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Discontinuation of vaccination after the completion of Smallpox global eradication program led to a sharp decrease in the level of collective immunity not only to smallpox but also to other orthopoxvirus infections. Over the past 10–15 years, the world has seen an increase in the frequency of diseases caused by smallpox viruses of cows, buffaloes, camels. The outbreak of mpox (a disease caused by the monkey pox virus) occurred in 2022–2023. Analysis of the literature data on the organization of the orthopoxvirus genome suggest that smallpox could have occurred in the past as a result of evolutionary changes in the zoonotic progenitor virus. In this regard, there is a threat of a new particularly dangerous anthropozoonosis, the pathogen of which can occur both naturally and artificially. The aim of the review is to analyze open science published data on aerobiological research with OPVs conducted by the U.S. Department of Defense from 1994-2013, which was a period of restricted research and storage of smallpox virus samples. The authors did not find any publications of the results of aerobiological research with orthopoxviruses conducted by the US Department of Defense after 2013 in open scientific sources. The review presents a data analysis in Russian and English-speaking scientist publication as well as those posted on the Internet. The presented results of aerobiological studies with orthopoxviruses indicate the interest of the US military department in carrying out experimental work of dual use, including monitoring of the properties of orthopoxviruses and a possible change in their pathogenicity for humans, selection of optimal laboratory models for studying the properties of orthopoxviruses, and the possibility of modeling the properties of the smallpox virus when using other orthopoxviruses (cowpox virus, rabbit pox virus, monkey pox virus), modeling of the main characteristics of the disease caused by the smallpox virus in humans and evaluation of the effectiveness of existing and newly developed vaccines against smallpox, comparative study of effectiveness of antiviral drugs for regular or post-exposure prophylaxis of naturally occurring smallpox and monkey smallpox.

Practical colorimetric biosensors were developed for the detections of A29 and A27L proteins which were defined as Monkeypox virus (MPXV) and smallpox target proteins. For this purpose, gold nanoparticles (AuNPs) were synthesized and used to detect specific interaction between heparan sulphate (HS) receptor and A29 or A27L target proteins. This study is the first colorimetric biosensor that was based on the interaction of HS and A29 or A27L protein. In this work first, HS was labeled with AuNPs. When AuNPs labeled HS was incubated with A29 or A27L protein structure, these proteins specifically bounded to HS. Next, obtained AuNP/HS‐A29 or AuNP/HS‐A27L structures began to aggregate, and then difference in absorbance value of AuNP at 530 nm occurred. Absorbance differences at 530 nm were monitored spectroscopically. After experimental parameters were optimized, analytical characteristics of developed biosensors were investigated. As a result, the limit of detection was calculated as 7.93 ng.mL−1 and 6.09 ng.mL−1for A29 protein and A27L, respectively. The relative standard deviation were calculated as 1.97 % and 5.72 % for 25 ng.mL−1 A29 and 12.5 ng.mL−1 A27, respectively. Sample application studies were also performed with the standard addition of A29 and A27L proteins to real serum samples taken from healthy individuals. As a result, very promising results were obtained. [ABSTRACT FROM AUTHOR]

After the abolition of the mandatory smallpox vaccination, the humanity lost the immunity not only to smallpox, but also to infections caused by pathogens of this family (Orthopoxvirus): monkeypox, cowpox, buffalo pox, camelpox. Since the camelpox and African gerbil viruses are the closest to the variola virus (genomic homology is 97%) in phylogenetic and genetic terms, it cannot be ruled out that a mutation in a small fragment of the genome of one of these viruses will lead to the replacement of a relatively safe virus with an epidemically dangerous pathogen. The purpose of is article is to summarize materials on the study of camelpox virus. The sources for this research is scientific articles and other English-language literature available via the Internet. The research method is an analysis of scientific sources on camelpox from the general to the specific. The authors considered the epizootic danger of the virus, its virulence for humans, phylogenetic relationship with other orthopoxviruses, means of specific prevention and treatment of camel pox in camels. The discussion and the results. The causative agent of camelpox causes a nodular-pastular rash on the skin and mucous membranes in Camelus dromedaries and Camelus bactrianus. The disease is contagious, and its epizootics lead to significant economic damage. From December 2008 to May 2009, several laboratory-confirmed cases of camelpox in humans were reported in India, Somalia and eastern Sudan. Nowadays for the identification of the camelpox virus, a RT-PCR test system with primers for the C18L gene is usually offered, which detects only this virus. The established host range of the virus is limited to one animal - the camel. To treat sick camels, chemotherapy drugs are used: cidofovir and tocoverimate (ST-246). For immunoprophylaxis, live and inactivated vaccines are used. The conclusion. Camelpox virus poses a risk to humans in regions where people raise camels and are in close contact with them. The immunodeficient populations of people may serve as an additional «window» for the penetration of this virus into human society. The genetic variability of the virus and the plasticity of its genome make it possible to obtain virus strains with altered properties. Synthetic biology methods create a risk, through small substitutions in the genome of the virus, of turning it into an epidemic danger for humans. Constant monitoring of this disease is necessary, since there is a danger of the transmission of camelpox from Kazakhstan to areas bordering the Russian Federation.

