Povidone-iodine hand wash and hand rub products demonstrated excellent in vitro virucidal efficacy against Ebola virus and modified vaccinia virus Ankara, the new European test virus for enveloped viruses

ABSTRACT Orthopoxviruses commonly enter into humans and animals via the respiratory tract. Herein, we show that immigration of leukocytes into the lung is triggered via intranasal infection of mice with modified vaccinia virus Ankara (MVA) and not with the vaccinia virus (VACV) Elstree, Wyeth, or Western Reserve (WR) strain. Immigrating cells were identified as monocytes, neutrophils, and CD4+ lymphocytes by flow cytometry and could be detected 24 h and 48 h postinfection. Using an in vitro chemotaxis assay, we confirmed that infection with MVA induces the expression of a soluble chemotactic factor for monocytes, identified as CCL2 (monocyte chemotactic protein-1 [MCP-1]). In contrast to infection with several other VACV strains, MVA induced the expression of CCL2, CCL3, CCL4, and CXCL10 in the human monocytic cell line THP-1 as well as in primary human monocytes. Thus, MVA, and not the VACV Elstree, Wyeth, or WR strain, consistently triggered the expression of a panel of chemokines, including CCL2, in the murine lung, correlating considerably with the immigration of leukocytes. Using CCL2-deficient mice, we demonstrate that CCL2 plays a key role in MVA-triggered respiratory immigration of leukocytes. Moreover, UV irradiation of MVA prevented CCL2 expression in vitro and in vivo as well as respiratory immigration of leukocytes, demonstrating the requirement for an activated molecular viral life cycle. We propose that MVA-triggered chemokine expression causes early immigration of leukocytes to the site of infection, a feature that is important for rapid immunization and its safety and efficiency as a viral vector.

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Title: Bacteriophage Φ6 (Phi6) as a Surrogate for Enveloped Viral pathogens in Standard and Long-lasting Virucidal Efficacy Tests

10.21203/rs.3.rs-912169/v1 ◽

2021 ◽

Author(s):

Jaime B. Hutchison ◽

Chris Plummer ◽

Gareth Garner ◽

Amit Sehgal ◽

Laura B. Purevdorj-Gage ◽

...

Keyword(s):

Vaccinia Virus ◽

Quaternary Ammonium ◽

Viral Pathogens ◽

Enveloped Viruses ◽

Surface Stability ◽

Test Conditions ◽

The Uk ◽

First Time ◽

Ammonium Compounds ◽

Virucidal Efficacy

Abstract Development of novel antimicrobials capable of providing long-lasting disinfection on surfaces requires the implementation of new standardized methods to support claims recognized by regulatory authorities. Surrogates for viral pathogens are often desired in order for BSL-2 labs to conduct these new efficacy tests safely and efficiently, however, the knowledge of surrogate suitability for these tests is limited. Here, for the first time, we determine the resistance profile of the bacteriophage Phi6 to quaternary ammonium compounds (QACs) in a variety of test conditions. Additionally, we show that Phi6 can be used to demonstrate the long-lasting virucidal efficacy of a novel antimicrobial, Actizone™ F5, and that the Phi6 is more resistant to QACs following the UK standard long-lasting disinfection test BSI PAS2424:2014 than Vaccinia virus, which is the marker strain for claims of activity against enveloped viruses in Europe. Surface stability as well as benefits and limitations of Phi6 use relative to other enveloped viruses for antimicrobial testing is also discussed.

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Substitution of Vaccinia Virus Elstree by Modified Vaccinia Virus Ankara to test the Virucidal Efficacy of Chemical Disinfectants

Zoonoses and Public Health ◽

10.1111/j.1863-2378.2007.01094.x ◽

2008 ◽

Vol 55 (2) ◽

pp. 99-105 ◽

Cited By ~ 4

Author(s):

S. Hartnack ◽

S. Essbauer ◽

U. Truyen

Keyword(s):

Vaccinia Virus ◽

Modified Vaccinia Virus Ankara ◽

Virucidal Efficacy

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Truncation of gene F5L partially masks rescue of vaccinia virus strain MVA growth on mammalian cells by restricting plaque size

Journal of General Virology ◽

10.1099/vir.0.058495-0 ◽

2014 ◽

Vol 95 (2) ◽

pp. 466-471 ◽

Cited By ~ 5

Author(s):

