Smallpox Research Articles

A-270 Evaluation of a multiplex panel to determine antibody profile to monkeypox virus in vaccinated, exposed, and naïve individuals

Abstract Background Monkeypox Virus (MPXV) is a double-stranded DNA virus of the Orthopoxvirus genus that causes Mpox disease with symptoms such as swollen lymph nodes, chills, exhaustion, and blisters that appear on the face, inside the mouth, hands, feet etc. The genus orthopoxvirus (OPXV) has four species, namely, MPXV, smallpox-causing variola major virus (VARV), variola minor virus, and cowpox virus (CPXV), that cause disease in humans. In 1980, the World Health Assembly declared that smallpox had been eradicated due to a successful global vaccination program. This vaccine also provided cross-protection against other OPXV. Historically, the pox disease was rarely seen outside West and Central Africa. The first case of Mpox was identified in 1970 in a 9-year-old boy from the Democratic Republic of Congo (DRC), two years after the smallpox vaccination was discontinued. Since then, it has been reported in 11 African countries. In 2003, the first Mpox outbreak outside of Africa was in the USA and was linked to contact with infected pet prairie dogs. The recent 2022-2023 Mpox outbreak has generated renewed interest in the scientific community to understand the level of OPXV-specific immunity in the various geographic regions, among different age groups, and especially in the risk groups and its impact on future outbreaks by using integrated serosurveillance. To meet the need of the hour, we developed a novel multiplex assay for the detection of human IgG antibodies using Luminex® xMAP® technology for the detection of the human IgG profiles. Methods We have evaluated 11 different recombinant antigens from VARV, Vaccinia virus (VACV), and MPXV in a multiplex assay for detecting human IgG antibodies to OPXV using Luminex® xMAP® technology. We have covalently coupled magnetic fluorescent microspheres to three recombinant proteins from VARV, three from VACV, and five from MPXV to interrogate IgG responses. This 15-plex assay also includes four internal controls that assure the assay and reagent performance. In this preliminary evaluation, we have tested 84 de-identified serum and plasma from healthy subjects. We evaluated 24 serum samples of MPXV-exposed individuals procured commercially. We performed principal component analysis to determine which of these 11 antigens contributed the maximum differential and a result analysis algorithm was developed to predict these individuals' positive and negative antibody outcomes. Results The healthy subjects that were assumed to have been vaccinated showed positive response to A35R of MPXV; A36R of VARV, A33R of VACV, the homologous proteins in the three species and were distinct from unvaccinated younger individuals. There was some reactivity with B6R of MPXV protein. In MPXV-exposed subjects, we observed strong positive antibody responses to A35R of MPXV, A36R of VARV, A33R of VACV, and B6R of MPXV proteins in 19 out of 24 individuals. Fifteen individuals showed a moderate positive response to the A27L protein of VACV, and 8 out of 24 showed a weak positive response to the A29 protein of MPXV. Conclusions This panel is a useful tool to understand the level of OPXV-specific immunity by measuring IgG profiles for successful serosurveillance programs for public health.

Development of Smallpox Antibody Testing and Surveillance Following Smallpox Vaccination in the Republic of Korea.

Background: Despite its global eradication in 1977, smallpox remains a concern owing to its potential as a biological agent, thereby prompting the ongoing development and utilization of its vaccine. Vaccination with the Vaccinia virus induces immunity against variola virus, the causative agent of smallpox; however, this immunity does not extend to viruses of different genera within the Poxviridae family. In this study, we aimed to assess the efficacy of an enzyme-linked immunosorbent assay (ELISA) method utilizing Vaccinia virus and recombinant A27L antigen for detecting antibodies against smallpox. Methods. An analysis of the serum from 20 individuals pre- and post-vaccination with the CJ strain (CJ50300) revealed neutralizing antibodies, which were confirmed using the plaque reduction neutralization test (PRNT). The ELISA method, validated with a PRNT50 cut-off value of >4, exhibited a sensitivity and specificity of >95% and was particularly reactive with the inactivated virus. Furthermore, adherence to the smallpox vaccination policy revealed significant differences in Orthopoxvirus antibody levels among 300 individuals of different age groups. These findings highlight the reliability and efficacy of the ELISA method in detecting post-vaccination antibodies and contribute significantly to diagnostic methods to prepare for potential smallpox resurgence and bioterrorism threats.

