Biology subjects

O'Donnell, K. L.

Publications and source records attributed to O'Donnell, K. L..

10 recordsLinked to original sources

bioRxiv2026

A Single-Dose Bundibugyo Virus Vaccine Protects Macaques Within 3 Days

Bundibugyo virus (BDBV), a member of the orthoebolaviruses in the Filoviridae family, causes severe hemorrhagic disease with high case-fatality rates. Currently, there are no medical countermeasures approved for human use hampering the response to the large ongoing outbreak in the Democratic Republic of the Congo and Uganda. While vesicular stomatitis virus (VSV)-based vaccines have demonstrated fast-acting prophylactic single-dose efficacy against multiple filoviruses, it has yet to be defined for VSV-BDBV. Here, we evaluated the rapid protection by a single-dose vaccination of VSV-BDBV in nonhuman primates (NHPs). Vaccination elicited rapid innate and early adaptive immune responses and conferred complete protection from clinical disease against BDBV challenge within 3 days. Vaccinated NHPs exhibited minimal clinical signs, limited systemic inflammation, and no infectious virus was isolated from the blood at any time. Protection correlated with neutralizing antibodies and Fc effector functionality of the humoral immune response. These findings establish VSV-BDBV as a fast-acting vaccine candidate suitable for outbreak response and highlight immune mechanisms underlying rapid protection.

microbiology↗

bioRxiv2026

Low-dose VSV-EBOV vaccination provides rapid protection from lethal Ebola virus challenge

In the decade since the West African Ebola virus (EBOV) epidemic, several medical countermeasures against this often-fatal hemorrhagic disease have been approved by regulatory authorities for human use. This includes monoclonal antibody-based therapies and vaccines which have been stockpiled in limited quantities. One of the vaccines is based on vesicular stomatitis virus (VSV) expressing the EBOV glycoprotein (GP) as the immunogen. The vaccine is stockpiled in limited quantity for emergency use. A single high dose has been shown to rapidly protect humans within 10 days. We developed an updated version of this vaccine expressing the GP from the 2015 EBOV-Makona isolate. Here, we wanted to determine the protective efficacy within 10 days of a single moderate dose (10-fold and 1,000-fold dilution) of the updated vaccine in nonhuman primates (NHPs). As a comparator we included a 1000-fold dilution dose group of the approved vaccine expressing the EBOV-Kikwit GP. While we achieved uniform protection with the approved vaccine at the moderate dose, only 50% of the NHPs receiving the same dose of the updated vaccine expressing the EBOV-Makona GP were protected. This study highlights the importance of evaluating VSV-based vaccine stocks expressing different filovirus GPs in preclinical models prior to progression with clinical development. Our study also highlights that rapid vaccination with reduced doses still leads to protection but at the cost of "sterile" immunity raising concerns regarding EBOV persistence and potential downstream transmission. Therefore, lower vaccine doses should only be considered in cases of severe vaccine shortage.

microbiology↗

bioRxiv2025

Acute malaria dysregulates specialized lymph node macrophages to suppress vaccine-elicited protection against Ebola virus

The filovirus, Ebola virus (EBOV), causes outbreaks of Ebola virus disease (EVD) throughout equatorial Africa. ERVEBO(R) (rVSV/EBOV) is a replication-competent, recombinant vesicular stomatitis virus (rVSV)-vectored vaccine licensed to control EVD outbreaks. EVD outbreaks occur in regions endemic for Plasmodium-caused malaria. Plasmodium infections persist due in part to the parasites ability to evade sterilizing immunity which also dampens immune responses to heterologous vaccines. Acute murine Plasmodium infection at the time of rVSV/EBOV vaccination reduced vaccine-mediated protection against mouse-adapted EBOV (ma-EBOV) challenge. Decreased protection was associated with a Plasmodium-induced interferon gamma (IFN-{gamma})-mediated decrease of rVSV/EBOV replication in lymph node (LN) macrophages, resulting in reduced primary anti-EBOV glycoprotein antibody responses. Higher doses of rVSV/EBOV partially overcame the antibody deficits and elicited protective responses. Evidence of the negative impact of Plasmodium on the efficacy of low dose rVSV/EBOV vaccine protocols supports the use of high antigen loads in effective management of EVD outbreaks. IMPORTANCEWe show that blood-stage murine Plasmodium infections negatively impacts the primary antibody response elicited by low dose rVSV/EBOV vaccination and results in reduced protection against a lethal dose of ma-EBOV. This defect occurs within the draining lymph node due to the elevation of IFN-{gamma} elicted in Py-infected mice. The Py-imposed decrease in vaccine-mediated protection can be overcome with higher doses of rVSV/EBOV. While the strong protection conferred by rVSV/EBOV and significant side effects known to be associated with this vaccine have led to the suggestion that the vaccine dosage be reduced19, our studies provide a rationale for maintaining a higher dose.

