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Article: A Bacteriophage Cocktail Targeting

Kilgore, Paul B / Sha, Jian / Hendrix, Emily K / Neil, Blake H / Lawrence, William S / Peel, Jennifer E / Hittle, Lauren / Woolston, Joelle / Sulakvelidze, Alexander / Schwartz, Jennifer A / Chopra, Ashok K

bioRxiv : the preprint server for biology

2024

Abstract: ... Yersinia ... ...

Abstract	Yersinia pestis
Language	English
Publishing date	2024-01-18
Publishing country	United States
Document type	Preprint
DOI	10.1101/2024.01.17.576055
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Article ; Online: Pathogenesis of Aerosolized Ebola Virus Variant Makona in Nonhuman Primates.

Prasad, Abhishek N / Fenton, Karla A / Agans, Krystle N / Borisevich, Viktoriya / Woolsey, Courtney / Comer, Jason E / Dobias, Natalie S / Peel, Jennifer E / Deer, Daniel J / Geisbert, Joan B / Lawrence, William S / Cross, Robert W / Geisbert, Thomas W

The Journal of infectious diseases

2023 Volume 228, Issue Suppl 7, Page(s) S604–S616

Abstract: Background: Highly pathogenic filoviruses such as Ebola virus (EBOV) hold capacity for delivery by artificial aerosols, and thus potential for intentional misuse. Previous studies have shown that high doses of EBOV delivered by small-particle aerosol ... ...

Abstract	Background: Highly pathogenic filoviruses such as Ebola virus (EBOV) hold capacity for delivery by artificial aerosols, and thus potential for intentional misuse. Previous studies have shown that high doses of EBOV delivered by small-particle aerosol cause uniform lethality in nonhuman primates (NHPs), whereas only a few small studies have assessed lower doses in NHPs. Methods: To further characterize the pathogenesis of EBOV infection via small-particle aerosol, we challenged cohorts of cynomolgus monkeys with low doses of EBOV variant Makona, which may help define risks associated with small particle aerosol exposures. Results: Despite using challenge doses orders of magnitude lower than previous studies, infection via this route was uniformly lethal across all cohorts. Time to death was delayed in a dose-dependent manner between aerosol-challenged cohorts, as well as in comparison to animals challenged via the intramuscular route. Here, we describe the observed clinical and pathological details including serum biomarkers, viral burden, and histopathological changes leading to death. Conclusions: Our observations in this model highlight the striking susceptibility of NHPs, and likely humans, via small-particle aerosol exposure to EBOV and emphasize the need for further development of diagnostics and postexposure prophylactics in the event of intentional release via deployment of an aerosol-producing device.
MeSH term(s)	Humans ; Animals ; Ebolavirus ; Hemorrhagic Fever, Ebola ; Macaca fascicularis ; Aerosols ; Viral Load
Chemical Substances	Aerosols
Language	English
Publishing date	2023-05-05
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	3019-3
ISSN	1537-6613 ; 0022-1899
ISSN (online)	1537-6613
ISSN	0022-1899
DOI	10.1093/infdis/jiad137
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Article ; Online: Long-term Prophylaxis Against Aerosolized Marburg Virus in Nonhuman Primates With an Afucosylated Monoclonal Antibody.

The Journal of infectious diseases

2023 Volume 228, Issue Suppl 7, Page(s) S701–S711

Abstract: Marburg virus (MARV) causes a hemorrhagic fever disease in human and nonhuman primates with high levels of morbidity and mortality. Concerns about weaponization of aerosolized MARV have spurred the development of nonhuman primate (NHP) models of aerosol ... ...

Abstract	Marburg virus (MARV) causes a hemorrhagic fever disease in human and nonhuman primates with high levels of morbidity and mortality. Concerns about weaponization of aerosolized MARV have spurred the development of nonhuman primate (NHP) models of aerosol exposure. To address the potential threat of aerosol exposure, a monoclonal antibody that binds MARV glycoprotein was tested, MR186YTE, for its efficacy as a prophylactic. MR186YTE was administered intramuscularly to NHPs at 15 or 5 mg/kg 1 month prior to MARV aerosol challenge. Seventy-five percent (3/4) of the 15 mg/kg dose group and 50% (2/4) of the 5 mg/kg dose group survived. Serum analyses showed that the NHP dosed with 15 mg/kg that succumbed to infection developed an antidrug antibody response and therefore had no detectable MR186YTE at the time of challenge. These results suggest that intramuscular dosing of mAbs may be a clinically useful prophylaxis for MARV aerosol exposure.
MeSH term(s)	Animals ; Humans ; Marburgvirus ; Marburg Virus Disease ; Antibodies, Monoclonal ; Primates ; Aerosols
Chemical Substances	Antibodies, Monoclonal ; Aerosols
Language	English
Publishing date	2023-07-18
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	3019-3
ISSN	1537-6613 ; 0022-1899
ISSN (online)	1537-6613
ISSN	0022-1899
DOI	10.1093/infdis/jiad278
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Article: Teixobactin Provides Protection against Inhalation Anthrax in the Rabbit Model.