Vaccinations for emerging and re-emerging viral diseases

Emerging or re-emerging viral diseases have apandemic potential and threaten global health. Vaccination is of crucial importance in the prevention of emerging and re-emerging viral diseases. Description of the current status of vaccine development against Filoviridae, highly pathogenic coronaviruses, smallpox viruses, influenza viruses and arboviruses. Focused literature search. The World Health Organization (WHO) regularly publishes alist of infectious diseases that are expected to pose amajor threat to humanity as they are could potentially trigger new pandemics; however, in addition to these human-to-human transmissible diseases, some arboviruses also have pandemic potential. In recent years numerous new vaccines, some of which are highly effective, have been licensed against new and re-emerging viral diseases and other promising vaccine candidates are currently in development. There are still gaps in the development of vaccines in the area of Filoviridae and highly pathogenic coronaviruses. Vaccinations against smallpox viruses have been available for a long time. Developing influenza vaccines against novel strains in atimely manner is achallenge and universal influenza vaccines could be apossible solution. Modern vaccines are available against the arboviruses dengue and Chikungunya fever.

Prevention and Control of Rheumatic Fever in India – A Blue Print for Introduction of a Pragmatic Program with Limited Resources

“Eliminate rheumatic fever (RF) and minimize the burden of rheumatic heart disease by 2025” is the goal of World Heart Federation (WHF). The most important step to achieve the goal of WHF is the implementation of the prevention and control of RF in India. The program can be implemented with minimal fund allocation from government making use of the existing man power in the government and private health sector and schools with the concurrence of National Health Mission, Ministry of Health and Family Welfare, Ministry of Public Education and under the guidance of Cardiological Society of India, National Rheumatic Heart Consortium, Rheumatic Heart Club India, Association of Physicians of India, Indian Academy of Pediatrics, and Association of Otolaryngologists of India. By the successful implementation of this program, the children of 5–15 years in India can be protected from RF. India eradicated small pox in 1980 and Polio 2012. With this program, we can start our efforts to eliminate RF by 2025.

Monkeypox: A Growing Global Health Challenge and the Need for Vigilant Preparedness

