-
Nature Communications May 2024The recent outbreak of mpox epidemic, caused by monkeypox virus (MPXV), poses a new threat to global public health. Here, we initially assessed the preexisting antibody...
The recent outbreak of mpox epidemic, caused by monkeypox virus (MPXV), poses a new threat to global public health. Here, we initially assessed the preexisting antibody level to the MPXV B6 protein in vaccinia vaccinees born before the end of the immunization program and then identified two monoclonal antibodies (MAbs), hMB621 and hMB668, targeting distinct epitopes on B6, from one vaccinee. Binding assays demonstrate that both MAbs exhibit broad binding abilities to B6 and its orthologs in vaccinia (VACV), variola (VARV) and cowpox viruses (CPXV). Neutralizing assays reveal that the two MAbs showed potent neutralization against VACV. Animal experiments using a BALB/c female mouse model indicate that the two MAbs showed effective protection against VACV via intraperitoneal injection. Additionally, we determined the complex structure of B6 and hMB668, revealing the structural feature of B6 and the epitope of hMB668. Collectively, our study provides two promising antibody candidates for the treatment of orthopoxvirus infections, including mpox.
Topics: Animals; Mice, Inbred BALB C; Humans; Female; Antibodies, Neutralizing; Antibodies, Viral; Mice; Antibodies, Monoclonal; Epitopes; Monkeypox virus; Poxviridae Infections; Vaccinia virus; Orthopoxvirus; Mpox (monkeypox)
PubMed: 38821921
DOI: 10.1038/s41467-024-48312-2 -
Heart & Lung : the Journal of Critical... 2023Monkeypox (Mpox) is a zoonotic DNA virus related to the orthopoxvirus family that causes also smallpox infection. (Review)
Review
BACKGROUND
Monkeypox (Mpox) is a zoonotic DNA virus related to the orthopoxvirus family that causes also smallpox infection.
OBJECTIVES
In this paper, we aimed to study the cardiovascular manifestations of Mpox.
METHOD
A literature databases search was conducted on 20th October 2022 and limited to 2022 (the new outbreak) to collect all the relevant papers that discussed cardiovascular manifestations in Mpox.
RESULTS
The literature included 6 cases of myocarditis, one case of pericarditis, one case of myopericarditis and one case of atrial fibrillation. Of total 6 cases with completed data, ECG results and troponin levels were abnormal in 5 cases while only three cases had abnormal ECHO and CMR results. In the four cases who undergone chest X-rays, only one patient had non-specific retro-cardiac opacities. All patients (9 cases) recovered well from their cardiovascular manifestations with no deaths and only 3 of them required ICU admission.
CONCLUSION
With the limited reported cases, we recommend performing cardiovascular examinations -in particular ECG and troponin levels- in order to exclude cardiovascular insult in patients with suspected Mpox -cardiovascular involvement. However, in our series the infection was mild in most patients with no mortality.
Topics: Humans; Monkeypox virus; Mpox (monkeypox); Disease Outbreaks; Heart; Myocarditis
PubMed: 36739643
DOI: 10.1016/j.hrtlng.2023.01.012 -
Viruses Mar 2018Diagnostic electron microscopy (DEM) was an essential component of viral diagnosis until the development of highly sensitive nucleic acid amplification techniques (NAT).... (Review)
Review
Diagnostic electron microscopy (DEM) was an essential component of viral diagnosis until the development of highly sensitive nucleic acid amplification techniques (NAT). The simple negative staining technique of DEM was applied widely to smallpox diagnosis until the world-wide eradication of the human-specific pathogen in 1980. Since then, the threat of smallpox re-emerging through laboratory escape, molecular manipulation, synthetic biology or bioterrorism has not totally disappeared and would be a major problem in an unvaccinated population. Other animal poxviruses may also emerge as human pathogens. With its rapid results (only a few minutes after arrival of the specimen), no requirement for specific reagents and its "open view", DEM remains an important component of virus diagnosis, particularly because it can easily and reliably distinguish smallpox virus or any other member of the orthopoxvirus (OPV) genus from parapoxviruses (PPV) and the far more common and less serious herpesviruses (herpes simplex and varicella zoster). Preparation, enrichment, examination, internal standards and suitable organisations are discussed to make clear its continuing value as a diagnostic technique.