microbiology↗

bioRxiv2025

Single-dose VSV-Sudan virus vaccine protects from lethal Sudan virus infection within one week: a challenge study in macaques

BackgroundThe Sudan virus (SUDV) outbreaks in recent years including the ongoing outbreak in Uganda created a public health emergency beyond the Eastern Africa region. Currently, there are licensed countermeasures for Ebola virus (EBOV); however, there are no licensed vaccines or therapeutics against SUDV. MethodsWe developed a vesicular stomatitis virus (VSV)-based vaccine expressing the SUDV glycoprotein. Cynomolgus macaques were vaccinated intramuscularly with a single dose of VSV-SUDV either one month or one week prior to SUDV challenge. A third group was vaccinated with a single dose of VSV-EBOV one month prior to SUDV challenge to assess its cross-protective potential, and a control group received an unrelated VSV-based vaccine. ResultsAll vaccinated nonhuman primates (NHPs) developed antigen-specific IgG within 2 weeks of vaccination, including cross-reactive responses. After challenge with a lethal dose of SUDV, all VSV-SUDV-vaccinated NHPs were uniformly protected from disease. In contrast, the VSV-EBOV-vaccinated and control NHPs succumbed to disease between day 5 and 7 after challenge presenting with classical signs of Sudan virus disease associated with high titer viremia, high viral organ load, dysregulated cytokine profiles and typical pathological changes. The humoral immune response in the NHPs vaccinated with VSV-SUDV one month before challenge resulted in a profound and sustained antibody response with a diverse functionality profile which was not observed to the same extend in NHPs vaccinated one week before challenge. InterpretationWe demonstrated that a single dose of VSV-SUDV protected NHPs from lethal SUDV infection within one week. The fast-acting nature makes VSV-SUDV an ideal countermeasure for ring vaccination during outbreaks of Sudan virus disease. In contrast, VSV-EBOV provided no relevant protection against SUDV infection in NHPs highlighting the need for species-specific filovirus vaccines.

microbiology↗

bioRxiv2022

Rapid protection of nonhuman primates against Marburg virus disease using a single low-dose VSV-based vaccine

Marburg virus (MARV) is the causative agent of Marburg virus disease (MVD) which has a case fatality rate up to ~90% in humans. Recently, there were cases reported in Guinea and Ghana highlighting this virus as a high-consequence pathogen potentially threatening global public health. There are no licensed treatments or vaccines available today. We used a vesicular stomatitis virus (VSV)-based vaccine expressing the MARV-Angola glycoprotein (VSV-MARV) as the viral antigen. Previously, a single dose of 1x107 plaque-forming units (PFU) administered 7 days before challenge resulted in uniform protection from disease in cynomolgus macaques. Here, we sought to lower the vaccination dose to allow for more doses per vial in an emergency outbreak situation. We administered 1x105 or 1x103 PFU 14 days before challenge and achieved uniform protection in both groups. When we administered 1x103 PFU 7 days before challenge, vaccination resulted in uniform protection with no detectable viremia. Antigen-specific IgG responses were induced by both vaccine concentrations and were sustained until the study endpoint. Neutralizing antibody responses and antibody-dependent cellular phagocytosis were observed with both vaccination doses and timelines. The cellular response after vaccination was characterized by early induction of NK cell activation. Additionally, antigen-specific memory T cell subsets were detected in all vaccination cohorts indicating that while the primary protective mechanism of VSV-MARV is the humoral response, a functional cellular response is also induced. Overall, this data highlights VSV-MARV as a viable and fast-acting MARV vaccine candidate suitable for deployment in emergency outbreak situations and supports its clinical development. One Sentence SummaryA single low dose of VSV-MARV administered 14 or 7 days before challenge protects NHPs uniformly from lethal disease.

immunology↗

bioRxiv2021

Serum from COVID-19 patients early in the pandemic shows limited evidence of cross-neutralization against variants of concern

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) results in a variety of clinical symptoms ranging from no or mild to severe disease. Currently, there are multiple postulated mechanisms that may push a moderate to severe disease into a critical state. Human serum contains abundant evidence of the immune status following infection. Cytokines, chemokines, and antibodies can be assayed to determine the extent to which a patient responded to a pathogen. We examined serum and plasma from a cohort of patients infected with SARS-CoV-2 early in the pandemic and compared them to negative-control sera. Cytokine and chemokine concentrations varied depending on the severity of infection, and antibody responses were significantly increased in severe cases compared to mild to moderate infections. Neutralization data revealed that patients with high titers against an early 2020 isolate had detectable but limited neutralizing antibodies against newly circulating SARS-CoV-2 variants of concern. This study highlights the potential of re-infection for recovered COVID-19 patients.

