Previous studies demonstrated that a single intramuscular (i.m.) dose of an attenuated recombinant vesicular stomatitis virus (rVSV) vector (VesiculoVax vector platform; rVSV-N4CT1) expressing the glycoprotein (GP) from the Mayinga strain of Zaire ebolavirus (EBOV) protected nonhuman primates (NHPs) from lethal challenge with EBOV strains Kikwit and Makona. Here, we studied the immunogenicities of an expanded range of attenuated rVSV vectors expressing filovirus GP in mice. Based on data from those studies, an optimal attenuated trivalent rVSV vector formulation was identified that included rVSV vectors expressing EBOV, Sudan ebolavirus (SUDV), and the Angola strain of Marburg marburgvirus (MARV) GPs. NHPs were vaccinated with a single dose of the trivalent formulation, followed by lethal challenge 28 days later with each of the three corresponding filoviruses. At day 14 postvaccination, a serum IgG response specific for all three GPs was detected in all the vaccinated macaques. A modest and balanced cell-mediated immune response specific for each GP was also detected in a majority of the vaccinated macaques. No matter the level of total GP-specific immune response detected postvaccination, all the vaccinated macaques were protected from disease and death following lethal challenge with each of the three filoviruses. These findings indicate that vaccination with a single dose of attenuated rVSV-N4CT1 vectors each expressing a single filovirus GP may provide protection against the filoviruses most commonly responsible for outbreaks of hemorrhagic fever in sub-Saharan Africa.IMPORTANCE The West African Ebola virus Zaire outbreak in 2013 showed that the disease was not only a regional concern, but a worldwide problem, and highlighted the need for a safe and efficacious vaccine to be administered to the populace. However, other endemic pathogens, like Ebola virus Sudan and Marburg, also pose an important health risk to the public and therefore require development of a vaccine prior to the occurrence of an outbreak. The significance of our research was the development of a blended trivalent filovirus vaccine that elicited a balanced immune response when administered as a single dose and provided complete protection against a lethal challenge with all three filovirus pathogens.
The inactivation of Bacillus anthracis spores on subway and used subway railcar materials was evaluated using fogged peracetic acid/hydrogen peroxide (PAA) and hydrogen peroxide (HO). A total of 21 separate decontamination tests were conducted using bacterial spores of both B. anthracis Ames (B.a.) and Bacillus atrophaeus (B.g.) inoculated onto several types of materials. Tests were conducted using commercial off-the-shelf fogging equipment filled with either PAA or HO to fumigate a ∼15 cubic meter chamber under uncontrolled ambient relative humidity and controlled temperature (10 or 20 °C) from 8 to 168 h. For the present study, no conditions were found that resulted in complete inactivation of either B.a. Ames or B.g. on all test materials. Approximately 41% and 38% of the decontamination efficacies for B.a. and B.g., respectively, exhibited ≥6 log reduction (LR); efficacy depended greatly on the material. When testing at 10 °C, the mean LR was consistently lower for both B.a. and B.g. as compared to 20 °C. Based on the statistical comparison of the LR results, B.g. exhibited equivalent or greater resistance than B.a. for approximately 92% of the time across all 21 tests. The efficacy data suggest that B.g. may be a suitable surrogate for B.a. Ames when assessing the decontamination efficacy of fogged PAA or HO. Moreover, the results of this testing indicate that in the event of B.a. spore release into a subway system, the fogging of PAA or HO represents a decontamination option for consideration.
Within the past decade, human infections with the highly pathogenic avian influenza H5N1 have resulted in approximately 60% mortality and increased the need for vaccines and therapeutics. Understanding the molecular events associated with pathology can aid this effort; therefore, this study was conducted to assess microRNA (miRNA) expression in mouse lungs infected with H5N1 A/Vietnam/1203/04. Intranasal administration of 1500 median tissue culture infectious dose of H5N1 promoted differences in the number and expression pattern of miRNA from lung tissue collected at 2, 4, 6, 24, and 96 h post-exposure that mapped to common biological functions. Informatics analysis identified miRNA-specific predicted genes known to be therapeutic drug targets in which Furin was common to all time periods. This study provides insight into the differential miRNA expression with respect to the host-pathogen relationship and identification of potential therapeutic drug targets.
Significance and Impact of the Study: Smallpox is caused by the variola virus, and ranks as one of the most serious diseases that could originate from a biological weapon. However, limited data exist on the persistence of variola and related viruses (such as vaccinia, an established surrogate) on materials that may act as fomites. Persistence data are also inadequate for these viruses under controlled environmental conditions. The results from this study will fill some of these data gaps and may aid those responsible for infection control to make informed decisions regarding the need for decontamination after the release of a biological agent such as variola. AbstractSmallpox is caused by the variola virus, and ranks as one of the most serious diseases that could originate from a biological weapon. However, limited data exist on the persistence of variola and related viruses on materials (that may act as fomites), under controlled environmental conditions. To fill these data gaps, we determined the persistence of the vaccinia virus (an established surrogate for the variola virus) as a function of temperature, relative humidity and material. Experiments were conducted with vaccinia virus in a freeze-dried form, using four materials under four sets of environmental conditions. After elapsed times ranging from 1 to 56 days, the virus was extracted from small coupons and quantified via plaque-forming units (PFU). The vaccinia virus was most persistent at low temperature and low relative humidity, with greater than 10 4 PFU recovered from glass, galvanized steel and painted cinder block at 56 days (equivalent to only a c. 2 log reduction). Thus, vaccinia virus may persist from weeks to months, depending on the material and environmental conditions. This study may aid those responsible for infection control to make informed decisions regarding the need for environmental decontamination following the release of an agent such as variola.
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