Topics: Animals; Exanthema; Herpesviridae; Herpesviridae Infections; Humans; Microscopy, Electron; Orthopoxvirus; Poxviridae Infections; Smallpox
PubMed: 29565285
DOI: 10.3390/v10040142 -
Inquiry : a Journal of Medical Care... 2023Monkeypox (MPX) is a zoonotic disease caused by the MPX virus from the poxviridae family of orthopoxviruses. Typically, endemic in central and west Africa, it has now... (Review)
Review
Monkeypox (MPX) is a zoonotic disease caused by the MPX virus from the poxviridae family of orthopoxviruses. Typically, endemic in central and west Africa, it has now become a matter of concern since cases have been reported in non-endemic countries around mid-June 2022, especially in the European region, with the transmission not related to travel. The diagnosis is made by PCR testing of the skin lesions. Even though treatment is symptomatic, antiretrovirals, such as tecovirimat, are used in severe cases. Vaccination with second and third generation vaccines is approved for prophylaxis in high risk individuals. Unfortunately, these options of treatment and prevention are only available in high income countries at the moment. This review, through a thorough literature search of articles from 2017 onward, focuses on epidemiology, clinical manifestations, challenges, treatment, prevention and control of MPX virus and how they can be corelated with other viral outbreaks including COVID-19, Acute Hepatitis of unknown origin, Measles and Dengue, to better predict and therefore prevent its transmission. The previous COVID-19 pandemic increased the disease burden on healthcare infrastructure of low-middle income countries, therefore, this recent MPX outbreak calls for a joint effort from healthcare authorities, political figures, and NGOs to combat the disease and prevent its further spread not only in high income but also in middle- and low-income countries.
Topics: Humans; Monkeypox virus; Pandemics; COVID-19; Disease Outbreaks; Africa, Western
PubMed: 37190997
DOI: 10.1177/00469580231175437 -
Expert Review of Vaccines Jul 2011We still face a threat of orthopoxviruses in the form of biological weapons and emerging zoonoses. Therefore, there is a need to maintain a comprehensive defense... (Review)
Review
We still face a threat of orthopoxviruses in the form of biological weapons and emerging zoonoses. Therefore, there is a need to maintain a comprehensive defense strategy to counter the low-probability, high-impact threat of smallpox, as well as the ongoing threat of naturally occurring orthopoxvirus disease. The currently licensed live-virus smallpox vaccine ACAM2000 is effective, but associated with serious and even life-threatening adverse events. The health threat posed by this vaccine, and other previously licensed vaccines, has prevented many first responders, and even many in the military, from receiving a vaccine against smallpox. At the same time, global immunity produced during the smallpox eradication campaign is waning. Here, we review novel subunit/component vaccines and how they might play roles in unconventional strategies to defend against emerging orthopoxvirus diseases throughout the world and against smallpox used as a weapon of mass destruction.
Topics: Disease Eradication; Humans; Smallpox; Smallpox Vaccine; Vaccination; Variola virus
PubMed: 21806397
DOI: 10.1586/erv.11.46 -
Viruses Oct 2021Orthpoxvirus infection can spread more easily in a population with a waning immunity with the subsequent emergence/re-emergence of the viruses pertaining to this genus....
