods. As a proof of concept, a retroviral-based VLP, that presents the Venezuelan equine encephalitis virus E1/E2 glycoprotein antigen on its surface, was generated and coupled to magnetic beads to create VLP-conjugated microspheres (VCMs). Using these VCMs, IgG and IgM antibodies were detectable in nonhuman primate (NHP) and human clinical serum samples at dilutions of 1 × 10 4 and greater. We extended the VCM methodology to two other New-World alphaviruses, eastern and western equine encephalitis viruses, as well as an Old-World alphavirus, Chikungunya virus, demonstrating the flexibility of this approach toward different VLP architectures. When multiplexed on the MAGPIX® platform, the VCMs provided differential diagnosis between Old-World and New-World alphaviruses and well as a route toward assessing the humoral response to both natural infection and vaccination. This VCM system will allow more rapid and efficient detection of endemic and emerging viral pathogens in human populations.

10.1101/335315

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A SARS-CoV-2 Spike Ferritin Nanoparticle Vaccine Is Protective and Promotes a Strong Immunological Response in the Cynomolgus Macaque Coronavirus Disease 2019 (COVID-19) Model

Vaccines (2022)

Sara C. Johnston Keersten M. Ricks Inès Lakhal-Naouar Alexandra Jay Caroline Subra

The COVID-19 pandemic has had a staggering impact on social, economic, and public health systems worldwide. Vaccine development and mobilization against SARS-CoV-2 (the etiologic agent of COVID-19) has been rapid. However, novel strategies are still necessary to slow the pandemic, and this includes new approaches to vaccine development and/or delivery that will improve vaccination compliance and demonstrate efficacy against emerging variants. Here, we report on the immunogenicity and efficacy of a SARS-CoV-2 vaccine comprising stabilized, pre-fusion spike protein trimers displayed on a ferritin nanoparticle (SpFN) adjuvanted with either conventional aluminum hydroxide or the Army Liposomal Formulation QS-21 (ALFQ) in a cynomolgus macaque COVID-19 model. Vaccination resulted in robust cell-mediated and humoral responses and a significant reduction in lung lesions following SARS-CoV-2 infection. The strength of the immune response suggests that dose sparing through reduced or single dosing in primates may be possible with this vaccine. Overall, the data support further evaluation of SpFN as a SARS-CoV-2 protein-based vaccine candidate with attention to fractional dosing and schedule optimization.

Pandemic

Coronavirus

Vaccine efficacy

10.3390/vaccines10050717

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Citations (23)

Antibody Response to SARS-CoV-2 Infection and Vaccination in COVID-19-naïve and Experienced Individuals

Viruses (2022)

Susan L. Uprichard Amornrat O’Brien Monika Evdokimova Cynthia L. Rowe Cara Joyce

Understanding the magnitude of responses to vaccination during the ongoing SARS-CoV-2 pandemic is essential for ultimate mitigation of the disease. Here, we describe a cohort of 102 subjects (70 COVID-19-naïve, 32 COVID-19-experienced) who received two doses of one of the mRNA vaccines (BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna)). We document that a single exposure to antigen via infection or vaccination induces a variable antibody response which is affected by age, gender, race, and co-morbidities. In response to a second antigen dose, both COVID-19-naïve and experienced subjects exhibited elevated levels of anti-spike and SARS-CoV-2 neutralizing activity; however, COVID-19-experienced individuals achieved higher antibody levels and neutralization activity as a group. The COVID-19-experienced subjects exhibited no significant increase in antibody or neutralization titer in response to the second vaccine dose (i.e., third antigen exposure). Finally, we found that COVID-19-naïve individuals who received the Moderna vaccine exhibited a more robust boost response to the second vaccine dose (p = 0.004) as compared to the response to Pfizer-BioNTech. Ongoing studies with this cohort will continue to contribute to our understanding of the range and durability of responses to SARS-CoV-2 mRNA vaccines.

2019-20 coronavirus outbreak

Betacoronavirus

Antibody response

Sars virus

Convalescent plasma

Coronavirus Infections

10.3390/v14020370

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Humoral immunogenicity of a Coronavirus Disease 2019 (COVID-19) DNA Vaccine in Rhesus Macaques (Macaca mulatta) Delivered using Needle-free Jet Injection

bioRxiv (Cold Spring Harbor Laboratory) (2022)