Bianca M. Dobson ◽

David C. Tscharke

Keyword(s):

Vaccinia Virus ◽

Mammalian Cells ◽

Serial Passage ◽

Plaque Morphology ◽

Marker Rescue ◽

Modified Vaccinia Virus Ankara ◽

Vacv Strain ◽

Vaccinia Virus Strain

Modified vaccinia virus Ankara (MVA) is a candidate vaccine vector that is severely attenuated due to mutations acquired during several hundred rounds of serial passage in vitro. A previous study used marker rescue to produce a set of MVA recombinants with improved replication on mammalian cells. Here, we extended the characterization of these rescued MVA strains and identified vaccinia virus (VACV) gene F5L as a determinant of plaque morphology but not replication in vitro. F5 joins a growing group of VACV proteins that influence plaque formation more strongly than virus replication and which are disrupted in MVA. These defective genes in MVA confound the interpretation of marker rescue experiments designed to map mutations responsible for the attenuation of this important VACV strain.

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Brief Report: The Virucidal Efficacy of Oral Rinse Components Against SARS-CoV-2 In Vitro

10.1101/2020.11.13.381079 ◽

2020 ◽

Author(s):

Evelina Statkute ◽

Anzelika Rubina ◽

Valerie B O’Donnell ◽

David W. Thomas ◽

Richard J. Stanton

Keyword(s):

Essential Oils ◽

Povidone Iodine ◽

Cetylpyridinium Chloride ◽

Transmission Risk ◽

Log10 Reduction ◽

Live Virus ◽

Oral Rinse ◽

Virucidal Efficacy

AbstractThe ability of widely-available mouthwashes to inactivate SARS-CoV-2 in vitro was tested using a protocol capable of detecting a 5-log10 reduction in infectivity, under conditions mimicking the naso/oropharynx. During a 30 second exposure, two rinses containing cetylpyridinium-chloride and a third with ethanol/ethyl lauroyl arginate eliminated live virus to EN14476 standards (>4-log10 reduction), while others with ethanol/essential oils and povidone-iodine (PVP-I) eliminated virus by 2-3-log10. Chlorhexidine or ethanol alone displayed little or no ability to inactivate virus. Studies are warranted to determine whether these formulations can inactivate virus in the human oropharynx in vivo, and whether this might impact transmission risk.

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Novel Modified Vaccinia Virus Ankara Vector Expressing Anti-apoptotic GeneB13RDelays Apoptosis and Enhances Humoral Responses

Journal of Virology ◽

10.1128/jvi.01648-18 ◽

2018 ◽

Vol 93 (5) ◽

Cited By ~ 2

Author(s):

Lynette S. Chea ◽

Linda S. Wyatt ◽

Sailaja Gangadhara ◽

Bernard Moss ◽

Rama R. Amara

Keyword(s):

Vaccinia Virus ◽

Vaccine Development ◽

Modified Vaccinia Virus Ankara ◽

Immunodeficiency Virus ◽

Antibody Titers ◽

Infected Cells ◽

Induced Apoptosis ◽

Humoral Responses ◽

Antigen Presenting

ABSTRACTModified vaccinia virus Ankara (MVA), an attenuated poxvirus, has been developed as a potential vaccine vector for use against cancer and multiple infectious diseases, including human immunodeficiency virus (HIV). MVA is highly immunogenic and elicits strong cellular and humoral responses in preclinical models and humans. However, there is potential to further enhance the immunogenicity of MVA, as MVA-infected cells undergo rapid apoptosis, leading to faster clearance of recombinant antigens and potentially blunting a greater response. Here, we generated MVA-B13Rby replacing the fragmented181R/182Rgenes of MVA with a functional anti-apoptotic gene,B13R, and confirmed its anti-apoptotic function against chemically induced apoptosisin vitro. In addition, MVA-B13Rshowed a significant delay in induction of apoptosis in muscle cells derived from mice and humans, as well as in plasmacytoid dendritic cells (pDCs) and CD141+DCs from rhesus macaques, compared to the induction of apoptosis in MVA-infected cells. MVA-B13Rexpressing simian immunodeficiency virus (SIV) Gag and Pol and HIV envelope (SHIV) (MVA-B13R/SHIV) produced higher levels of envelope in the supernatants than MVA/SHIV-infected DF-1 cellsin vitro. Immunization of BALB/c mice showed induction of higher levels of envelope-specific antibody-secreting cells and memory B cells, higher IgG antibody titers, and better persistence of antibody titers with MVA-B13R/SHIV than with MVA/SHIV. Gene set enrichment analysis of draining lymph node cells from day 1 after immunization showed negative enrichment for interferon responses in MVA-B13R/SHIV-immunized mice compared to the responses in MVA/SHIV-immunized mice. Taken together, these results demonstrate that restoringB13Rfunctionality in MVA significantly delays MVA-induced apoptosis in muscle and antigen-presenting cellsin vitroand augments vaccine-induced humoral immunity in mice.IMPORTANCEMVA is an attractive viral vector for vaccine development due to its safety and immunogenicity in multiple species and humans even under conditions of immunodeficiency. Here, to further improve the immunogenicity of MVA, we developed a novel vector, MVA-B13R, by replacing the fragmented anti-apoptotic genes181R/182Rwith a functional version derived from vaccinia virus,B13R. Our results show that MVA-B13Rsignificantly delays apoptosis in antigen-presenting cells and muscle cellsin vitroand augments vaccine-induced humoral immunity in mice, leading to the development of a novel vector for vaccine development against infectious diseases and cancer.