The Ongoing Public Health Challenge of Monkeypox Monkeypox is relatively a new threat to the global community as it has brought into focus the issue of improved surveillance and response to infectious diseases[1]. Initially, a rather exotic zoonotic pathogen limited to certain regions of Central and West Africa, monkeypox is being detected in the countries that previously did not report its occurrence, which creates new challenges for the health care systems of the world[2]. Understanding the Disease Monkeypox is an infectious disease that results from the attack of monkeypox virus which is in the Ortho poxvirus group of the virus family Poxviridae though the smallpox virus has been eradicated. The disease has some symptoms are similar to smallpox and includes fever, body aches, and rash that goes through different stages. Despite the fact that monkeypox is less severe when compared with smallpox, significant morbidity and potentially mortality cannot be ruled out[3]. Direct human-to-human transmission is by contact with infected body fluids, aerosols, or fomites such as used clothing, beddings among others. Recent epidemics have been experienced in the urban areas as this makes it easier for the virus to spread due to high population densities. This has transformed the disease from one which affected isolated African communities to a problem in developed, globally connected cities[4]. Why Should We Be Concerned? The stoppage of smallpox vaccination has exposed the people to Ortho poxviruses such as monkeypox. The constant risk of getting zoonotic diseases due to factors such as deforestation, urbanization and close interaction with animals means that diseases, which are mainly associated with animals, can easily infect human beings. Furthermore, the flexibility in the global interconnectivity of today’s world through travel and business has facilitated the spread of the virus across the borders. In 2022, 34 monkeypox cases were reported in European countries, the Americas, and other areas of the world, where the disease had not been identified[5, 6]. The Public Health Response To this recent outbreak of the disease, the WHO and the CDC have scaled up awareness campaigns and encouraged surveillance as well as put in place measures to contain the spread of the disease. Mass vaccination campaigns using smallpox vaccines that work against monkeypox have been intensified in the affected countries, however, there are several problems with implementing this approach: the difficulties of delivering vaccines in time and the scarcity of the vaccines themselves[7]. These are important in educating communities on how to avoid the disease and this include avoiding contact with sick persons, washing hands regularly and consulting a doctor when experiencing early symptoms of the disease. It also means that health systems need to be ready and able to identify such patients and isolate them to avoid spreading of the virus[8, 9]. Looking Forward The spread of monkeypox in the non-endemic countries is a cause of concern and questions the efficiency of our societies’ prevention, detection, and controlling of infectious diseases. Even as the current outbreaks have informed the world of the virus, it is important to note that this is not a one-off case[10]. Zoonotic diseases, which can be transmitted from animals to people, will remain a threat into the future as people increase in numbers and expand their living space into the domain of wildlife. The fight against monkeypox is the fight against all other infectious diseases that can be most effectively fought for with a proper approach and mutual cooperation of all countries[11]. Monkeypox is not as dangerous as some other infectious diseases but looking at the example of how this disease affected people one can conclude that public health cannot be unguarded. Prevention of such diseases in the future would require increased investment in the global health care system, outcome of research on new diseases and vaccination exercises. We cannot afford to wait for another pandemic to happen in order to start acting[12, 13].

Five centuries of consanguinity, isolation, health, and conflict in Las Gobas: A Northern Medieval Iberian necropolis.

Between the 8th and 11th centuries CE, the Iberian Peninsula underwent profound upheaval due to the Umayyad invasion against the Visigoths, resulting in population shifts and lasting demographic impacts. Our understanding of this period is hindered by limited written sources and few archaeogenetic studies. We analyzed 33 individuals from Las Gobas, a necropolis in northern Spain, spanning the 7th to 11th centuries. By combining archaeological and osteological data with kinship, metagenomics, and ancestry analyses, we investigate conflicts, health, and demography of these individuals. We reveal intricate family relationships and genetic continuity within a consanguineous population while also identifying several zoonoses indicative of close interactions with animals. Notably, one individual was infected with a variola virus phylogenetically clustering with the northern European variola complex between ~885 and 1000 CE. Last, we did not detect a significant increase of North African or Middle East ancestries over time since the Islamic conquest of Iberia, possibly because this community remained relatively isolated.

Monkeypox: A Global Challenge - An Overview

Monkeypox is a zoonosis caused by an orthopoxvirus named monkeypox virus MPX, structurally related to smallpox virus, enveloped, brick shaped, replicates in cytoplasm. Currently spreading throughout Africa & different parts of world. Has two distinct clades, West African and Central African (Congo Basin) clades. It manifests as rashes, concentrated on face & extremities like palms & soles. Both humoral and cell mediated immunity are seen in host, diagnosed by polymerase chain reaction PCR and various serological tests. Patients receive supportive treatments along with antiviral drugs. Presently FDA approved new Mpox vaccines. Scientific community needs to extend their research work to enhance knowledge in this field. This review briefs about monkeypox in human life in context of ongoing outbreaks around the world.

Essential and multifunctional mpox virus E5 helicase-primase in double and single hexamer.

An outbreak of mpox virus in May 2022 has spread over 110 nonpandemic regions in the world, posing a great threat to global health. Mpox virus E5, a helicase-primase, plays an essential role in DNA replication, but the molecular mechanisms are elusive. Here, we report seven structures of mpox virus E5 in a double hexamer (DH) and six in single hexamer in different conformations, indicating a rotation mechanism for helicase and a coupling action for primase. The DH is formed through the interface of zinc-binding domains, and the central channel density indicates potential double-stranded DNA (dsDNA), which helps to identify dsDNA binding residues Arg249, Lys286, Lys315, and Lys317. Our work is important not only for understanding poxviral DNA replication but also for the development of novel therapeutics for serious poxviral infections including smallpox virus and mpox virus.