Alexandra Jay Steven A. Kwilas Matthew Josleyn Keersten M. Ricks Jay W. Hooper

Abstract A SARS-CoV-2 DNA vaccine targeting the spike protein and delivered by jet injection, nCOV-S(JET), previously shown to protect wild-type and immunosuppressed Syrian hamsters ( Mesocricetus auratus ), was evaluated via two needle-free delivery methods in rhesus macaques ( Macaca mulatta ). The methods included intramuscular delivery of 2 mg per vaccination with the PharmaJet Stratis device and intradermal delivery of 0.4 mg per vaccination with the PharmaJet Tropis device. We hypothesized that the nCOV-S(JET) vaccine would mount detectable neutralizing antibody responses when delivered by needle-free jet injection by either the intradermal or intramuscular route. When delivered intramuscularly, the vaccines elicited neutralizing and variant (Beta, Gamma, and Delta) cross-neutralizing antibodies against SARS-CoV-2 in all six animals after three vaccinations. When delivered at a lower dose by the intradermal route, strong neutralizing antibody responses were only detected in two of six animals. This study confirms that a vaccine previously shown to protect in a hamster model can elicit neutralizing and cross-neutralizing antibodies against SARS-CoV-2 in nonhuman primates. We posit that nCOV-S(JET) has the potential for use as booster vaccine in heterologous vaccination strategies against COVID-19.

Mesocricetus

Rhesus macaque

Intramuscular injection

10.1101/2022.09.12.507647

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Direct transfer of HRPII-magnetic bead complexes to malaria rapid diagnostic tests significantly improves test sensitivity

Malaria Journal (2016)

Keersten M. Ricks Nicholas M. Adams Thomas Scherr Frederick R. Haselton David W. Wright

The characteristic ease of use, rapid time to result, and low cost of malaria rapid diagnostic tests (RDTs) promote their widespread use at the point-of-care for malaria detection and surveillance. However, in many settings, the success of malaria elimination campaigns depends on point-of-care diagnostics with greater sensitivity than currently available RDTs. To address this need, a sample preparation method was developed to deliver more biomarkers onto a malaria RDT by concentrating the biomarker from blood sample volumes that are too large to be directly applied to a lateral flow strip.In this design, Ni-NTA-functionalized magnetic beads captured the Plasmodium falciparum biomarker HRPII from a P. falciparum D6 culture spiked blood sample. This transfer of magnetic beads to the RDT was facilitated by an inexpensive 3D-printed apparatus that aligned the sample tube with the sample deposition pad and a magnet beneath the RDT. Biomarkers were released from the bead surface onto the lateral flow strip using imidazole-spiked running buffer. Kinetics of HRPII binding to the Ni-NTA beads as a function of blood sample volume were explored prior to determining the effect of the proposed method on the limit of detection of Paracheck RDTs.More than 80 % of HRPII biomarkers were extracted from blood sample volumes ranging from 25 to 250 µL. The time required to reach 80 % binding ranged from 5 to 60 min, depending on sample volume. Using 250 μL of blood and a 30-min biomarker binding time, the limit of detection of the Paracheck Pf RDT brand was improved by 21-fold, resulting in a limit of detection below 1 parasite/μL.This approach has the sensitivity and simplicity required to assist in malaria elimination campaigns in settings with limited access to clinical and laboratory resources.

Magnetic bead

Point of care

Bead

Point-of-Care Testing

Sample Preparation

Sample (material)

10.1186/s12936-016-1448-6

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Citations (18)

Development of a specific MPXV antigen detection immunodiagnostic assay

Frontiers in Microbiology (2023)

Ian Davis Jackie M. Payne Victoria L. Olguin M. Sanders Tamara Clements

Human monkeypox (mpox) has recently become a global public health emergency; however, assays that detect mpox infection are not widely available, largely due to cross-reactivity within the Orthopoxvirus genus. Immunoassay development was largely confined to researchers who focus on biothreats and endemic areas (Central and West Africa) until the 2022 outbreak. As was noted in the COVID-19 pandemic, antigen detection assays, integrated with molecular assays, are necessary to help curb the spread of disease. Antigen-detecting immunoassays offer the advantage of providing results ranging from within min to h and in lateral flow formats; they can be deployed for point-of-care, home, or field use. This study reports the development of an mpox-specific antigen detection immunoassay developed on a multiplexed, magnetic-bead-based platform utilizing reagents from all research sectors (commercial, academic, and governmental). Two semi-quantitative assays were developed in parallel and standardized with infectious mpox virus (MPXV) cell culture fluid and MPXV-positive non-human primate (NHP) sera samples. These assays could detect viral antigens in serum, were highly specific toward MPXV as compared to other infectious orthopoxviruses (vaccinia virus, cowpox virus, and camelpox virus), and exhibited a correlation with quantitative PCR results from an NHP study. Access to a toolbox of assays for mpox detection will be key for identifying cases and ensuring proper treatment, as MPXV is currently a global traveler.

