Biology subjects

Gourdine, T.

Publications and source records attributed to Gourdine, T..

4 recordsLinked to original sources

bioRxiv2026

Preexisting chronic infection skews the epigenetic landscape of subsequent memory CD8 T cell responses

Previous studies suggest that preexisting chronic disease impairs immune responses to subsequent infection and vaccination. However, the underlying epigenetic mechanisms are understudied. Here, we show that preexisting chronic infection with LCMV clone 13 (CL13) compromised the formation of central memory CD8 T cells (TCM) to subsequent Listeria monocytogenes infection, despite not profoundly impacting effector responses. This correlated with a skewed cytokine milieu. Our chromatin-accessibility profiling of Listeria-specific CD8 T cells showed significant epigenetic skewing of both TCM and effector memory (TEM) in mice with preexisting LCMV-CL13, a skewing that started in memory-precursor effector cells (MPECs) during the effector phase. Transcription-factor binding sites (TFBS) analyses highlighted the interferon regulatory factor (IRF) family as major TFs implicated in this skewing. Thus, our results suggest that preexisting persistent inflammation skews the phenotypic and epigenetic landscape of subsequent memory responses, arguing for interventions to optimize vaccine-induced memory in hosts with preexisting chronic disease.

immunology↗

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

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↗