Aptamer and aptasensor technology for diagnosis of infectious diseases: A mini review

BackgroundAptamers are not so new a concept, however, it is scarcely discussed by medical fraternity. Aptamers are potent, new identification molecules set to rope in a new technique in the diagnostic arena. Aptamers have started almost a revolution in diagnostic assays since their discovery in the 90s. (Radu S. Current and previous disease outbreaks around the world, U.S. News & World Report. 2020 Mar 13 [cited 2024 Jun 17]. Available from: https://www.usnews.com/news/best-countries/slideshows/20-pandemic-and-epidemic-diseases-according-to-who) provides an overview of pandemics and epidemics as reported by the WHO. It is interesting to note that several endemic and epidemic diseases viz. Chikungunya, Cholera, Crimean-Congo haemorrhagic fever, Ebola virus disease, Hendra virus infection, Influenza, Lassa fever, Marburg virus disease, Meningitis, MERS-CoV (Middle East Respiratory Syndrome Corona Virus), Monkeypox, Nipah virus infection, Novel coronavirus, Plague, Rift Valley fever, SARS (Severe Acute Respiratory Syndrome), Smallpox, Tularaemia, Yellow fever, and Zika virus disease have been identified by the WHO and are being explored for applicability of aptamer technology in their identification. ObjectivesOne of the most important necessities to control epidemic or pandemic diseases is early diagnosis. However, the majority of the diagnostic tests for these diseases are available only in tertiary care centres. The objective of this review is to discuss the potential of aptamer technology to provide undemanding, simple, specific, sensitive, and cost-effective diagnostic assays that are useable in remote and field conditions. ContentHere, we discuss recent advances and approaches in aptamer and aptamer engineering useful in the diagnosis of infectious and non-infectious conditions. This review also discusses a few sensing discoveries which are a gift of advanced engineering and technology using optical and electrochemical aptasensors. It's still a long way to go, and we need to take into account the technological challenges being faced by aptamer-aptasensor technology.

Navigating the human-monkeypox virus interactome: HuPoxNET atlas reveals functional insights.

Monkeypox virus, a close relative of variola virus, has significantly increased the incidence of monkeypox disease in humans, with several clinical symptoms. The sporadic spread of the disease outbreaks has resulted in the need for a comprehensive understanding of the molecular mechanisms underlying disease infection and potential therapeutic targets. Protein-protein interactions play a crucial role in various cellular processes and regulate different immune signals during virus infection. Computational algorithms have gained high significance in the prediction of potential protein interaction pairs. Here, we developed a comprehensive database called HuPoxNET (https://kaabil.net/hupoxnet/) using the state-of-the-art MERN stack technology. The database leverages two sequence-based computational models to predict strain-specific protein-protein interactions between human and monkeypox virus proteins. Furthermore, various protein annotations of the human and viral proteins such as gene ontology, KEGG pathways, subcellular localization, protein domains, and novel drug targets identified from our study are also available on the database. HuPoxNET is a user-friendly platform for the scientific community to gain more insights into the monkeypox disease infection and aid in the development of therapeutic drugs against the disease.

Mpox and related poxviruses: A literature review of evolution, pathophysiology, and clinical manifestations

The recently re-emerged mpox (monkeypox) virus that causes mpox disease is a member of genus Orthopoxvirus and has unprecedentedly spread worldwide. Numerous studies have contributed to our understanding of its evolution, pathophysiology, and clinical manifestations. The current outbreak of the mpox virus depicts its novel route of transmission as a new variant. However, the exact reason for its transition from an epidemic to a pandemic remains unclear. Furthermore, other poxviruses such as vaccinia virus, variola virus, and cowpox virus, also belong to the same genus, Orthopoxvirus. In the present review, our objective was to summarize the evidence on evolution, pathophysiology, and clinical manifestations of mpox virus and its related poxviruses. The present review would aid in a better understanding of the current circulating mpox virus and its differences from other poxviruses. In addition, the shared genetic factors contributing to virulence in these Orthopoxvirus highlight their evolutionary connections and genetic similarities. While they exhibit differences in virulence, studying these genetic relationships is crucial for understanding their biology, pathogenicity, and the development of effective vaccines and antiviral therapeutics to curb mpox disease.

