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Frontiers in Immunology 2024Modified vaccinia virus Ankara (MVA) has been widely tested in clinical trials as recombinant vector vaccine against infectious diseases and cancers in humans and...
Whole genome sequencing of recombinant viruses obtained from co-infection and superinfection of Vero cells with modified vaccinia virus ankara vectored influenza vaccine and a naturally occurring cowpox virus.
Modified vaccinia virus Ankara (MVA) has been widely tested in clinical trials as recombinant vector vaccine against infectious diseases and cancers in humans and animals. However, one biosafety concern about the use of MVA vectored vaccine is the potential for MVA to recombine with naturally occurring orthopoxviruses in cells and hosts in which it multiplies poorly and, therefore, producing viruses with mosaic genomes with altered genetic and phenotypic properties. We previously conducted co-infection and superinfection experiments with MVA vectored influenza vaccine (MVA-HANP) and a feline Cowpox virus (CPXV-No-F1) in Vero cells (that were semi-permissive to MVA infection) and showed that recombination occurred in both co-infected and superinfected cells. In this study, we selected the putative recombinant viruses and performed genomic characterization of these viruses. Some putative recombinant viruses displayed plaque morphology distinct of that of the parental viruses. Our analysis demonstrated that they had mosaic genomes of different lengths. The recombinant viruses, with a genome more similar to MVA-HANP (>50%), rescued deleted and/or fragmented genes in MVA and gained new host ranges genes. Our analysis also revealed that some MVA-HANP contained a partially deleted transgene expression cassette and one recombinant virus contained part of the transgene expression cassette similar to that incomplete MVA-HANP. The recombination in co-infected and superinfected Vero cells resulted in recombinant viruses with unpredictable biological and genetic properties as well as recovery of delete/fragmented genes in MVA and transfer of the transgene into replication competent CPXV. These results are relevant to hazard characterization and risk assessment of MVA vectored biologicals.
Topics: Chlorocebus aethiops; Animals; Cats; Humans; Influenza Vaccines; Cowpox virus; Vero Cells; Coinfection; Superinfection; Vaccinia virus; Vaccines, Synthetic; Whole Genome Sequencing
PubMed: 38633245
DOI: 10.3389/fimmu.2024.1277447 -
Proceedings (Baylor University. Medical... 2024Mpox is a double-stranded DNA virus of the Orthopoxvirus genus related to smallpox virus endemic to Africa with more than 16,000 cases reported in nonendemic countries...
Mpox is a double-stranded DNA virus of the Orthopoxvirus genus related to smallpox virus endemic to Africa with more than 16,000 cases reported in nonendemic countries in 2022. Classically associated with adult men who have sex with men (MSM), Mpox was once labeled a public health emergency by the World Health Organization as concerning to the general population. Supraglottitis is a rare complication of Mpox that is underreported in the literature and presents a potential airway emergency. Prompt identification is necessary for preventing airway decompensation.
PubMed: 38628346
DOI: 10.1080/08998280.2024.2314408 -
Nature Communications Apr 2024The emerging monkeypox virus (MPXV) has raised global health concern, thereby highlighting the need for rapid, sensitive, and easy-to-use diagnostics. Here, we develop a...
The emerging monkeypox virus (MPXV) has raised global health concern, thereby highlighting the need for rapid, sensitive, and easy-to-use diagnostics. Here, we develop a single-step CRISPR-based diagnostic platform, termed SCOPE (Streamlined CRISPR On Pod Evaluation platform), for field-deployable ultrasensitive detection of MPXV in resource-limited settings. The viral nucleic acids are rapidly released from the rash fluid swab, oral swab, saliva, and urine samples in 2 min via a streamlined viral lysis protocol, followed by a 10-min single-step recombinase polymerase amplification (RPA)-CRISPR/Cas13a reaction. A pod-shaped vest-pocket analysis device achieves the whole process for reaction execution, signal acquisition, and result interpretation. SCOPE can detect as low as 0.5 copies/µL (2.5 copies/reaction) of MPXV within 15 min from the sample input to the answer. We validate the developed assay on 102 clinical samples from male patients / volunteers, and the testing results are 100% concordant with the real-time PCR. SCOPE achieves a single-molecular level sensitivity in minutes with a simplified procedure performed on a miniaturized wireless device, which is expected to spur substantial progress to enable the practice application of CRISPR-based diagnostics techniques in a point-of-care setting.