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OA02-06 LB. Recombinant modified Vaccinia virus ankara expressing HIV-1 genes activates NK subset capable of controlling HIN infection in vitro

Retrovirology ◽

10.1186/1742-4690-6-s3-o18 ◽

2009 ◽

Vol 6 (Suppl 3) ◽

pp. O18 ◽

Cited By ~ 2

Author(s):

J Cummings ◽

V Arnold ◽

K Yarbrough ◽

C Didier ◽

Y Levy ◽

...

Keyword(s):

Vaccinia Virus ◽

Modified Vaccinia Virus Ankara ◽

Hiv 1

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Vaccinia Virus-Mediated Inhibition of Type I Interferon Responses Is a Multifactorial Process Involving the Soluble Type I Interferon Receptor B18 and Intracellular Components

Journal of Virology ◽

10.1128/jvi.01617-08 ◽

2008 ◽

Vol 83 (4) ◽

pp. 1563-1571 ◽

Cited By ~ 50

Author(s):

Zoe Waibler ◽

Martina Anzaghe ◽

Theresa Frenz ◽

Astrid Schwantes ◽

Christopher Pöhlmann ◽

...

Keyword(s):

Vaccinia Virus ◽

Type I Interferon ◽

Poly I:C ◽

Host Responses ◽

Type I ◽

Immune Modulators ◽

Modified Vaccinia Virus Ankara ◽

Multistep Process ◽

Interferon Responses

ABSTRACT Poxviruses such as virulent vaccinia virus (VACV) strain Western Reserve encode a broad range of immune modulators that interfere with host responses to infection. Upon more than 570 in vitro passages in chicken embryo fibroblasts (CEF), chorioallantois VACV Ankara (CVA) accumulated mutations that resulted in highly attenuated modified vaccinia virus Ankara (MVA). MVA infection of mice and of dendritic cells (DC) induced significant type I interferon (IFN) responses, whereas infection with VACV alone or in combination with MVA did not. These results implied that VACV expressed an IFN inhibitor(s) that was functionally deleted in MVA. To further characterize the IFN inhibitor(s), infection experiments were carried out with CVA strains isolated after 152 (CVA152) and 386 CEF passages (CVA386). Interestingly, neither CVA152 nor CVA386 induced IFN-α, whereas the latter variant did induce IFN-β. This pattern suggested a consecutive loss of inhibitors during MVA attenuation. Similar to supernatants of VACV- and CVA152-infected DC cultures, recombinantly expressed soluble IFN decoy receptor B18, which is encoded in the VACV genome, inhibited MVA-induced IFN-α but not IFN-β. In the same direction, a B18R-deficient VACV variant triggered only IFN-α, confirming B18 as the soluble IFN-α inhibitor. Interestingly, VACV infection inhibited IFN responses induced by a multitude of different stimuli, including oligodeoxynucleotides containing CpG motifs, poly(I:C), and vesicular stomatitis virus. Collectively, the data presented show that VACV-mediated IFN inhibition is a multistep process involving secreted factors such as B18 plus intracellular components that cooperate to efficiently shut off systemic IFN-α and IFN-β responses.

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