Relevance. The epidemiological situation in the world is characterized by an increase in the incidence of orthopoxvirus infections in humans and animals. In this regard, it is necessary to develop new safe vaccines against these infections.Aim. Conducting preclinical studies on the specific activity of the live vaccine against smallpox and other orthopoxvirus infections VACΔ6 based on the vaccinia virus (VACV) with six deleted virulence genes are presented.Matherials and methods. The studies were performed in accordance with the requirements of the Guidelines for conducting preclinical studies of drugs (immunobiological preparations), the State Pharmacopoeia XIII and the European Pharmacopoeia 7.0.Results and discussion. The vaccine strain VACΔ6 VACV showed significantly reduced neurovirulence in the model of intracerebral administration to suckling mice, and reduced inflammatorynecrotic activity in the model of intradermal administration to rabbits compared to the classical first­generation smallpox live vaccine approved for use in Russia. Preclinical studies of three series of the finished dosage form of the VAC∆6 vaccine showed its authenticity, thermal stability, non­pyrogenicity and safety. Double intradermal vaccination of rabbits at a dose of 106 PFU/animal, a 100% protective effect was provided against the intranasal infection of rabbits with VACV strain HB­-92 at a dose of 1995 LD50 and a double intradermal vaccination of mice at a dose of 106 PFU/animal, full protection was provided against the intranasal infection of mice with ectromelia virus strain K1 at a dose of 56 LD50.Conclusion. Based on the conducted complex of studies, it can be concluded that the created vaccine of the fourth generation VACΔ6 is safer compared to the live smallpox vaccine of the first generation and is not inferior to it in immunogenic and protective properties.

Background: In the last couple of years, viral infections have been leading the globe, considered one of the most widespread and extremely damaging health problems and one of the leading causes of mortality in the modern period. Although several viral infections are discovered, such as SARS CoV-2, Langya Henipavirus, there have only been a limited number of discoveries of possible antiviral drug, and vaccine that have even received authorization for the protection of human health. Recently, another virial infection is infecting worldwide (Monkeypox, and Smallpox), which concerns pharmacists, biochemists, doctors, and healthcare providers about another epidemic. Also, currently no specific treatment is available against Monkeypox. This research gap encouraged us to develop a new molecule to fight against monkeypox and smallpox disease. So, firstly, fifty different curcumin derivatives were collected from natural sources, which are available in the PubChem database, to determine antiviral capabilities against Monkeypox and Smallpox. Material and method: Preliminarily, the molecular docking experiment of fifty different curcumin derivatives were conducted, and the majority of the substances produced the expected binding affinities. Then, twelve curcumin derivatives were picked up for further analysis based on the maximumdocking score. After that, the density functional theory (DFT) was used to determine chemical characterizations such as the highest occupied molecular orbital (HOMO), lowest unoccupied molecular orbital (LUMO), softness, and hardness, etc. Results: The mentioned derivatives demonstrated docking scores greater than -6.80 kcal/mol, and the most significant binding affinity was at -8.90 kcal/mol, even though 12 molecules had higher binding scores (-8.00 kcal/mol to -8.9 kcal/mol), and better than the standard medications. The molecular dynamic simulation is described by root mean square deviation (RMSD) and root-mean-square fluctuation (RMSF), demonstrating that all the compounds might be stable in the physiological system. Conclusion: In conclusion, each derivative of curcumin has outstanding absorption, distribution, metabolism, excretion, and toxicity (ADMET) characteristics. Hence, we recommended the aforementioned curcumin derivatives as potential antiviral agents for the treatment of Monkeypox and Smallpox virus, and more in vivo investigations are warranted to substantiate our findings. [ABSTRACT FROM AUTHOR]