Topics: Humans; Male; Monkeypox virus; Biological Assay; Cell Death; Exanthema; Nucleotidyltransferases; Nucleic Acid Amplification Techniques; Sensitivity and Specificity; CRISPR-Cas Systems; Recombinases
PubMed: 38627378
DOI: 10.1038/s41467-024-47518-8 -
Nature Communications Apr 2024The eradication of smallpox was officially declared by the WHO in 1980, leading to discontinuation of the vaccination campaign against the virus. Consequently, immunity...
The eradication of smallpox was officially declared by the WHO in 1980, leading to discontinuation of the vaccination campaign against the virus. Consequently, immunity against smallpox and related orthopoxviruses like Monkeypox virus gradually declines, highlighting the need for efficient countermeasures not only for the prevention, but also for the treatment of already exposed individuals. We have recently developed human-like monoclonal antibodies (mAbs) from vaccinia virus-immunized non-human primates. Two mAbs, MV33 and EV42, targeting the two infectious forms of the virus, were selected for in vivo evaluation, based on their in vitro neutralization potency. A single dose of either MV33 or EV42 administered three days post-infection (dpi) to BALB/c female mice provides full protection against lethal ectromelia virus challenge. Importantly, a combination of both mAbs confers full protection even when provided five dpi. Whole-body bioimaging and viral load analysis reveal that combination of the two mAbs allows for faster and more efficient clearance of the virus from target organs compared to either MV33 or EV42 separately. The combined mAbs treatment further confers post-exposure protection against the currently circulating Monkeypox virus in Cast/EiJ female mice, highlighting their therapeutic potential against other orthopoxviruses.
Topics: Humans; Female; Animals; Mice; Smallpox; Antibodies, Monoclonal; Poxviridae Infections; Vaccinia; Vaccinia virus; Orthopoxvirus; Antibodies, Viral
PubMed: 38627363
DOI: 10.1038/s41467-024-47328-y -
Journal of Infection and Public Health Jun 2024After the eradication of smallpox, there have been no specific public health measures for any Orthopoxviruses (OPXVs). Therefore, it is necessary to countermeasure OPXV...
BACKGROUND
After the eradication of smallpox, there have been no specific public health measures for any Orthopoxviruses (OPXVs). Therefore, it is necessary to countermeasure OPXV infections after Mpox (formerly monkeypox) occurrences, such as the latest global outbreak in 2022-2023. This study aimed to provide crucial insights for the development of effective public health policy making against mpox in populations residing in regions where the virus is not prevalent.
METHODS
This study used enzyme-linked immunosorbent assays (ELISA) to examine smallpox and mpox antibodies in Koreans with three different age groups. We analyzed 56 sera obtained from a tertiary care hospital in South Korea between September 2022 and April 2023. Plasma levels of antibodies against the viral proteins of smallpox (variola cytokine response-modifying protein B) and MPXV (A29) were measured using enzyme-linked immunosorbent assays.
RESULTS
Plasma samples from participants in their early 40 s and older exhibited higher reactivity to viral antigens than those from younger participants. Furthermore, there was a strong positive correlation in antibody positivity for the two different viruses across the sera.
CONCLUSIONS
The presence of low antibody levels in participants ˂40 years may hinder their ability to defend against OPXV. Therefore, it is imperative to implement effective public health measures to mitigate the transmission of OPXV within the community. These findings serve as fundamental information for devising strategies to combat mpox efficiently, particularly in regions where the virus is not prevalent.
