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Emerging Microbes & Infections Dec 2023Current unprecedented mpox outbreaks in non-endemic regions represent a global public health concern. Although two live-attenuated vaccinia virus (VACV)-based vaccines...
Current unprecedented mpox outbreaks in non-endemic regions represent a global public health concern. Although two live-attenuated vaccinia virus (VACV)-based vaccines have been urgently approved for people at high risk for mpox, a safer and more effective vaccine that can be available for the general public is desperately needed. By utilizing a simplified manufacturing strategy of mixing DNA plasmids before transcription, we developed two multi-antigen mRNA vaccine candidates, which encode four (M1, A29, B6, A35, termed as Rmix4) or six (M1, H3, A29, E8, B6, A35, termed as Rmix6) mpox virus antigens. We demonstrated that those mpox multi-antigen mRNA vaccine candidates elicited similar potent cross-neutralizing immune responses against VACV, and compared to Rmix4, Rmix6 elicited significantly stronger cellular immune responses. Moreover, immunization with both vaccine candidates protected mice from the lethal VACV challenge. Investigation of B-cell receptor (BCR) repertoire elicited by mpox individual antigen demonstrated that the M1 antigen efficiently induced neutralizing antibody responses, and all neutralizing antibodies among the top 20 frequent antibodies appeared to target the same conformational epitope as 7D11, revealing potential vulnerability to viral immune evasion. Our findings suggest that Rmix4 and Rmix6 from a simplified manufacturing process are promising candidates to combat mpox.
Topics: Animals; Mice; Antibodies, Viral; Orthopoxvirus; Viral Envelope Proteins; Mpox (monkeypox); Antibodies, Neutralizing; Vaccinia virus
PubMed: 37070521
DOI: 10.1080/22221751.2023.2204151 -
Indian Journal of Pharmacology Mar 2024The virus known as monkeypox is the source of the zoonotic disease monkeypox, which was historically widespread in Central Africa and West Africa. The cases of monkeypox... (Review)
Review
The virus known as monkeypox is the source of the zoonotic disease monkeypox, which was historically widespread in Central Africa and West Africa. The cases of monkeypox in humans are uncommon outside of West and Central Africa, but copious nonendemic nations outside of Africa have recently confirmed cases. People when interact with diseased animals, then, they may inadvertently contact monkeypox. There are two drugs in the market: brincidofovir and tecovirimat and both of these drugs are permitted for the cure of monkeypox by the US Food and Drug Administration. The present review summarizes the various parameters of monkeypox in context with transmission, signs and symptoms, histopathological and etiological changes, and possible treatment. Monkeypox is clinically similar to that of smallpox infection but epidemiologically, these two are different, the present study also signifies the main differences and similarities of monkeypox to that of other infectious diseases. As it is an emerging disease, it is important to know about the various factors related to monkeypox so as to control it on a very early stage of transmission.
Topics: Mpox (monkeypox); Humans; Animals; Antiviral Agents; Communicable Diseases, Emerging; Cytosine; Monkeypox virus; Isoindoles; Organothiophosphorus Compounds; Organophosphonates; Benzamides; Phthalimides
PubMed: 38687317
DOI: 10.4103/ijp.ijp_156_23 -
Virulence Dec 2023Monkeypox (Mpox) was mostly limited to Central and Western Africa, but recently it has been reported globally. The current review presents an update on the virus,... (Review)
Review
Monkeypox (Mpox) was mostly limited to Central and Western Africa, but recently it has been reported globally. The current review presents an update on the virus, including ecology and evolution, possible drivers of transmission, clinical features and management, knowledge gaps, and research priorities to reduce the disease transmission. The origin, reservoir(s) and the sylvatic cycle of the virus in the natural ecosystem are yet to be confirmed. Humans acquire the infection through contact with infected animals, humans, and natural hosts. The major drivers of disease transmission include trapping, hunting, bushmeat consumption, animal trade, and travel to endemic countries. However, in the 2022 epidemic, the majority of the infected humans in non-endemic countries had a history of direct contact with clinical or asymptomatic persons through sexual activity. The prevention and control strategies should include deterring misinformation and stigma, promoting appropriate social and behavioural changes, including healthy life practices, instituting contact tracing and management, and using the smallpox vaccine for high-risk people. Additionally, longer-term preparedness should be emphasized using the One Health approach, such as systems strengthening, surveillance and detection of the virus across regions, early case detection, and integrating measures to mitigate the socio-economic effects of outbreaks.