Monkeypox is a zoonotic disease caused by the monkeypox virus, which is a member of the Poxviridae family of viruses. It is transmitted through direct or indirect contact with fluid secretions. Initial symptoms include fever, chills, headache, and malaise, followed by a maculopapular rash that starts on the face and progresses centrifugally. Polymerase chain reaction is the preferred laboratory test for the diagnosis, and management is mostly supportive. The clinical presentation of monkeypox is quite similar to that of another member of the Poxviridae family: smallpox, which wreaked havoc in the 20th century, before being eradicated with the help of the vaccinia virus vaccine in 1977. This vaccine protects not only against smallpox but also monkeypox; therefore, when use of this vaccine was discontinued, monkeypox had a new susceptible population to infect and way to proliferate and evolve. Initially the disease spread in Africa, but now the more evolved monkeypox is quickly spreading to other countries. On July 23, 2022, the World Health Organization declared this multicountry outbreak a public health emergency of international concern. Given its mutating ability and high transmissibility, we need to quickly devise measures to control this virus before it turns into a pandemic. [ABSTRACT FROM AUTHOR]

In May 2022, there was a disturbing news of Monkeypox infection in the United Kingdom and soon after, other incidences of the infection were recorded in the United States and several countries where the disease is not known to be endemic. In this work, we investigate the impact of imperfect vaccination derived primarily from the Smallpox vaccine on the spread of the virus. Our findings suggest that while imperfect vaccines may not provide complete protection against the disease, they can still reduce the transmission of Monkeypox, potentially slowing the spread of the virus in a population.

The monkeypox virus (MPXV) is the cause of a zoonotic infection similar to smallpox. Although it is endemic to Africa, it has recently begun to circulate in other parts of the world. In July 2022, the World Health Organization declared monkeypox an international public health emergency. This review aims to provide an overview of this neglected zoonotic pathogen. MPXV circulates as two distinct clades, the Central African and West African, with case fatality rates of 10.6% and 3.6%, respectively. The risk of infection is greater for those who work with animals or infected individuals. The virus’ entry into the human body provokes both natural and acquired immunity. Although natural killer cells, CD4 + T cells, and CD8 + T cells play an essential role in eradicating MPXV, there is still a gap in the understanding of the host immune response to the virus. Currently, there are no specific therapeutic guidelines for treating monkeypox; however, some antiviral drugs such as tecovirimat and cidofovir may help to abate the severity of the disease. The use of nonpharmaceutical interventions and immunization can reduce the risk of infection. Increased surveillance and identification of monkeypox cases are crucial to understand the constantly shifting epidemiology of this resurging and intimidating disease. The present review provides a detailed perspective on the emergence and circulation of MPXV in human populations, infection risks, human immune response, disease diagnosis and prevention strategies, and future implications, and highlights the importance of the research community engaging more with this disease for an effective global response.