Topics: Humans; Adult; Antibodies, Viral; Republic of Korea; Male; Middle Aged; Young Adult; Enzyme-Linked Immunosorbent Assay; Female; Orthopoxvirus; Age Factors; Public Health; Aged; Adolescent; Antibody Formation; Smallpox; Poxviridae Infections; Mpox (monkeypox)
PubMed: 38608456
DOI: 10.1016/j.jiph.2024.04.002 -
PloS One 2024Timely case notifications following the introduction of an uncommon pathogen, such as mpox, are critical for understanding disease transmission and for developing and...
Deployment of the National Notifiable Diseases Surveillance System during the 2022-23 mpox outbreak in the United States-Opportunities and challenges with case notifications during public health emergencies.
Timely case notifications following the introduction of an uncommon pathogen, such as mpox, are critical for understanding disease transmission and for developing and implementing effective mitigation strategies. When Massachusetts public health officials notified the Centers for Disease Control and Prevention (CDC) about a confirmed orthopoxvirus case on May 17, 2023, which was later confirmed as mpox at CDC, mpox was not a nationally notifiable disease. Because existing processes for new data collections through the National Notifiable Disease Surveillance System were not well suited for implementation during emergency responses at the time of the mpox outbreak, several interim notification approaches were established to capture case data. These interim approaches were successful in generating daily case counts, monitoring disease transmission, and identifying high-risk populations. However, the approaches also required several data collection approvals by the federal government and the Council for State and Territorial Epidemiologists, the use of four different case report forms, and the establishment of complex data management and validation processes involving data element mapping and record-level de-duplication steps. We summarize lessons learned from these interim approaches to inform and improve case notifications during future outbreaks. These lessons reinforce CDC's Data Modernization Initiative to work in close collaboration with state, territorial, and local public health departments to strengthen case-based surveillance prior to the next public health emergency.
Topics: United States; Humans; Public Health; Emergencies; Mpox (monkeypox); Disease Outbreaks; Massachusetts; Population Surveillance
PubMed: 38603766
DOI: 10.1371/journal.pone.0300175 -
Emerging Microbes & Infections Dec 2024(MPXV) infection confirmation needs reliable polymerase chain reaction (PCR) assays; in addition, viral clade attribution is a key factor in containment measures,...
(MPXV) infection confirmation needs reliable polymerase chain reaction (PCR) assays; in addition, viral clade attribution is a key factor in containment measures, considering a more severe syndrome in clade I and the possibility of simultaneous circulation. This study evaluates the performance of all-in-one STANDARD M10 MPX/OPX (SD BIOSENSOR, South Korea - M10). Frozen samples from 205 subjects were selected and stratified according to routine test results (RealStar® Orthopoxvirus PCR Kit 1.0, Altona DIAGNOTICS, Germany - RS; RS-1): in detail, 100 negative skin lesions (SL) and 200 positive samples at the variable stage of infection were analysed. Positive samples were retested with RS (RS-2). Positive and Negative Percent Agreements (PPA, NPA) were calculated. The median (IQR) values of RS and M10 (OPXV target) assays were highly similar. The PPA of M10 compared to RS-1 was 89.5% considering system interpretation, and 96.0% when the operator classified results as positive if any target was detected; NPA was 100%. Comparing the RS-2 run and M10, an overall concordance of 95.3% between assays was found; however, considering operator interpretation, M10 returned more positive results than RS-2. The occurrence of False-Negative results was likely associated with the influence of thawing on low viral concentration; no False-Positive tests were observed. All samples collected at the time of Mpox diagnosis were positive and M10 correctly attributed the clade (West-Africa/II). The M10 MPX/OPX assay demonstrated high reliability in confirming MPXV infection and clade attribution.
Topics: Humans; Monkeypox virus; Mpox (monkeypox); Reproducibility of Results; DNA, Viral; Africa, Western
PubMed: 38572513
DOI: 10.1080/22221751.2024.2337666 -
Cell Reports Apr 2024Seo et al. shed light on virus-host interactions as they reveal how poxvirus A51R stabilizes microtubules in infected cells, which impacts vaccinia virus virulence in...