Lawrence, William S / Peel, Jennifer E / Sivasubramani, Satheesh K / Baze, Wallace B / Whorton, Elbert B / Beasley, David W C / Comer, Jason E / Hughes, Dallas E / Ling, Losee L / Peterson, Johnny W

Pathogens (Basel, Switzerland)

2020 Volume 9, Issue 9

Abstract: The use of antibiotics is a vital means of treating infections caused by the ... ...

Abstract	The use of antibiotics is a vital means of treating infections caused by the bacteria
Language	English
Publishing date	2020-09-22
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2695572-6
ISSN	2076-0817
ISSN	2076-0817
DOI	10.3390/pathogens9090773
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Article ; Online: Venezuelan equine encephalitis vaccine with rearranged genome resists reversion and protects non-human primates from viremia after aerosol challenge.

Tretyakova, Irina / Plante, Kenneth S / Rossi, Shannan L / Lawrence, William S / Peel, Jennifer E / Gudjohnsen, Sif / Wang, Eryu / Mirchandani, Divya / Tibbens, Alexander / Lamichhane, Tek N / Lukashevich, Igor S / Comer, Jason E / Weaver, Scott C / Pushko, Peter

Vaccine

2020 Volume 38, Issue 17, Page(s) 3378–3386

Abstract: Live-attenuated V4020 vaccine for Venezuelan equine encephalitis virus (VEEV) containing attenuating rearrangement of the virus structural genes was evaluated in a non-human primate model for immunogenicity and protective efficacy against aerosol ... ...

Abstract	Live-attenuated V4020 vaccine for Venezuelan equine encephalitis virus (VEEV) containing attenuating rearrangement of the virus structural genes was evaluated in a non-human primate model for immunogenicity and protective efficacy against aerosol challenge with wild-type VEEV. The genomic RNA of V4020 vaccine virus was encoded in the pMG4020 plasmid under control of the CMV promoter and contained the capsid gene downstream from the glycoprotein genes. It also included attenuating mutations from the VEE TC83 vaccine, with E2-120Arg substitution genetically engineered to prevent reversion mutations. The population of V4020 vaccine virus derived from pMG4020-transfected Vero cells was characterized by next generation sequencing (NGS) and indicated no detectable genetic reversions. Cynomolgus macaques were vaccinated with V4020 vaccine virus. After one or two vaccinations including by intramuscular route, high levels of virus-neutralizing antibodies were confirmed with no viremia or apparent adverse reactions to vaccinations. The protective effect of vaccination was evaluated using an aerosol challenge with VEEV. After challenge, macaques had no detectable viremia, demonstrating a protective effect of vaccination with live V4020 VEEV vaccine.
MeSH term(s)	Aerosols ; Animals ; Antibodies, Neutralizing/blood ; Antibodies, Viral/blood ; Chlorocebus aethiops ; Encephalitis Virus, Venezuelan Equine/genetics ; Encephalitis Virus, Venezuelan Equine/immunology ; Encephalomyelitis, Venezuelan Equine/prevention & control ; Macaca ; Vero Cells ; Viral Vaccines/genetics ; Viral Vaccines/immunology ; Viremia/prevention & control
Chemical Substances	Aerosols ; Antibodies, Neutralizing ; Antibodies, Viral ; Viral Vaccines
Language	English
Publishing date	2020-02-19
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	605674-x
ISSN	1873-2518 ; 0264-410X
ISSN (online)	1873-2518
ISSN	0264-410X
DOI	10.1016/j.vaccine.2020.02.007
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Article: Teixobactin Provides Protection against Inhalation Anthrax in the Rabbit Model

Lawrence, William S / Peel, Jennifer E / Sivasubramani, Satheesh K / Baze, Wallace B / Whorton, Elbert B / Beasley, David W. C / Comer, Jason E / Hughes, Dallas E / Ling, Losee L / Peterson, Johnny W

Pathogens. 2020 Sept. 22, v. 9, no. 9

2020

Abstract: The use of antibiotics is a vital means of treating infections caused by the bacteria Bacillus (B.) anthracis. Importantly, with the potential future use of multidrug-resistant strains of B. anthracis as bioweapons, new antibiotics are needed as ... ...