BackgroundIn the last couple of years, viral infections have been leading the globe, considered one of the most widespread and extremely damaging health problems and one of the leading causes of mortality in the modern period. Although several viral infections are discovered, such as SARS CoV-2, Langya Henipavirus, there have only been a limited number of discoveries of possible antiviral drug, and vaccine that have even received authorization for the protection of human health. Recently, another virial infection is infecting worldwide (Monkeypox, and Smallpox), which concerns pharmacists, biochemists, doctors, and healthcare providers about another epidemic. Also, currently no specific treatment is available against Monkeypox. This research gap encouraged us to develop a new molecule to fight against monkeypox and smallpox disease. So, firstly, fifty different curcumin derivatives were collected from natural sources, which are available in the PubChem database, to determine antiviral capabilities against Monkeypox and Smallpox.Material and methodPreliminarily, the molecular docking experiment of fifty different curcumin derivatives were conducted, and the majority of the substances produced the expected binding affinities. Then, twelve curcumin derivatives were picked up for further analysis based on the maximum docking score. After that, the density functional theory (DFT) was used to determine chemical characterizations such as the highest occupied molecular orbital (HOMO), lowest unoccupied molecular orbital (LUMO), softness, and hardness, etc.ResultsThe mentioned derivatives demonstrated docking scores greater than 6.80 kcal/mol, and the most significant binding affinity was at -8.90 kcal/mol, even though 12 molecules had higher binding scores (-8.00 kcal/mol to -8.9 kcal/mol), and better than the standard medications. The molecular dynamic simulation is described by root mean square deviation (RMSD) and root-mean-square fluctuation (RMSF), demonstrating that all the compounds might be stable in the physiological system.ConclusionIn conclusion, each derivative of curcumin has outstanding absorption, distribution, metabolism, excretion, and toxicity (ADMET) characteristics. Hence, we recommended the aforementioned curcumin derivatives as potential antiviral agents for the treatment of Monkeypox and Smallpox virus, and more in vivo investigations are warranted to substantiate our findings.

The monkeypox virus (MPXV) is the cause of a zoonotic infection similar to smallpox. Although it is endemic to Africa, it has recently begun to circulate in other parts of the world. In July 2022, the World Health Organization declared monkeypox an international public health emergency. This review aims to provide an overview of this neglected zoonotic pathogen. MPXV circulates as two distinct clades, the Central African and West African, with case fatality rates of 10.6% and 3.6%, respectively. The risk of infection is greater for those who work with animals or infected individuals. The virus' entry into the human body provokes both natural and acquired immunity. Although natural killer cells, CD4 + T cells, and CD8 + T cells play an essential role in eradicating MPXV, there is still a gap in the understanding of the host immune response to the virus. Currently, there are no specific therapeutic guidelines for treating monkeypox; however, some antiviral drugs such as tecovirimat and cidofovir may help to abate the severity of the disease. The use of nonpharmaceutical interventions and immunization can reduce the risk of infection. Increased surveillance and identification of monkeypox cases are crucial to understand the constantly shifting epidemiology of this resurging and intimidating disease. The present review provides a detailed perspective on the emergence and circulation of MPXV in human populations, infection risks, human immune response, disease diagnosis and prevention strategies, and future implications, and highlights the importance of the research community engaging more with this disease for an effective global response. [ABSTRACT FROM AUTHOR]

This paper is a microbiological voyage throughout the main discoveries and research activities of scholars who studied or taught in this field at Padova University during its 800-year history. The ancient practice of variolization, the so-called miracle of Legnaro and the pellagra debate, whose observations and investigations were driven at Padova even before microbiology was established as a scientific discipline, along with the modern era research activities in the field of agricultural, environmental and food microbiology, undoubtedly suggest the hallmark and everyday role played by microbes in overwhelmingly global, but profoundly human, adventures. [ABSTRACT FROM AUTHOR]

Background: the SARS-CoV 2 pandemic showed us that we were not prepared, that it will not happen again. Objective: to know the level of knowledge about the etiology, symptoms, treatment and prevention of monkeypox disease in health professionals. The study: observational-descriptive, included 251 health professionals, both sexes, voluntary participation. A questionnaire was developed including the variables age, sex and questions about the monkeypox disease, descriptive analysis of the data. Finding: low knowledge about the etiology, symptoms, treatment and prevention of the disease. Less knowledge about forms of contagion (21.9%), incubation time (21.9%), characteristics of the virus (24.3%) and laboratory diagnosis (25.1%); greater knowledge about contagiousness in the incubation period (61.0%), presence of rashes as a characteristic of the disease (53.8%) and lack of specific treatment (52.2%). Conclusion: low knowledge; The formulation of strategies is urgently needed to be able to face possible cases, if necessary. [ABSTRACT FROM AUTHOR]