Orthpoxvirus infection can spread more easily in a population with a waning immunity with the subsequent emergence/re-emergence of the viruses pertaining to this genus. In the last two decades, several cases of Orthopoxvirus, and in particular Cowpoxvirus infections in humans were reported in different parts of the world, possibly due to the suspension of smallpox vaccinations. To date, in Italy, few investigations were conducted on the presence of these infections, and because of this a serosurvey was carried out to evaluate Cowpoxvirus infection in feline colonies situated in the province of Rome, since these are also susceptible to other zoonotic viruses belonging to Orthopoxvirus, and from which humans may contract the infection. The sample design was set at an expected minimum seroprevalence of 7.5%, a 5% standard error and 95% confidence level. In parallel, a serological investigation was conducted using convenience sampling in domestic, exotic and wild susceptible animals of the Latium and Tuscany Regions, which are areas in the jurisdiction of the Istituto Zooprofilattico Sperimentale del Lazio e della Toscana, coordinating this study. The serological methods employed were indirect immunofluorescence for 36 sera of nonhuman primate and virus neutralization for 1198 sera of different species. All the 1234 sera examined were negative for the presence of antibodies against Cowpoxvirus, indicating its limited circulation in the areas of investigation. The methodology applied for the serosurveillance could be adopted in the case of outbreaks of this infection and for the evaluation of the spread of this infection in the area of interest, to obtain essential information crucial for animal and public health policies according to the One Health concept.
Topics: Animals; Animals, Exotic; Animals, Wild; Antibodies, Viral; Cats; Communicable Diseases; Disease Outbreaks; Italy; Orthopoxvirus; Poxviridae Infections; Seroepidemiologic Studies
PubMed: 34696535
DOI: 10.3390/v13102105 -
The Journal of Allergy and Clinical... Dec 2006The global eradication of smallpox was a tremendous achievement made possible by the development of an effective vaccine. Routine vaccination of the general population... (Review)
Review
The global eradication of smallpox was a tremendous achievement made possible by the development of an effective vaccine. Routine vaccination of the general population is no longer recommended. However, stocks of variola virus, the causative agent of smallpox, still exist in 2 secure laboratories, and permanent disposal has been controversial. In addition, there is speculation that variola virus may exist outside of these 2 facilities, and there is a concern that the threat of smallpox will be used as a bioterrorist weapon. In 2002, this concern led to a vaccination campaign in US military and civilian healthcare workers and first responders. Although the historical live virus vaccine has proven efficacy, it also is associated with serious adverse events and rare fatal reactions, particularly in the setting of immunodeficiency and atopic eczema. In addition, this vaccine was historically produced using animal intermediaries in a process that was prone to contamination and not acceptable for current manufacturing standards. Development of alternative poxvirus vaccines is focused on replication-defective viruses, gene-based vectors, and subunit approaches to improve safety and immunogenicity. The conundrum is that in the absence of an intentional release of variola, efficacy evaluation of new candidate vaccines will be limited to animal model testing, which creates new challenges for the vaccine licensure process. Although motivated by the threat of bioterrorism, the hope is for new poxvirus vaccines to have their greatest utility against other pathogenic orthopoxviruses such as monkeypox and for the development of recombinant poxvirus-based vectors to treat and prevent other diseases.
Topics: Animals; Bioterrorism; Clinical Trials as Topic; Dermatitis, Atopic; Humans; Immunologic Deficiency Syndromes; Monkey Diseases; Orthopoxvirus; Poxviridae; Poxviridae Infections; Smallpox; Smallpox Vaccine; Vaccination; Vaccines, Attenuated; Vaccines, Synthetic; Viral Vaccines; Virus Replication
PubMed: 17157663
DOI: 10.1016/j.jaci.2006.09.037 -
Current Drug Targets. Infectious... Mar 2005The potential use of smallpox virus as a bioterror agent and the endemic presence of monkeypox virus in Africa underscores the need for better therapies for... (Review)
Review
The potential use of smallpox virus as a bioterror agent and the endemic presence of monkeypox virus in Africa underscores the need for better therapies for orthopoxvirus infections. The only existing clinical experience treating vaccinia and smallpox infections has been with Marboran, which suggested that antiviral therapies could be effective in treating and preventing smallpox infections, but this compound has not been pursued. Drugs that have been approved for other indications, like cidofovir, could be approved for the treatment of orthopoxvirus infections in a timely manner, and this compound has already been approved for emergency treatment of smallpox and complications from vaccination. Its lack of activity when given orally, however, limits its use in a major outbreak involving large numbers of people exposed to the virus. The discovery and development of new therapies can be achieved more rapidly by drawing on the experience and successes with other antiviral agents, particularly with the herpesviruses. This review will discuss the orthopoxvirus replication cycle in detail noting specific viral functions and their associated gene products that have the potential to serve as new targets for drug design and development. This discussion is designed to help investigators relate these targets to parallel functions and existing assays in other virus systems that have been used successfully in drug development. The rapid progress that has been achieved in recent years should yield new drugs for the treatment of these infections and might also reveal new strategies for antiviral therapy with other viruses.
