RESULTS:
1 - 4 of 4 for "Victoria A. Olson"
Evaluation of smallpox vaccines using variola neutralization
The search for a ‘third’-generation smallpox vaccine has resulted in the development and characterization of several vaccine candidates. A significant barrier to acceptance is the absence of challenge models showing induction of correlates of protective immunity against variola virus. In this light virus neutralization provides one of few experimental methods to show specific ‘in vitro’ activity of vaccines against variola virus. Here we provide characterization of the ability of a modified vaccinia virus Ankara vaccine to induce variola virus-neutralizing antibodies and we provide comparison with the neutralization elicited by standard Dryvax vaccination.
Smallpox virus plaque phenotypes: genetic, geographical and case fatality relationships
Smallpox (infection with Orthopoxvirus variola) remains a feared illness more than 25 years after its eradication. Historically case-fatality rates (CFRs) varied between outbreaks (<1 to ∼40 %) the reasons for which are incompletely understood. The extracellular enveloped virus (EEV) form of orthopoxvirus progeny is hypothesized to disseminate infection. Investigations with the closely related Orthopoxvirus vaccinia have associated increased comet formation (EEV production) with increased mouse mortality (pathogenicity). Other vaccinia virus genetic manipulations which affect EEV production inconsistently support this association. However antisera against vaccinia virus envelope protect mice from lethal challenge further supporting a critical role for EEV in pathogenicity. Here we show that the increased comet formation phenotypes of a diverse collection of variola viruses associate with strain phylogeny and geographical origin but not with increased outbreak-related CFRs; within clades there may be an association of plaque size with CFR. The mechanisms for variola virus pathogenicity probably involves multiple host and pathogen factors.
A prairie dog animal model of systemic orthopoxvirus disease using West African and Congo Basin strains of monkeypox virus
Multiple monkeypox virus (MPXV) animal models have been discussed in previous studies but no small animal models nor most non-human primate models demonstrated the protracted asymptomatic incubation phase seen in systemic human orthopoxvirus illness. Herein we characterize a black-tailed prairie dog (PD) (Cynomys ludovicianus) model of infection via intranasal and intradermal exposures with the two MPXV clades. Daily observations of the animals were made (food consumption general symptoms disease presentation) while weights and virus evaluations (ocular nasal oropharyngeal faeces blood) were obtained/made every third day. Generalized rash became apparent 9–12 days post-infection for all animals. Individual animals demonstrated a range of symptoms consistent with human monkeypox disease. Measurable viraemias and excretas were similar for both clade-representative strains and persisted until at least day 21. Greater morbidity was observed in Congo Basin strain-challenged animals and mortality was observed only in the Congo Basin strain-challenged animals. The PD model is valuable for the study of strain-dependent differences in MPXV. Additionally the model closely mimics human systemic orthopoxvirus disease and may serve as a valuable non-human surrogate for investigations of antivirals and next generation orthopoxvirus vaccines.
A tale of two clades: monkeypox viruses
Human monkeypox was first recognized outside Africa in 2003 during an outbreak in the USA that was traced to imported monkeypox virus (MPXV)-infected West African rodents. Unlike the smallpox-like disease described in the Democratic Republic of the Congo (DRC; a Congo Basin country) disease in the USA appeared milder. Here analyses compared clinical laboratory and epidemiological features of confirmed human monkeypox case-patients using data from outbreaks in the USA and the Congo Basin and the results suggested that human disease pathogenicity was associated with the viral strain. Genomic sequencing of USA Western and Central African MPXV isolates confirmed the existence of two MPXV clades. A comparison of open reading frames between MPXV clades permitted prediction of viral proteins that could cause the observed differences in human pathogenicity between these two clades. Understanding the molecular pathogenesis and clinical and epidemiological properties of MPXV can improve monkeypox prevention and control.