Background: Pathogens are often assumed to evolve towards reduced virulence, but counterexamples abound. Faced with a new pathogen, such as SARS-CoV-2, it is crucial to be able to forecast the case fatality rate (CFR) and the overall disease burden. Considerable effort has been invested towards developing a mathematical framework for predicting virulence evolution. Although many approaches accurately recapitulate complex outcomes, most rely on an assumed trade-off between CFR and infection rate. It is often impractical to empirically validate this constraint for human pathogens. Methods: A compartment model with parameters tuning the degree to which symptomatic individuals are isolated and the duration of immunity is constructed and evaluated at both short timescales and at equilibrium. Results: We reveal kinetic constraints whereby variation of multiple parameters in concert leads to decreased CFR and increased pathogen fitness, whereas independent variation of the parameters decreases pathogen fitness. Smallpox, SARS-CoV-2, and influenza are analyzed as diverse representatives of human respiratory viruses. We show that highly virulent viruses, such as smallpox, are often constrained by the host behavior, whereas moderately virulent viruses, such as SARS-CoV-2, appear to be typically constrained by the relationship between the duration of immunity and CFR. Conclusions: Evolution of human respiratory epidemics appears to be often kinetically constrained and a reduction in CFR should not be assumed. These results agree with previous work demonstrating an increase in virulence for smallpox and further predict that SARS-CoV-2 is likely to continue presenting a substantial disease burden. Herd immunity against SARS-CoV-2 and viruses with similar life history traits might be unachievable without vaccination. However, partial isolation of symptomatic individuals can have a major effect on the epidemic dynamics not only by reducing the number of fatalities in the short term but also by changing the evolutionary trajectory of moderate CFR viruses towards reduced CFR.

Background: It is often assumed that pathogens evolve towards reduced virulence, but counterexamples abound. Faced with a new pathogen, such as SARS-CoV-2, it is highly desirable to be able to forecast the case fatality rate (CFR) and overall disease burden into the future. Considerable effort has been invested towards the development of a mathematical framework for predicting virulence evolution. Although many approaches accurately recapitulate complex outcomes, most rely on an assumed trade-off between CFR and infection rate. It is often impractical to empirically validate this constraint for human pathogens. Methods: A compartment model with parameters tuning the degree to which symptomatic individuals are isolated and the duration of immunity is constructed and evaluated at both short timescales and at equilibrium (when it exists). Results: We reveal kinetic constraints where the variation of multiple parameters in concert leads to decreased CFR and increased pathogen fitness, whereas independent variation of the parameters decreases pathogen fitness. Smallpox, SARS-CoV-2, and influenza are analyzed as diverse representatives of human respiratory viruses. We show that highly virulent viruses, such as smallpox, are likely often constrained by host behavior, whereas moderately virulent viruses, such as SARS-CoV-2, appear to be typically constrained by the relationship between the duration of immunity and CFR. Conclusions: Evolution of human respiratory epidemics appears to be often kinetically constrained and a reduction in CFR should not be assumed. Our findings imply that, without continued public health intervention, SARS-CoV-2 is likely to continue presenting a substantial disease burden. The existence of a parameter regime admitting endemic equilibrium suggests that herd immunity is unachievable. However, we demonstrate that even partial isolation of symptomatic individuals can have a major effect not only by reducing the number of fatalities in the short term but also by potentially changing the evolutionary trajectory of the virus towards reduced CFR.

The review contains a brief analysis of the results of investigations conducted during 40 years after smallpox eradication and directed to study genomic organization and evolution of variola virus (VARV) and development of modern diagnostics, vaccines and chemotherapies of smallpox and other zoonotic orthopoxviral infections of humans. Taking into account that smallpox vaccination in several cases had adverse side effects, WHO recommended ceasing this vaccination after 1980 in all countries of the world. The result of this decision is that the mankind lost the collective immunity not only to smallpox, but also to other zoonotic orthopoxvirus infections. The ever more frequently recorded human cases of zoonotic orthopoxvirus infections force to renew consideration of the problem of possible smallpox reemergence resulting from natural evolution of these viruses. Analysis of the available archive data on smallpox epidemics, the history of ancient civilizations, and the newest data on the evolutionary relationship of orthopoxviruses has allowed us to hypothesize that VARV could have repeatedly reemerged via evolutionary changes in a zoonotic ancestor virus and then disappeared because of insufficient population size of isolated ancient civilizations. Only the historically last smallpox pandemic continued for a long time and was contained and stopped in the 20th century thanks to the joint efforts of medics and scientists from many countries under the aegis of WHO. Thus, there is no fundamental prohibition on potential reemergence of smallpox or a similar human disease in future in the course of natural evolution of the currently existing zoonotic orthopoxviruses. Correspondingly, it is of the utmost importance to develop and widely adopt state-of-the-art methods for efficient and rapid species-specific diagnosis of all orthopoxvirus species pathogenic for humans, VARV included. It is also most important to develop new safe methods for prevention and therapy of human orthopoxvirus infections.