Topics: Animals; Antiviral Agents; Drug Delivery Systems; Humans; Orthopoxvirus; Transcription, Genetic
PubMed: 15777195
DOI: 10.2174/1568005053174627 -
Travel Medicine and Infectious Disease 2023Monkeypox (Mpox) is a transmissible infection induced by the Monkeypox virus (a double-stranded DNA virus), recognised under the family orthopoxvirus genus. Monkeypox,... (Review)
Review
Monkeypox (Mpox) is a transmissible infection induced by the Monkeypox virus (a double-stranded DNA virus), recognised under the family orthopoxvirus genus. Monkeypox, like endemic diseases, is a substantial concern worldwide; thus, comprehending the pathogenesis and mutagenesis of amino acids is indispensable to combat the infection. According to the World Health Organization's report, about 89 thousand cases with 160 mortalities have been reported from 114 countries worldwide. The conventional orthopoxvirus vaccines developed on live attenuated viruses exempted any clinical validation from combating monkeypox due to inadequate immunogenicity, toxicity, instability, and multiple doses. Therefore, novel drug delivery systems come into the conception with high biological and mechanical characteristics to address the resurgence of Global Monkeypox. The edges of metallic biomaterials, novel molecules, and vaccine development in targeted therapy increase the modulation of the immune response and blockage of host-virus interaction, with enhanced stability for the antigens. Thus, this review strives to comprehend the viral cell pathogenesis concerning amino acid mutagenesis and current epidemiological standards of the Monkeypox disease across the globe. Furthermore, the review also recapitulates the various clinical challenges, current therapies, and progressive nanomedicine utilisation in the Monkeypox outbreak reinforced by various clinical trial reports. The contemporary challenges of novel drug delivery systems in Monkeypox treatment cannot be overlooked, and thus, authors have outlined the future strategies to develop successful nanomedicine to combat monkeypox. Future pandemics are inevitable but can be satisfactorily handled if we comprehend the crises, innovate, and develop cutting-edge technologies, especially by delving into frontiers like nanotechnology.
Topics: Humans; Mpox (monkeypox); Disease Outbreaks; Drug Delivery Systems; Endemic Diseases; Monkeypox virus; Orthopoxvirus
PubMed: 37633474
DOI: 10.1016/j.tmaid.2023.102636 -
Frontiers in Cellular and Infection... 2023is one of the most notorious genus amongst the family. Monkeypox (MP) is a zoonotic disease that has been spreading throughout Africa. The spread is global, and... (Review)
Review
is one of the most notorious genus amongst the family. Monkeypox (MP) is a zoonotic disease that has been spreading throughout Africa. The spread is global, and incidence rates are increasing daily. The spread of the virus is rapid due to human-to-human and animals-to-human transmission. World Health Organization (WHO) has declared monkeypox virus (MPV) as a global health emergency. Since treatment options are limited, it is essential to know the modes of transmission and symptoms to stop disease spread. The information from host-virus interactions revealed significantly expressed genes that are important for the progression of the MP infection. In this review, we highlighted the MP virus structure, transmission modes, and available therapeutic options. Furthermore, this review provides insights for the scientific community to extend their research work in this field.
Topics: Animals; Humans; Monkeypox virus; Mpox (monkeypox); Zoonoses; Africa; Host Microbial Interactions
PubMed: 36844409
DOI: 10.3389/fcimb.2023.1076251