microbiology↗

bioRxiv2021

Optimization of single dose VSV-based COVID-19 vaccination in hamsters

The ongoing COVID-19 pandemic has resulted in global effects on human health, economic stability, and social norms. The emergence of viral variants raises concerns about the efficacy of existing vaccines and highlights the continued need the for the development of efficient, fast-acting, and cost-effective vaccines. Here, we demonstrate the immunogenicity and protective efficacy of two vesicular stomatitis virus (VSV)-based vaccines encoding the SARS-CoV-2 spike protein either alone (VSV-SARS2) or in combination with the Ebola virus glycoprotein (VSV-SARS2-EBOV). Intranasally vaccinated hamsters showed an early CD8+ T cell response in the lungs and a greater antigen-specific IgG response, while intramuscularly vaccinated hamsters had an early CD4+ T cell and NK cell response. Intranasal vaccination resulted in protection within 10 days with hamsters not showing clinical signs of pneumonia when challenged with three different SARS-CoV-2 variants. This data demonstrates that VSV-based vaccines are viable single-dose, fast-acting vaccine candidates that are protective from COVID-19.

microbiology↗

bioRxiv2021

Pathogenic and transcriptomic differences of emerging SARS-CoV-2 variants in the Syrian golden hamster model

Following the discovery of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its rapid spread throughout the world, new viral variants of concern (VOC) have emerged. There is a critical need to understand the impact of the emerging variants on host response and disease dynamics to facilitate the development of vaccines and therapeutics. Syrian golden hamsters are the leading small animal model that recapitulates key aspects of severe coronavirus disease 2019 (COVID-19). In this study, we show that intranasal inoculation of SARS-CoV-2 into hamsters with the ancestral virus (nCoV-WA1-2020) or VOC first identified in the United Kingdom (B.1.1.7) and South Africa (B.1.351) led to similar gross and histopathologic pulmonary lesions. Although differences in viral genomic copy numbers were noted in the lungs and oral swabs of challenged animals, infectious titers in the lungs were comparable. Antibody neutralization capacities varied, dependent on the original challenge virus and cross-variant protective capacity. Transcriptional profiling indicated significant induction of antiviral pathways in response to all three challenges with a more robust inflammatory signature in response to B.1.1.7. Furthermore, no additional mutations in the spike protein were detected at peak disease. In conclusion, the emerging VOC showed distinct humoral responses and transcriptional profiles in the hamster model compared to the ancestral virus.

microbiology↗

bioRxiv2021

Training Data: How can we best prepare instructors to teach data science in undergraduate biology and environmental science courses?

There is a clear and concrete need for greater quantitative literacy in the biological and environmental sciences. Data science training for students in higher education necessitates well-equipped and confident instructors across curricula. However, not all instructors are versed in data science skills or research-based teaching practices. Our study sought to survey the state of data science education across institutions of higher learning, identify instructor needs, and illuminate barriers to teaching data science in the classroom. We distributed a survey to instructors around the world, focused on the United States, and received 106 complete responses. Our results indicate that instructors across institutions use, teach, and view data management, analysis, and visualization as important for students to learn. Code, modeling, and reproducibility were less valued by instructors, although there were differences by institution type (doctoral, masters, or baccalaureate), and career stage (time since terminal degree). While there were a variety of barriers highlighted by respondents, instructor background, student background, and space in the curriculum were the greatest barriers of note. Interestingly, instructors were most interested in receiving training for how to teach code and data analysis in the undergraduate classroom. Our study provides an important window into how data science is taught in higher education as well as suggestions for how we can best move forward with empowering instructors across disciplines.

scientific communication and education↗

bioRxiv2021

Rapid protection from COVID-19 in nonhuman primates vaccinated intramuscularly but not intranasally with a single dose of a recombinant vaccine

The ongoing pandemic of Coronavirus disease 2019 (COVID-19) continues to exert a significant burden on health care systems worldwide. With limited treatments available, vaccination remains an effective strategy to counter transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Recent discussions concerning vaccination strategies have focused on identifying vaccine platforms, number of doses, route of administration, and time to reach peak immunity against SARS-CoV-2. Here, we generated a single dose, fast-acting vesicular stomatitis virus-based vaccine derived from the licensed Ebola virus (EBOV) vaccine rVSV-ZEBOV, expressing the SARS-CoV-2 spike protein and the EBOV glycoprotein (VSV-SARS2-EBOV). Rhesus macaques vaccinated intramuscularly (IM) with a single dose of VSV-SARS2-EBOV were protected within 10 days and did not show signs of COVID-19 pneumonia. In contrast, intranasal (IN) vaccination resulted in limited immunogenicity and enhanced COVID-19 pneumonia compared to control animals. While IM and IN vaccination both induced neutralizing antibody titers, only IM vaccination resulted in a significant cellular immune response. RNA sequencing data bolstered these results by revealing robust activation of the innate and adaptive immune transcriptional signatures in the lungs of IM-vaccinated animals only. Overall, the data demonstrates that VSV-SARS2-EBOV is a potent single-dose COVID-19 vaccine candidate that offers rapid protection based on the protective efficacy observed in our study. One sentence summaryVSV vaccine protects NHPs from COVID-19 in 10 days

microbiology↗