Topics: Animals; Humans; Mpox (monkeypox); Virulence; Ecosystem; Monkeypox virus; Ecology; Disease Outbreaks
PubMed: 36864002
DOI: 10.1080/21505594.2023.2186357 -
Microbiology Spectrum Aug 2023Monkeypox virus (MPXV) infections in humans have historically been restricted to regions of endemicity in Africa. However, in 2022, an alarming number of MPXV cases were...
Monkeypox virus (MPXV) infections in humans have historically been restricted to regions of endemicity in Africa. However, in 2022, an alarming number of MPXV cases were reported globally, with evidence of person-to-person transmission. Because of this, the World Health Organization (WHO) declared the MPXV outbreak a public health emergency of international concern. The supply of MPXV vaccines is limited, and only two antivirals, tecovirimat and brincidofovir, approved by the U.S. Food and Drug Administration (FDA) for the treatment of smallpox, are currently available for the treatment of MPXV infection. Here, we evaluated 19 compounds previously shown to inhibit different RNA viruses for their ability to inhibit orthopoxvirus infections. We first used recombinant vaccinia virus (rVACV) expressing fluorescence (mScarlet or green fluorescent protein [GFP]) and luciferase (Nluc) reporter genes to identify compounds with antiorthopoxvirus activity. Seven compounds from the ReFRAME library (antimycin A, mycophenolic acid, AVN-944, pyrazofurin, mycophenolate mofetil, azaribine, and brequinar) and six compounds from the NPC library (buparvaquone, valinomycin, narasin, monensin, rotenone, and mubritinib) showed inhibitory activity against rVACV. Notably, the anti-VACV activity of some of the compounds in the ReFRAME library (antimycin A, mycophenolic acid, AVN-944, mycophenolate mofetil, and brequinar) and all the compounds from the NPC library (buparvaquone, valinomycin, narasin, monensin, rotenone, and mubritinib) were confirmed with MPXV, demonstrating their inhibitory activity against two orthopoxviruses. Despite the eradication of smallpox, some orthopoxviruses remain important human pathogens, as exemplified by the recent 2022 monkeypox virus (MPXV) outbreak. Although smallpox vaccines are effective against MPXV, access to those vaccines is limited. In addition, current antiviral treatment against MPXV infections is limited to the use of the FDA-approved drugs tecovirimat and brincidofovir. Thus, there is an urgent need to identify novel antivirals for the treatment of MPXV infection and other potentially zoonotic orthopoxvirus infections. Here, we show that 13 compounds, derived from two different libraries, previously found to inhibit several RNA viruses, also inhibit VACV. Notably, 11 compounds also displayed inhibitory activity against MPXV.
Topics: Humans; Mpox (monkeypox); Mycophenolic Acid; Smallpox; Antimycin A; Monensin; Rotenone; Valinomycin; Monkeypox virus; Antiviral Agents
PubMed: 37278625
DOI: 10.1128/spectrum.04745-22 -
Archives of Virology Aug 2023Mpox (formerly monkeypox) is a zoonotic disease caused by monkeypox virus (MPXV), which, like smallpox, is characterised by skin rashes. While the world is currently... (Review)
Review
Mpox (formerly monkeypox) is a zoonotic disease caused by monkeypox virus (MPXV), which, like smallpox, is characterised by skin rashes. While the world is currently grappling with the coronavirus disease 2019 pandemic, the appearance of MPXV has presented a global threat and raised concerns worldwide. Since May 2022, MPXV has spread rapidly in non-endemic mpox areas. As of 27 June 2023, the virus has spread to more than 112 countries and regions, with over 88,060 laboratory-confirmed cases and 147 deaths. Thus, measures to control the mpox epidemic are urgently needed. As the principal methods for identifying and monitoring mpox, laboratory detection techniques play an important role in mpox diagnosis. This review summarises the currently-used laboratory techniques for MPXV detection, discusses progress in improving these methods, and compares the benefits and limitations of various diagnostic detection methods. Currently, nucleic acid amplification tests, such as the polymerase chain reaction, are the most commonly used. Immunological methods have also been applied to diagnose the disease, which can help us discover new features of MPXV, improve diagnostic accuracy, track epidemic trends, and guide future prevention and control strategies, which are also vital for controlling mpox epidemics. This review provides a resource for the scientific community and should stimulate more research and development in alternative diagnostics to be applied to this and future public health crises.