Abstract	The use of antibiotics is a vital means of treating infections caused by the bacteria Bacillus (B.) anthracis. Importantly, with the potential future use of multidrug-resistant strains of B. anthracis as bioweapons, new antibiotics are needed as alternative therapeutics. In this blinded study, we assessed the protective efficacy of teixobactin, a recently discovered antibiotic, against inhalation anthrax infection in the adult rabbit model. New Zealand White rabbits were infected with a lethal dose of B. anthracis Ames spores via the inhalation route, and blood samples were collected at various times to assess antigenemia, bacteremia, tissue bacterial load, and antibody production. Treatments were administered upon detection of B. anthracis protective antigen in the animals’ sera. For comparison, a fully protective dose of levofloxacin was used as a positive control. Rabbits treated with teixobactin showed 100% survival following infection, and the bacteremia was completely resolved by 24–48 h post-treatment. In addition, the bacterial/spore loads in tissues of the animals treated with teixobactin were either zero or dramatically less relative to that of the negative control animals. Moreover, microscopic evaluation of the tissues revealed decreased pathology following treatment with teixobactin. Overall, these results show that teixobactin was protective against inhalation anthrax infection in the rabbit model, and they indicate the potential of teixobactin as a therapeutic for the disease.
Keywords	adults ; anthrax ; antibody formation ; antigens ; bacteremia ; blood sampling ; breathing ; detection ; dosage ; lethal dose ; levofloxacin ; microbial load ; models ; multiple drug resistance ; pathogens ; rabbits ; spores ; strains ; tissues
Language	English
Dates of publication	2020-0922
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
Note	NAL-light
ZDB-ID	2695572-6
ISSN	2076-0817
ISSN	2076-0817
DOI	10.3390/pathogens9090773
Database	NAL-Catalogue (AGRICOLA)

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Article: Venezuelan equine encephalitis vaccine with rearranged genome resists reversion and protects non-human primates from viremia after aerosol challenge

Vaccine. 2020 Apr. 09, v. 38, no. 17

2020

Abstract	Live-attenuated V4020 vaccine for Venezuelan equine encephalitis virus (VEEV) containing attenuating rearrangement of the virus structural genes was evaluated in a non-human primate model for immunogenicity and protective efficacy against aerosol challenge with wild-type VEEV. The genomic RNA of V4020 vaccine virus was encoded in the pMG4020 plasmid under control of the CMV promoter and contained the capsid gene downstream from the glycoprotein genes. It also included attenuating mutations from the VEE TC83 vaccine, with E2-120Arg substitution genetically engineered to prevent reversion mutations. The population of V4020 vaccine virus derived from pMG4020-transfected Vero cells was characterized by next generation sequencing (NGS) and indicated no detectable genetic reversions. Cynomolgus macaques were vaccinated with V4020 vaccine virus. After one or two vaccinations including by intramuscular route, high levels of virus-neutralizing antibodies were confirmed with no viremia or apparent adverse reactions to vaccinations. The protective effect of vaccination was evaluated using an aerosol challenge with VEEV. After challenge, macaques had no detectable viremia, demonstrating a protective effect of vaccination with live V4020 VEEV vaccine.
Keywords	Macaca fascicularis ; RNA ; Venezuelan equine encephalitis virus ; adverse effects ; aerosols ; animal models ; antibodies ; capsid ; encephalitis ; genetic engineering ; genomics ; glycoproteins ; high-throughput nucleotide sequencing ; horses ; immunogenicity ; live vaccines ; mutation ; plasmids ; protective effect ; structural genes ; vaccination ; viremia ; viruses
Language	English
Dates of publication	2020-0409
Size	p. 3378-3386.
Publishing place	Elsevier Ltd
Document type	Article
ZDB-ID	605674-x
ISSN	1873-2518 ; 0264-410X
ISSN (online)	1873-2518
ISSN	0264-410X
DOI	10.1016/j.vaccine.2020.02.007
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Catch and kill airborne SARS-CoV-2 to control spread of COVID-19 by a heated air disinfection system

Yu, Luo / Peel, Garrett K. / Cheema, Faisal H. / Lawrence, William S. / Bukreyeva, Natalya / Jinks, Christopher W. / Peel, Jennifer E. / Peterson, Johnny W. / Paessler, Slobodan / Hourani, Monzer / Ren, Zhifeng

bioRxiv

Abstract: Airborne transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) via air-conditioning systems poses a significant threat for the continued escalation of the current coronavirus disease (COVID-19) pandemic. Considering that SARS-CoV-2 ...