This paper is a microbiological voyage throughout the main discoveries and research activities of scholars who studied or taught in this field at Padova University during its 800-year history. The ancient practice of variolization, the so-called miracle of Legnaro and the pellagra debate, whose observations and investigations were driven at Padova even before microbiology was established as a scientific discipline, along with the modern era research activities in the field of agricultural, environmental and food microbiology, undoubtedly suggest the hallmark and everyday role played by microbes in overwhelmingly global, but profoundly human, adventures.

Objective. Determination of the effectiveness of final disinfection treatment of virological laboratory rooms (with the passageway room between two entries) in the isolated zone used for work with pathogenic agents, of the maximum containment laboratory by fumigation with formaldehyde vapors, including the assessment of the optimal amount of formalin. Experimental evaluation of the suitability of the aerosol generator “Ultrasprayer P-60” for the final disinfection of the premises of the “contagious” zone with the “dry steam” of hydrogen peroxide. Materials and methods. The effectiveness of the final disinfection of the surfaces in the premises of the “infectious” zone of the maximum containment laboratory was evaluated using cambric test objects contaminated by the spore-forming test-culture B. thuringiensis. Results and discussion. As a result of experimental studies, the required amount of formalin was determined that is sufficient to completely inactivate possible infectious contaminants that may be potentially located on the surfaces of equipment and rooms located in the “contagious” zone of the maximum containment laboratory, during fumigation with formaldehyde vapors. The amount of formalin specified experimentally turned out to be 1.4 times more than the recommended by regulatory documentation for unventilated rooms, but 2-2.5 times less than that used for final disinfection of maximum containment laboratory previously. Disinfection treatment of the premises and equipment located in the “contagious” zone of the laboratory with 6 % hydrogen peroxide “dry steam”, which is the active agent of Disargent drug, sprayed through the «Ultrasprayer р-60» aerosol generator, was more effective than spray irrigation with 6 % hydrogen peroxide aerosol generated using pneumatic aerosol nozzles. At the same time, it was possible to achieve sufficiently complete inactivation of the test microorganism located on test objects at a concentration of 1·106 cells/cm2, by increasing the concentration of hydrogen peroxide sprayed by the device up to 10 %. However, even in that case, viable test microorganisms remained in the hidden cavities of the equipment and office machinery, which makes further studies relevant to establish the optimal concentration of hydrogen peroxide during the final disinfection with an «Ultrasprayer р-60» aerosol generator or similar equipment from other manufacturers.

A new taxon of the subfamily Chordopoxvirinae that may represent a new genus of smallpox viruses is considered in this review. The distribution of gray squirrels (Sciurus carolinensis) throughout the UK during the 20th century and the decrease in the population of red squirrels (Sciurus vulgaris) is one of the most well-documented cases of ecological change of local fauna by the introduced species. The tendency to expand the distribution of the smallpox virus from Great Britain to the Western part of Europe has been noted. The genetic peculiarities of the genome of the poxvirus of squirrels, which determine its biological properties, as well as evolutionary relationships with other poxviruses, are separately described. Determination of the size of the genome by restriction analysis, sequencing of the whole genome, determination of the content of G/C nucleotide pairs, and functional mapping of the majority of genes made it possible to construct a phylogenetic tree. Phylogenetic analysis shows that this is a new representative of the subfamily Chordоpoxvirinae located between the viruses of the molluscum contagiosum and parapoxviruses. Serological and molecular biological methods are used to reveal and identify the causative agent of smallpox. The use of electron microscopy is limited in grey squirrels, due to the absence of organ damage and reproduction of the virus. Identification of the DNA of the causative agent of poxvirus of squirrels based on the use of different types of polymerase chain reaction (nested and in real time) overcomes all these limitations.