Update on Monkeypox Virus Infection

The World Health Organization declared the 2022 Monkeypox outbreak as a Public Health Emergency of International Concern, reflecting the rapid spread of infections in non-endemic countries. Since 2022, more than 95,000 confirmed cases with 185 deaths were reported in at least 117 countries, most of them in Europe and USA. Gender-based studies documented preponderance in men (96.8%). Most of them were men who have sex with men (MSM) suggesting the sexual route as the main way of transmission. Mpox infection is usually transmitted by close contact through body fluids, and genital secretions. Exposure to infected respiratory droplets occurs after prolonged exposure. Indirect contact is less frequent. Incubation period is in average 12 days. Prodromal symptoms are systemic and nonspecific succeed with lymphadenopathy. Eruptive rash is changing from macules-papules-blisters-pustules to scabs. Diagnosis is based on clinical occurrence of typical skin and/or mucosal lesions, systemic symptoms, and potential contact to a Mpox-infected individual. The preferred diagnostic test is real-time or conventional polymerase chain reaction (PCR). Laboratory tests based on the detection of antigens or antibodies are not used due to serological cross-reactivity with other orthopoxviruses. The world health authorities agree that smallpox vaccines protect against Mpox infection due to the antigenic similarity between both viruses. New vaccine approved is MVA-BN which contain an attenuated form of vaccinia virus “Ankara” related to the smallpox virus. Antivirals are used to treat Mpox infection, namely cidofovir, tecovirimat and brincidofovir. Individual and universal protective measures should be used to prevent the spread of Mpox viral infection.

Analysis of aerobiological studies with orthopoxviruses by U.S. Department of Defense

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.

Public Policy and Economic Development: The Government of India’s Role for its Development during the Covid-19 Pandemic in India

The world had witnessed several epidemics such as the Spanish Flu of 1918, outbreak of HIV/AIDS, SARS, MERS and Ebola. In the past, India had to deal with diseases such as the small pox, plague and polio. All of these individually had been pretty severe episodes. The Covid-19 which had originated in China in December 2019 and over the next few months rapidly spread to almost all countries of the world can potentially turn out to be the biggest health crisis in our human history. India recorded the first case of the Covid-19 disease on 30th January, 2020. Since then the new confirmed cases have increased steadily and significantly in India. The significant number of causalities also happened in many countries which includes India due to the Covid-19. Many experts have called this a Black Swan event for the global economy. The economic impact of the COVID-19 pandemic in India is largely disruptive. The growth of the economy has slowed down due to shutdown of different many productions channels. But the central government of India has managed through its public policies extremely well in order to overcome this economic slowdown and improved its economic development in a very remarkable speedy way.

Monkeypox infection and pregnancy in lower and middle-income countries: Precautions & recommendations.

Monkeypox (MPX), an orthopoxviral disease endemic in Africa, is now a public health emergency of international concern (PHEIC) as declared by the World Health Organization in July 2023. Although it is generally mild, the overall case fatality rate was reported to be 3%, and the basic reproduction number (R0) is > 1 in men who have sex with men (MSM, i.e., Portugal (1.4), the United Kingdom (1.6), and Spain (1.8)). However, R0 is < 1 in other settings. In concordance with the smallpox virus, it is also expected to increase the risk of adverse outcomes for both the mother and the fetus. The outcomes of the disease in an immunocompromised state of pregnancy are scary, showing high mortality and morbidity of both mother and fetus, with up to a 75% risk of fetal side effects and a 25% risk of severe maternal diseases. Therefore, it warrants timely diagnosis and intervention. The reverse transcription polymerase chain reaction (RT PCR) test is the standard approach to diagnosis. We summarized the recent findings of MPX on pregnancy, and the associated risk factors. We also give recommendations for active fetal surveillance, perinatal care, and good reporting to improve outcomes. The available vaccines have shown promise for primary disease prevention.