Topics: Animals; COVID-19; Mpox (monkeypox); Pandemics; Polymerase Chain Reaction; Zoonoses
PubMed: 37543543
DOI: 10.1007/s00705-023-05848-w -
Nature Communications May 2024The Modified Vaccinia Ankara vaccine developed by Bavarian Nordic (MVA-BN) was widely deployed to prevent mpox during the 2022 global outbreak. This vaccine was... (Meta-Analysis)
Meta-Analysis
The Modified Vaccinia Ankara vaccine developed by Bavarian Nordic (MVA-BN) was widely deployed to prevent mpox during the 2022 global outbreak. This vaccine was initially approved for mpox based on its reported immunogenicity (from phase I/II trials) and effectiveness in animal models, rather than evidence of clinical efficacy. However, no validated correlate of protection after vaccination has been identified. Here we performed a systematic search and meta-analysis of the available data to test whether vaccinia-binding ELISA endpoint titer is predictive of vaccine effectiveness against mpox. We observe a significant correlation between vaccine effectiveness and vaccinia-binding antibody titers, consistent with the existing assumption that antibody levels may be a correlate of protection. Combining this data with analysis of antibody kinetics after vaccination, we predict the durability of protection after vaccination and the impact of dose spacing. We find that delaying the second dose of MVA-BN vaccination will provide more durable protection and may be optimal in an outbreak with limited vaccine stock. Although further work is required to validate this correlate, this study provides a quantitative evidence-based approach for using antibody measurements to predict the effectiveness of mpox vaccination.
Topics: Animals; Humans; Antibodies, Viral; Enzyme-Linked Immunosorbent Assay; Smallpox Vaccine; Vaccination; Vaccine Efficacy; Vaccinia; Monkeypox virus
PubMed: 38719852
DOI: 10.1038/s41467-024-48180-w -
Viruses Aug 2023Lumpy skin disease (LSD), a current global concern, causes economic devastation in livestock industries, with cattle and water buffalo reported to have higher morbidity... (Review)
Review
Lumpy skin disease (LSD), a current global concern, causes economic devastation in livestock industries, with cattle and water buffalo reported to have higher morbidity and lower mortality rates. LSD is caused by lumpy skin disease virus (LSDV), a member of the Poxviridae family. It is an enzootic, rapidly explorative and sometimes fatal infection, characterized by multiple raised nodules on the skin of infected animals. It was first reported in Zambia in 1929 and is considered endemic in Africa south of the Sahara desert. It has gradually spread beyond Africa into the Middle East, with periodic occurrences in Asian and East European countries. Recently, it has been spreading in most Asian countries including far East Asia and threatens incursion to LSD-free countries. Rapid and accurate diagnostic capabilities, virus identification, vaccine development, vector control, regional and international collaborations and effective biosecurity policies are important for the control, prevention, and eradication of LSD infections. This review critically evaluates the global burden of LSD, the chronological historical outbreaks of LSD, and future directions for collaborative global actions.
Topics: Animals; Cattle; Humans; Lumpy Skin Disease; Disease Outbreaks; Africa, Northern; Asia; Buffaloes; Zambia
PubMed: 37766268
DOI: 10.3390/v15091861 -
Enfermedades Infecciosas Y... Dec 2023Monkeypox is a zoonosis that is spread mainly through direct contact with fluids and skin lesions of infected people with vesicles still active. Although the virus was... (Review)
Review
Monkeypox is a zoonosis that is spread mainly through direct contact with fluids and skin lesions of infected people with vesicles still active. Although the virus was isolated for the first time in 1958 and the first human case was identified in a child in 1970, in the Democratic Republic of the Congo, the disease has progressively increased its incidence in Africa reaching in May 2022 sustained transmission outside this continent. As it is a newly introduced virus in our health system, it is necessary to learn the epidemiological pattern in a different environment from that of traditionally endemic areas and to know the available antiviral treatments, as well as the prophylactic measures that could be considered, knowing that as a virus emerging in our regions, scientific evidence is still limited. There are antivirals that have been shown, in animal models, to effectively combat the disease with very good clinical tolerance. This disease has also forced us to review the characteristics of smallpox vaccines, because they have shown a protective effect against monkeypox. For this reason, it is important to have a document that compiles all the scientific information published in this regard.