The eradication of smallpox is one of the greatest medical successes in history. Vaccinia virus was made famous by being the virus used in the live vaccine that enabled this feat. Nearly 40 years on from that success, this prototypical poxvirus continues to empower the exploration of fundamental biology and the potential to develop therapeutics against some of the major causes of death and disease in the modern world. [ABSTRACT FROM AUTHOR]

The article focuses on the construction of an infectious horsepox virus from synthesized DNA. It mentions that the study ease the development of smallpox virus (variola) using synthetic biology. It focuses on the benefits and risks of synthetic biology. It focuses on the construction of an infectious horsepox virus vaccine from chemically synthesized DNA fragments.

The article focuses on the study of horsepox and the need for new methods, more transparency, and oversight for experiments with pandemic risks. It mentions that horsepox and smallpox are orthopox viruses. It mentions that the researchers have decreased uncertainties and addressed barriers that scientist encounter to synthesize smallpox.

The article presents author's comments on the synthetic horsepox viruses with thedebate on dual use research. It focuses on the dual use research of concern (DURC), as the method that can be used to assemble horsepox virus can be used to develop variola which is the virus that causes smallpox. It focuses on recovering vaccinia virus (VACV) from a bacmid.

The article discusses the history of the smallpox vaccine. Topics include the discovery of the vaccination by scientist Edward Jenner in 1796, the distribution of the Jennerian vaccine worldwide, and the discovery by British researcher Allan Downie which reveals the distinction between the viruses and the vaccinia virus using immunological assays. Information on the use of Next-Generation Sequencing (NGS) technologies in the genomic research of old and modern smallpox vaccines is also given.

Concerns regarding outbreaks of human monkeypox or the potential reintroduction of smallpox into an immunological naïve population have prompted the development of animal models and countermeasures. Here we present a marmoset model of monkeypox and smallpox disease utilizing a relevant poxvirus via a natural exposure route. We found that 1000 plaque forming units (PFU) of Monkeypox virus was sufficient to recapitulate smallpox disease, to include an incubation period of approximately 13 days, followed by the onset of rash, and death between 15 and 17 days. Temporally accurate manifestation of viremia and oral shedding were also features. The number of lesions ranged from no lesions to 299, the most reported in a marmoset exposed to a poxvirus. To both evaluate the efficacy of our antibodies and the applicability of the model system, marmosets were prophylactically treated with two monoclonal antibodies, c7D11 and c8A. Of three marmosets, two were completely free of disease and a single marmoset died 8 days after the mock (n = 1) or PBS control(s) (n = 2). Evaluation of the serum levels of the three animals provided a possible explanation to the animal succumbing to disease. Interestingly, more females had lesions (and a greater number of lesions) and lower viral burden (viremia and oral shedding) than males in our studies, suggesting a possible gender effect. [ABSTRACT FROM AUTHOR]

Background: Modified Vaccinia Ankara (MVA) is a live, viral vaccine under advanced development as a non-replicating smallpox vaccine. A randomised, double-blind, placebo-controlled phase III clinical trial was conducted to demonstrate the humoral immunogenic equivalence of three consecutively manufactured MVA production lots, and to confirm the safety and tolerability of MVA focusing on cardiac readouts. Methods: The trial was conducted at 34 sites in the US. Vaccinia-naïve adults aged 18-40 years were randomly allocated to one of four groups using a 1:1:1:1 randomization scheme. Subjects received either two MVA injections from three consecutive lots (Groups 1-3), or two placebo injections (Group 4), four weeks apart. Everyone except personnel involved in vaccine handling and administration was blinded to treatment. Safety assessment focused on cardiac monitoring throughout the trial. Vaccinia-specific antibody titers were measured using a Plaque Reduction Neutralization Test (PRNT) and an Enzyme-Linked Immunosorbent Assay (ELISA). The primary immunogenicity endpoint was Geometric Mean Titers (GMTs) after two MVA vaccinations measured by PRNT at trial visit 4. This trial is registered with ClinicalTrials.gov, number NCT01144637. Results: Between March 2013 and May 2014, 4005 subjects were enrolled and received at least one injection of MVA (n = 3003) or placebo (n = 1002). The three MVA lots induced equivalent antibody titers two weeks after the second vaccination, with seroconversion rates of 99·8% (PRNT) and 99·7% (ELISA). Overall, 180 (6·0%) subjects receiving MVA and 29 (2·9%) subjects in the placebo group reported at least one unsolicited Adverse Event (AE) that was considered trial-related. Vaccination was well tolerated without significant safety concerns, particularly regarding cardiac assessment. Conclusions: The neutralizing and total antibody titers induced by each of the three lots were equivalent. No significant safety concerns emerged in this healthy trial population, especially regarding cardiac safety, thus confirming the excellent safety and tolerability profile of MVA. Trial registration: ClinicalTrials.gov [ABSTRACT FROM AUTHOR]