Old stories, new cases. Viral infectious diseases and children's health

During the 20th century, smallpox has produced between 300–and 500 million victims. In 1796, Edward Jenner conducted one of the first modern immunizations when he inoculated an 8-year-old boy using material from a cowpox lesion. In 1959, WHO (World Health Organization) launched the Smallpox Eradication Programme. By 1980, WHO declared smallpox officially eradicated. Due to genetic and antigenic similarities between the monkeypox and smallpox viruses, the cessation of smallpox vaccination since 1980′s contributed to the wanning of cross‐protection against monkeypox (mpox). Outbreaks of human mpox has spread across 110 countries.In 1916 and 1952, two major poliovirus outbreaks took place in the USA. The virus killed or paralyzed over half a million people yearly. Introduction of the inactivated polio vaccine (IPV,1955) and oral polio virus (OPV,1963) led to decline in the number of cases by 99.99 %. The Global Polio Eradication Initiative (GPEI) was launched in 1988 and five of six WHO regions have been certified free of wild polio virus (WPV), except Eastern Mediterranean region. Africa had been declared WPV free, unfortunately cases of paralysis due to wild virus in Malawi and Mozambique were detected having been imported from Pakistan. Outbreaks of circulating Vaccine Derived Polio Virus type 2 (cVDPV2) have expanded in the Eastern Mediterranean and African Region from October 2022 to February 2023. Measles, being one of the most contagious infections, requires high population immunity (>95 %) to impede transmission. In 1963, a measles vaccine became available. Finland was the first country to eradicate measles by using the 2 dose-measles vaccines. The region of the Americas was verified to have eliminated measles in 2000. The COVID-19 pandemic disrupted global vaccination activities. Vaccination coverage has fallen from 90 % to 50 % in western countries. Over 30 000 measles cases were reported from 40 WHO European Region members in 2023.

The nuclear localization signal of monkeypox virus protein P2 orthologue is critical for inhibition of IRF3-mediated innate immunity

ABSTRACT The Orthopoxvirus (OPXV) genus of the Poxviridae includes human pathogens variola virus (VARV), monkeypox virus (MPXV), vaccinia virus (VACV), and a number of zoonotic viruses. A number of Bcl-2-like proteins of VACV are involved in escaping the host innate immunity. However, little work has been devoted to the evolution and function of their orthologues in other OPXVs. Here, we found that MPXV protein P2, encoded by the P2L gene, and P2 orthologues from other OPXVs, such as VACV protein N2, localize to the nucleus and antagonize interferon (IFN) production. Exceptions to this were the truncated P2 orthologues in camelpox virus (CMLV) and taterapox virus (TATV) that lacked the nuclear localization signal (NLS). Mechanistically, the NLS of MPXV P2 interacted with karyopherin α-2 (KPNA2) to facilitate P2 nuclear translocation, and competitively inhibited KPNA2-mediated IRF3 nuclear translocation and downstream IFN production. Deletion of the NLS in P2 or orthologues significantly enhanced IRF3 nuclear translocation and innate immune responses, thereby reducing viral replication. Moreover, deletion of NLS from N2 in VACV attenuated viral replication and virulence in mice. These data demonstrate that the NLS-mediated translocation of P2 is critical for P2-induced inhibition of innate immunity. Our findings contribute to an in-depth understanding of the mechanisms of OPXV P2 orthologue in innate immune evasion.