Topics: Child; Animals; Humans; Mpox (monkeypox); Monkeypox virus; Smallpox Vaccine; Africa; Incidence
PubMed: 36624034
DOI: 10.1016/j.eimce.2022.12.010 -
Journal of Infection and Public Health Aug 2023The end of smallpox in 1980 and the subsequent stopping of vaccination against smallpox was followed by the emergence of monkeypox (mpox), a viral disease of animal... (Review)
Review
BACKGROUND
The end of smallpox in 1980 and the subsequent stopping of vaccination against smallpox was followed by the emergence of monkeypox (mpox), a viral disease of animal origin, meaning that it is transmitted from animal to human. The symptoms of mpox are similar to smallpox, except that they are less severe in terms of clinical features. In the case of public health, the mpox virus is one of the most important orthopoxviruses (such as variola, cowpox, and vaccinia) that come from the family Poxviridae. Mpox occurs mostly in central Africa and sometimes in tropical rainforests or some urban areas. Also, there are threats other than COVID-19, that must be addressed and prevented from spreading, as there has been an outbreak of mpox cases since May 7, 2022, throughout the USA, Europe, Australia, and part of Africa.
OBJECTIVES
In this review, we will discuss mpox between the past, the present and during the COVID-19 pandemic. Also, it offers an updated summary of the taxonomy, etiology, transmission, and epidemiology of mpox illness. In addition, the current review aims to highlight the importance of emerging pandemics in the same era such as mpox and COVID-19.
METHODS
A literature search was done for the study using online sources like PubMed and Google Scholar. Publications in English were included. Data for study variables were extracted. After the duplicate articles were eliminated, full-text screening was performed on the papers' titles and abstracts.
RESULTS
The evaluation included a series documenting mpox virus outbreaks, and both prospective and retrospectiveinvestigations.
CONCLUSIONS
monkeypox is a viral disease caused by the monkeypox virus (MPXV), which is primarily found in central and western Africa. The disease is transmitted from animals to humans and presents symptoms similar to those of smallpox, including fever, headache, muscle aches, and a rash. Monkeypox can lead to complications such as secondary integument infection, bronchopneumonia, sepsis, and encephalitis, as well as corneal infection that can result in blindness. There is no specific clinically proven treatment for monkeypox, and treatment is primarily supportive. However, antiviral drugs and vaccines are available for cross-protection against the virus, and strict infection control measures and vaccination of close contacts of affected individuals can help prevent and control outbreaks.
Topics: Animals; Humans; Mpox (monkeypox); Monkeypox virus; Smallpox; COVID-19; Pandemics; Prospective Studies
PubMed: 37269693
DOI: 10.1016/j.jiph.2023.05.013 -
Journal of Molecular Biology Aug 2023Although one member of the poxvirus family, variola virus, has caused one of the most devastating human infections worldwide, smallpox, the knowledge gained over the... (Review)
Review
Although one member of the poxvirus family, variola virus, has caused one of the most devastating human infections worldwide, smallpox, the knowledge gained over the last 30 years on the molecular, virological and immunological mechanisms of these viruses has allowed the use of members of this family as vectors for the generation of recombinant vaccines against numerous pathogens. In this review, we cover different aspects of the history and biology of poxviruses with emphasis on their application as vaccines, from first- to fourth-generation, against smallpox, monkeypox, emerging viral diseases highlighted by the World Health Organization (COVID-19, Crimean-Congo haemorrhagic fever, Ebola and Marburg virus diseases, Lassa fever, Middle East respiratory syndrome and severe acute respiratory syndrome, Nipah and other henipaviral diseases, Rift Valley fever and Zika), as well as against one of the most concerning prevalent virus, the Human Immunodeficiency Virus, the causative agent of Acquired Immunodeficiency Syndrome. We discuss the implications in human health of the 2022 monkeypox epidemic affecting many countries, and the rapid prophylactic and therapeutic measures adopted to control virus dissemination within the human population. We also describe the preclinical and clinical evaluation of the Modified Vaccinia virus Ankara and New York vaccinia virus poxviral strains expressing heterologous antigens from the viral diseases listed above. Finally, we report different approaches to improve the immunogenicity and efficacy of poxvirus-based vaccine candidates, such as deletion of immunomodulatory genes, insertion of host-range genes and enhanced transcription of foreign genes through modified viral promoters. Some future prospects are also highlighted.
Topics: Animals; Humans; Communicable Diseases, Emerging; COVID-19; Genetic Vectors; Mpox (monkeypox); Poxviridae; Smallpox; Vaccines, Attenuated; Vaccinia virus; Viral Vaccines; Virus Diseases; Zika Virus; Zika Virus Infection
PubMed: 37301278
DOI: 10.1016/j.jmb.2023.168173