Seo et al. shed light on virus-host interactions as they reveal how poxvirus A51R stabilizes microtubules in infected cells, which impacts vaccinia virus virulence in mice by potentially inhibiting reactive-oxygen-species-dependent antiviral responses in macrophages.
Topics: Vaccinia virus; Virulence; Microtubules; Viral Proteins; Host-Parasite Interactions; Humans; Animals; Mice
PubMed: 38564336
DOI: 10.1016/j.celrep.2024.114050 -
Acta Medica Indonesiana Jan 2024Mpox is caused by the Monkeypox virus, which belongs to the Orthopoxvirus genus and Poxviridae family. The Monkeypox virus was first identified as a cause of disease in...
Mpox is caused by the Monkeypox virus, which belongs to the Orthopoxvirus genus and Poxviridae family. The Monkeypox virus was first identified as a cause of disease in humans in the 1970s in the Democratic Republic of the Congo. Mpox was considered endemic in several African countries. A global outbreak of Mpox was first recognized in Europe in May 2022 and was declared a public health emergency of international concern on July 23, 2022. The first reported Mpox case in Indonesia was in October 2022 which was identified as an imported case, there were no new confirmed Mpox cases until 13 October 2023. Since then there were 72 cases of confirmed Mpox cases in Indonesia by the end of 2023, distributed across 6 provinces, mostly in the Java island.We present two different spectrums of Mpox skin lesions in patients living with HIV, with a positive polymerase chain reaction test for Mpox. The first patient is a 48-year-old male, who developed a maculopapular lesion, that was initially noticed on the face, the lesions were then spread to the back and hand. He identifies as men who have sex with men and living with HIV for the past 18 years. There were no lesions on the genitalia or mucosa. The second patient is a 28-year-old male, the initial symptom was fever, followed by skin lesions after around 1 week of fever. The lesion initially appears as pustules on the face and then spreads throughout the whole body, the lesions also grow larger and become pseudo-pustules and ulcers. There were also mucosal involvements in the mouth, making oral intake difficult. This patient also identified as men who have sex with men with multiple partners, HIV status was not known at the initial presentation. HIV screening was done with positive results.
Topics: Male; Humans; Middle Aged; Adult; Homosexuality, Male; Mpox (monkeypox); Sexual and Gender Minorities; Disease Outbreaks; HIV Infections
PubMed: 38561878
DOI: No ID Found -
Frontiers in Immunology 2024In recent years, oncolytic viruses have emerged as promising agents for treating various cancers. An oncolytic virus is a non-pathogenic virus that, due to genetic... (Review)
Review
In recent years, oncolytic viruses have emerged as promising agents for treating various cancers. An oncolytic virus is a non-pathogenic virus that, due to genetic manipulation, tends to replicate in and cause lysis of cancerous cells while leaving healthy cells unaffected. Among these viruses, vaccinia virus is an attractive platform for use as an oncolytic platform due to its 190 Kb genome with a high capacity for encoding therapeutic payloads. Combining oncolytic VV therapy with other conventional cancer treatments has been shown to be synergistic and more effective than monotherapies. Additionally, OVV can be used as a vector to deliver therapeutic payloads, alone or in combination with other treatments, to increase overall efficacy. Here, we present a comprehensive analysis of preclinical and clinical studies that have evaluated the efficacy of oncolytic vaccinia viruses in cancer immunotherapy. We discuss the outcomes of these studies, including tumor regression rates, overall survival benefits, and long-term responses. Moreover, we provide insights into the challenges and limitations associated with oncolytic vaccinia virus- based therapies, including immune evasion mechanisms, potential toxicities, and the development of resistance.
Topics: Humans; Oncolytic Viruses; Vaccinia virus; Oncolytic Virotherapy; Neoplasms; Immunotherapy
PubMed: 38558795
DOI: 10.3389/fimmu.2024.1272351