Monkeypox: A Viral Zoonotic Disease of Rising Global Concern

Abstract Monkeypox (mpox) is a rare viral zoonotic disease, endemic to Central and West Africa, caused by the monkeypox virus, an orthopoxvirus similar to the variola virus (smallpox). Although sporadic travel-associated cases have historically occurred outside Africa, in May 2022, mpox began spreading globally in multiple nonendemic countries across several continents. In 2024, there has been an increase in globally reported confirmed cases of mpox and deaths from mpox, making it a public health emergency of international concern. The reasons for the unusual global spread are under investigation but likely relate to increased travel and waning population immunity to orthopoxviruses. Transmission now appears to be mainly through close, intimate contact, especially among men who have sex with men. Mpox is usually a self-limited disease. Although limited approved antiviral treatments are available, such as tecovirimat, which the European Medicines Agency approved in January 2022 for the treatment of mpox, their widespread availability and effectiveness in the current outbreak remain to be investigated. Public health control measures include surveillance, case identification/isolation, contact tracing, and targeted vaccination of contacts at high risk of exposure. However, challenges remain in curtailing the current unprecedented outbreak. Critical knowledge gaps include animal reservoir(s) responsible for initial spillover events, viral mutations that may enhance transmissibility, optimal diagnostics for noninvasive specimens, effective antiviral therapies, next-generation vaccines providing longer-term immunity, and building global capacity for outbreak response. This review summarizes the current literature on mpox virology, epidemiology, pathogenesis, clinical manifestations, diagnostics, treatment, prevention, and public health control measures. Ongoing investigation and research are needed to better understand mpox’s evolving epidemiology, pathogenicity, transmissibility, and ecology to guide strategies for containing the outbreak and preventing future global emergence.

Formulation of next-generation polyvalent vaccine candidates against three important poxviruses by targeting DNA-dependent RNA polymerase using an integrated immunoinformatics and molecular modeling approach

BackgroundPoxviruses comprise a group of large double-stranded DNA viruses and are known to cause diseases in humans, livestock animals, and other animal species. The Mpox virus (MPXV; formerly Monkeypox), variola virus (VARV), and volepox virus (VPXV) are among the prevalent poxviruses of the Orthopoxviridae genera. The ongoing Mpox infectious disease pandemic caused by the Mpox virus has had a major impact on public health across the globe. To date, only limited repurposed antivirals and vaccines are available for the effective treatment of Mpox and other poxviruses that cause contagious diseases. MethodsThe present study was conducted with the primary goal of formulating multi-epitope vaccines against three evolutionary closed poxviruses i.e., MPXV, VARV, and VPXV using an integrated immunoinformatics and molecular modeling approach. DNA-dependent RNA polymerase (DdRp), a potential vaccine target of poxviruses, has been used to determine immunodominant B and T-cell epitopes followed by interactions analysis with Toll-like receptor 2 at the atomic level. ResultsThree multi-epitope vaccine constructs, namely DdRp_MPXV (V1), DdRp_VARV (V2), and DdRp_VPXV (V3) were designed. These vaccine constructs were found to be antigenic, non-allergenic, non-toxic, and soluble with desired physicochemical properties. Protein-protein docking and interaction profiling analysis depicts a strong binding pattern between the targeted immune receptor TLR2 and the structural models of the designed vaccine constructs, and manifested a number of biochemical bonds (hydrogen bonds, salt bridges, and non-bonded contacts). State-of-the-art all-atoms molecular dynamics simulations revealed highly stable interactions of vaccine constructs with TLR2 at the atomic level throughout the simulations on 300 nanoseconds. Additionally, the outcome of the immune simulation analysis suggested that designed vaccines have the potential to induce protective immunity against targeted poxviruses. ConclusionsTaken together, formulated next-generation polyvalent vaccines were found to have good efficacy against closely related poxviruses (MPXV, VARV, and VPXV) as demonstrated by our extensive immunoinformatics and molecular modeling evaluations; however, further experimental investigations are still needed.

Two noncompeting human neutralizing antibodies targeting MPXV B6 show protective effects against orthopoxvirus infections

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.