Monkeypox

Orthopoxvirus

Variola virus

10.3389/fmicb.2023.1243523

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Citations (13)

Development of a bead-based immunoassay using virus-like particles for detection of alphaviral humoral response

Journal of Virological Methods (2019)

Keersten M. Ricks Charles J. Shoemaker Lesley C. Dupuy Olivier Flusin Matthew A. Voorhees

Virus-like particle

10.1016/j.jviromet.2019.04.013

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Citations (12)

Development of a sustainable diagnostic toolbox for serosurveillance of West African infectious diseases

International Journal of Infectious Diseases (2019)

Keersten M. Ricks Jeffrey W. Koehler Charles J. Shoemaker M. Voorhees Randal J. Schoepp

Purpose: The spread of infectious disease continues to present a challenge for modern global public health initiatives, as was evidenced by the recent Ebola outbreak in West Africa. In order to understand emerging and re-emerging pathogens and risk of exposure, overseas laboratories need access to sustainable and reliable immunodiagnostic assays. Methods & Materials: We designed a multiplexed immunoassay centered on coupling recombinant proteins and/or virus-like particles to magnetic beads to detect IgM and IgG in a serum sample for EBOV, LASV, MARV, CCHFV, RVFV, alphaviruses, and flaviviruses. This flexible, immunoassay system, based on the MAGPIX® platform, improves sensitivity by up to 2-logs and has faster sample-to-answer time over traditional methods. Assays were developed and validated with animal models and human samples of known etiology. Nigerian human sera, through an acute febrile illness (AFI) study collaboration with the Joint West Africa Research Group (JWARG), were then screened with these assays to determine disease prevalence. Results: Greater than 50% IgG prevalence for alphaviruses and flaviviruses was observed, which is expected as it is known these families of viruses circulate in these regions. Less than 10% IgG prevalence rates were observed for MARV, EBOV, LASV, and RVFV. Notably, we observed greater than 50% CCHFV IgG prevalence rate in samples tested. Conclusion: Understanding the seroprevalence of emerging infectious diseases can give us a window into the risk of potential outbreaks. In the future, we will continue to screen AFI samples in Nigeria, Ghana, and Liberia in collaboration with JWARG. We also aim to extend surveillance to East African countries—Uganda and Kenya. Additionally, we hope to utilize these assays to screen acute sera for IgM and antigen prevalence. By developing a sustainable diagnostic program and transitioning these capabilities to our in-country collaborators, we have the best chance at rapidly responding to emerging infectious diseases and ultimately avoiding another widespread outbreak.

Seroprevalence

Emerging infectious disease

Lassa fever

10.1016/j.ijid.2018.11.074

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Citations (1)

Application of a Machine Learning-Based Classification Approach for Developing Host Protein Diagnostic Models for Infectious Disease

Diagnostics (2024)

Thomas Scherr Christina E. Douglas Kurt E. Schaecher Randal J. Schoepp Keersten M. Ricks

In recent years, infectious disease diagnosis has increasingly turned to host-centered approaches as a complement to pathogen-directed ones. The former, however, typically requires the interpretation of complex multiple biomarker datasets to arrive at an informative diagnostic outcome. This report describes a machine learning (ML)-based classification workflow that is intended as a template for researchers seeking to apply ML approaches for developing host-based infectious disease biomarker classifiers. As an example, we built a classification model that could accurately distinguish between three disease etiology classes: bacterial, viral, and normal in human sera using host protein biomarkers of known diagnostic utility. After collecting protein data from known disease samples, we trained a series of increasingly complex Auto-ML models until arriving at an optimized classifier that could differentiate viral, bacterial, and non-disease samples. Even when limited to a relatively small training set size, the model had robust diagnostic characteristics and performed well when faced with a blinded sample set. We present here a flexible approach for applying an Auto-ML-based workflow for the identification of host biomarker classifiers with diagnostic utility for infectious disease, and which can readily be adapted for multiple biomarker classes and disease states.

Biomarker Discovery

10.3390/diagnostics14121290

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Seroepidemiologic Survey of Crimean-Congo Hemorrhagic Fever Virus in Logging Communities, Myanmar

Emerging infectious diseases (2021)

Tierra Smiley Evans Theingi Win Myat Nang Sarm Hom Keersten M. Ricks Min Thein Maw

Abstract Crimean-Congo hemorrhagic fever virus (CCHFV) is endemic in Asia, infecting many animal hosts, but CCHFV has not been reported in Myanmar. We conducted a seroepidemiologic survey of logging communities in Myanmar and found CCHFV exposure was common (9.8%) and exposure to wild animal blood and body fluids was associated with seropositivity.

Crimean–Congo hemorrhagic fever

10.3201/eid2706.203223

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Citations (7)