Although it has been >30 years since the eradication of smallpox, the unearthing of well-preserved tissue material in which the virus may reside has called into question the viability of variola virus decades or centuries after its original occurrence. Experimental data to address the long-term stability and viability of the virus are limited. There are several instances of well-preserved corpses and tissues that have been examined for poxvirus viability and viral DNA. These historical specimens cause concern for potential exposures, and each situation should be approached cautiously and independently with the available information. Nevertheless, these specimens provide information on the history of a major disease and vaccination against it. Download MP3 Length: 0:52

The article discusses the transcriptional and translational process of the poxviruses pathoggen. It states that poxviruses remains dependent on host ribosomes to translate mRNAs. It mentions that poxviruses evade antiviral response by encoding proteins that target protein kinase RNA-activated (PKR) and limit production of double stranded RNA (dsRNA).

The article discusses how to develop viruses as weapons to prevent cancer. Topics include the approach to oncolysis, the difficulty of assessing the reason for success or failure of clinical trials with oncolytic viruses due to viral replication, and the improvement of oncolysis efficacy by pharmacological down-modulation of preexisting and induced antiviral immune responses.

Background: In May 2022, a case of monkeypox (currently known as "mpox") with no history of overseas travel was reported in the United Kingdom, followed by reports of infections reported in Europe, the United States, and other countries worldwide. Due to the significant overlap in immune responses among viruses of the genus Orthopoxvirus (including smallpox virus, mpox virus, and vaccinia virus), it is believed that cross-immunity can be achieved by administering the smallpox virus vaccine. In Japan, a smallpox vaccine (LC16m8 strain vaccine) has been approved; however, there was no regulatory approval for the mpox vaccine during the design of this study. Although it is believed that individuals exposed to the mpox virus may receive smallpox vaccination as mpox prophylaxis, the existing evidence is not clear., Objective: The primary objective was to evaluate the efficacy of the LC16m8 strain vaccine, approved for smallpox in Japan, for postexposure prophylaxis against mpox when administered to close contacts of individuals with mpox. The secondary objective was to investigate the safety of the vaccine for postexposure prophylaxis against mpox., Methods: The study aimed to enroll 100 vaccinated participants who had been identified as close contacts of individuals with mpox. Consent was obtained, and the participants are inoculated with the vaccine. Daily recordings of symptoms (body temperature, headache, rash, and side effects) were made until day 21 and then again on day 28. Furthermore, additional evaluations of adverse events were performed by the investigators on days 7, 14, 21, and 28. Considering that the maximum incubation period for mpox is 21 days, the primary end point is the presence or absence of the disease 21 days after close contact. The primary analysis focused on cases within 4 days of intense contact as it has been reported that vaccination within this timeframe can reduce the incidence of the disease., Results: The first trial participant was enrolled on July 28, 2022, and the research period concluded in March 2023. The study results will be published in a peer-reviewed scientific journal., Conclusions: This study allowed us to investigate the efficacy and safety of the LC16m8 strain vaccine in postexposure prophylaxis against mpox., Trial Registration: Japan Registry of Clinical Trials jRCTs031220137; https://jrct.niph.go.jp/en-latest-detail/jRCTs031220137., International Registered Report Identifier (irrid): DERR1-10.2196/46955., (©Rina Yano, Junko Terada-Hirashima, Yukari Uemura, Noriko Tomita, Yosuke Shimizu, Haruka Iwasaki, Nobumasa Okumura, Tetsuya Suzuki, Sho Saito, Mugen Ujiie, Wataru Sugiura, Norio Ohmagari. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 25.08.2023.)