Abstract	Airborne transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) via air-conditioning systems poses a significant threat for the continued escalation of the current coronavirus disease (COVID-19) pandemic. Considering that SARS-CoV-2 cannot tolerate temperatures above 70 degree C, here we designed and fabricated efficient air disinfection systems based on heated nickel (Ni) foam to catch and kill SARS-CoV-2. Virus test results revealed that 99.8% of the aerosolized SARS-CoV-2 was caught and killed by a single pass through a Ni-foam-based filter when heated up to 200 degree C. Additionally, the same filter was also used to catch and kill 99.9% of Bacillus anthracis, an airborne spore. This study paves the way for preventing transmission of SARS-CoV-2 and other highly infectious airborne agents in closed environments.
Keywords	covid19
Language	English
Publishing date	2020-06-16
Publisher	Cold Spring Harbor Laboratory
Document type	Article ; Online
DOI	10.1101/2020.06.13.150243
Database	COVID19

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Article ; Online: Catch and kill airborne SARS-CoV-2 to control spread of COVID-19 by a heated air disinfection system

bioRxiv

Abstract	Airborne transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) via air-conditioning systems poses a significant threat for the continued escalation of the current coronavirus disease (COVID-19) pandemic. Considering that SARS-CoV-2 cannot tolerate temperatures above 70 °C, here we designed and fabricated efficient air disinfection systems based on heated nickel (Ni) foam to catch and kill SARS-CoV-2. Virus test results revealed that 99.8% of the aerosolized SARS-CoV-2 was caught and killed by a single pass through a Ni-foam-based filter when heated up to 200 °C. Additionally, the same filter was also used to catch and kill 99.9% of Bacillus anthracis, an airborne spore. This study paves the way for preventing transmission of SARS-CoV-2 and other highly infectious airborne agents in closed environments. One Sentence Summary Heated Ni-foam filters are capable of effectively catching and killing airborne SARS-CoV-2 and Bacillus anthracis spores.
Keywords	covid19
Publisher	BioRxiv; WHO
Document type	Article ; Online
DOI	10.1101/2020.06.13.150243
Database	COVID19

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Article ; Online: Experimental Infection of Syrian Hamsters With Aerosolized Nipah Virus.

Escaffre, Olivier / Hill, Terence / Ikegami, Tetsuro / Juelich, Terry L / Smith, Jennifer K / Zhang, Lihong / Perez, David E / Atkins, Colm / Park, Arnold / Lawrence, William S / Sivasubramani, Satheesh K / Peel, Jennifer E / Peterson, Johnny W / Lee, Benhur / Freiberg, Alexander N

The Journal of infectious diseases

2018 Volume 218, Issue 10, Page(s) 1602–1610

Abstract: Background: Nipah virus (NiV) is a paramyxovirus (genus Henipavirus) that can cause severe respiratory illness and encephalitis in humans. Transmission occurs through consumption of NiV-contaminated foods, and contact with NiV-infected animals or human ... ...

Abstract	Background: Nipah virus (NiV) is a paramyxovirus (genus Henipavirus) that can cause severe respiratory illness and encephalitis in humans. Transmission occurs through consumption of NiV-contaminated foods, and contact with NiV-infected animals or human body fluids. However, it is unclear whether aerosols derived from aforesaid sources or others also contribute to transmission, and current knowledge on NiV-induced pathogenicity after small-particle aerosol exposure is still limited. Methods: Infectivity, pathogenicity, and real-time dissemination of aerosolized NiV in Syrian hamsters was evaluated using NiV-Malaysia (NiV-M) and/or its recombinant expressing firefly luciferase (rNiV-FlucNP). Results: Both viruses had an equivalent pathogenicity in hamsters, which developed respiratory and neurological symptoms of disease, similar to using intranasal route, with no direct correlations to the dose. We showed that virus replication was predominantly initiated in the lower respiratory tract and, although delayed, also intensely in the oronasal cavity and possibly the brain, with gradual increase of signal in these regions until at least day 5-6 postinfection. Conclusion: Hamsters infected with small-particle aerosolized NiV undergo similar clinical manifestations of the disease as previously described using liquid inoculum, and exhibit histopathological lesions consistent with NiV patient reports. NiV droplets could therefore play a role in transmission by close contact.
MeSH term(s)	Administration, Inhalation ; Aerosols/administration & dosage ; Animals ; Cricetinae ; Disease Models, Animal ; Henipavirus Infections/diagnostic imaging ; Henipavirus Infections/pathology ; Henipavirus Infections/transmission ; Henipavirus Infections/virology ; Luciferases, Firefly/genetics ; Luciferases, Firefly/metabolism ; Lung/diagnostic imaging ; Lung/pathology ; Lung/virology ; Mesocricetus ; Nipah Virus/pathogenicity ; Optical Imaging ; Recombinant Proteins/genetics ; Recombinant Proteins/metabolism
Chemical Substances	Aerosols ; Recombinant Proteins ; Luciferases, Firefly (EC 1.13.12.7)
Language	English
Publishing date	2018-02-13
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	3019-3
ISSN	1537-6613 ; 0022-1899
ISSN (online)	1537-6613
ISSN	0022-1899
DOI	10.1093/infdis/jiy357
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