Publications
Resistance to antiviral treatments like nirmatrelvir-ritonavir (NIR-RIT) poses a growing challenge in managing SARS-CoV-2 infections. In this study, researchers identified two new SARS-CoV-2 main protease (Mpro) variants from patients who remained positive after NIR-RIT treatment. Despite being located far from the enzyme’s active site, these mutations conferred full resistance to NIR without reducing the protease’s normal function. Structural and biochemical analyses suggest the mutations affect the enzyme’s shape and stability in ways that limit drug binding. These findings highlight the need for ongoing surveillance of resistance mutations and support the development of next-generation antivirals targeting SARS-CoV-2.
“Functional and Structural Characterization of Treatment-Emergent Nirmatrelvir Resistance Mutations at Low Frequencies in the Main Protease (Mpro) Reveals a Unique Evolutionary Route for SARS-CoV-2 to Gain Resistance”
People living with HIV represent a significant proportion of mpox cases, yet little is known about how HIV co-infection affects mpox at the molecular level. Using dual RNA sequencing of skin lesion samples from individuals with and without HIV, this study revealed that HIV-positive participants had increased expression of monkeypox virus genes tied to immune evasion and replication, alongside suppressed host immune responses. These results suggest that HIV-related immunosuppression may worsen mpox infection by enabling greater viral activity. This work provides new insights into mpox pathogenesis and highlights the importance of tailored clinical strategies for immunocompromised populations.
“Monkeypox virus transcriptional profiles and host responses in skin lesion swabs among individuals with HIV”
“Stability of Monkeypox Virus on Commonly Contacted Surfaces in Clinical Settings”
Understanding how long monkeypox virus (MPXV) remains infectious on surfaces is critical for infection control, especially in clinical settings. This study assessed the stability of MPXV on both porous and nonporous materials at different temperatures over 21 days. Results showed that MPXV survives longer on nonporous surfaces and at cooler temperatures, with viable virus persisting up to three weeks on intravenous tubing and nitrile gloves at 4 °C. Importantly, viral DNA detection did not always reflect the presence of infectious virus, suggesting that molecular tests may overestimate surface transmission risks. These findings inform decontamination strategies and highlight the need for refined approaches to assess fomite-mediated transmission.
“Vaccination against SARS-CoV-2 provides low-level cross-protection against common cold coronaviruses in mouse and non-human primate animal models”
Cross-protective immunity against seasonal coronaviruses remains an unmet challenge in vaccine development. In this study, a recombinant fowl adenovirus vaccine expressing the SARS-CoV-2 spike protein (FAdV-9-S19) was evaluated for its ability to protect against both SARS-CoV-2 and common cold coronaviruses. In mouse and non-human primate models, FAdV-9-S19 vaccination reduced viral shedding and lung inflammation following challenge with multiple seasonal coronaviruses, including HCoV-OC43, HCoV-NL63, and HCoV-229E. These findings support the potential of SARS-CoV-2-based platforms to confer partial cross-protection and inform future pan-coronavirus vaccine strategies.
“Comparison of a SARS-CoV-2 mRNA booster immunization containing additional antigens to a spike-based mRNA vaccine against Omicron BA.5 infection in hACE2 mice”
The emergence of SARS-CoV-2 variants presents challenges to vaccine effectiveness, underlining the necessity for next-generation vaccines with multiple antigens beyond the spike protein. Here, we investigated a multiantigenic booster containing spike and a chimeric construct composed of nucleoprotein (N) and membrane (M) proteins, comparing its efficacy to a spike-only booster against Omicron BA.5 in K18-hACE2 mice. This work highlights a promising strategy for individuals previously vaccinated with spike-only vaccines, potentially offering enhanced protection against emerging coronaviruses.
Globally, Creutzfeldt-Jakob disease (CJD) affects one in one million people annually, but there is a paucity of recent Canadian data. This study summarizes epidemiology trends and diagnostic timelines of laboratory-confirmed CJD cases in three tertiary Ontario hospitals. This study highlights the importance of early CJD consideration and laboratory testing when appropriate neurologic symptoms are present.
“Characterization of Laboratory-Confirmed Creutzfeldt-Jakob Disease From 3 Ontario Tertiary Care Centers Between 2012 and 2022: A Retrospective Cohort Study”
Uncovering early gene pathway abnormalities associated with eventual long COVID diagnosis may aid in early identification. We show that, post acute infection, in situ pathogenic deviations in viral response are associated with patients destined to meet consensus long COVID diagnosis that is entirely dependent on clinical factors.
“Differential Gene Expression in the Upper Respiratory Tract following Acute COVID-19 Infection in Ambulatory Patients That Develop Long COVID”
We present a descriptive analysis of quantitative MPXV DNA detection over time across multiple specimen types in adults with mpox infection. Our primary objective was to quantify the time from symptom onset to resolution of detectable viral DNA during acute mpox infection by specimen type. Our secondary objective was to estimate the proportion of participants with detectable DNA at study entry and at 1 week after complete clinical resolution by specimen type.
“Longitudinal Analysis of Mpox Virus DNA Detectability From Multiple Specimen Types During Acute Illness: A Cohort Study”
“BCG administration promotes the long-term protection afforded by a single-dose intranasal adenovirus-based SARS-CoV-2 vaccine”
Here, we investigate the immunomodulatory effects of Mycobacterium bovis BCG pre-immunization followed by vaccination with an S-protein-expressing i.n. Ad, termed Ad(Spike). While i.n. Ad(Spike) retains some protective effect after 6 months, a single administration of BCG-Danish prior to Ad(Spike) potentiates its ability to control viral replication of the B.1.351 SARS-CoV-2 variant within the respiratory tract.
“A novel intradermal tattoo-based injection device enhances the immunogenicity of plasmid DNA vaccines”
In recent years, tattooing technology has shown promising results toward evaluating vaccines in both animal models and humans. However, this technology has some limitations due to variability of experimental evaluations or operator procedures. The current study evaluated a device (intradermal oscillating needle array injection device: IONAID) capable of microinjecting a controlled dose of any aqueous vaccine into the intradermal space.
“Cross-reactive immunity against SARS-CoV-2 N protein in Central and West Africa precedes the COVID-19 pandemic”
Early predictions forecasted large numbers of severe acute respiratory syndrome coronavirus (SARS-CoV-2) cases and associated deaths in Africa. To date, Africa has been relatively spared. Various hypotheses were postulated to explain the lower than anticipated impact on public health in Africa. However, the contribution of pre-existing immunity is yet to be investigated. In this study, the presence of antibodies against SARS-CoV-2 spike (S) and nucleocapsid (N) proteins in pre-pandemic samples from Africa, Europe, South and North America was examined by ELISA.
“Two DNA vaccines protect against severe disease and pathology due to SARS-CoV-2 in Syrian hamsters”
The SARS-CoV-2 pandemic is an ongoing threat to global health, and wide-scale vaccination is an efficient method to reduce morbidity and mortality. We designed and evaluated two DNA plasmid vaccines, based on the pIDV-II system, expressing the SARS-CoV-2 spike gene, with or without an immunogenic peptide, in mice, and in a Syrian hamster model of infection.
Safe and effective vaccines are needed to end the COVID-19 pandemic. Here, we report the preclinical development of a lipid nanoparticle–formulated SARS-CoV-2 mRNA vaccine, PTX-COVID19-B. PTX-COVID19-B was chosen among three candidates after the initial mouse vaccination results showed that it elicited the strongest neutralizing antibody response against SARS-CoV-2.
“Preclinical evaluation of a SARS-CoV-2 mRNA vaccine PTX-COVID19-B”
