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Protective #efficacy of a genetically modified attenuated #vaccinia virus #Tiantan strain against #monkeypox virus challenge in a small animal #model

  ABSTRACT Vaccinia virus (VACV) confers cross-protective immunity against monkeypox virus (MPXV), the causative agent of mpox, and has therefore been extensively exploited as a preventive vaccine . VACV Tiantan strain (VTT) is a second-generation smallpox vaccine used in China in the last century, and there are consistent efforts to minimize its virulence and ensure its best safety for potential clinical applications. In this study, an attenuated VACV rVTT△C12K2△A45 was constructed by deletion of gene segments related to virulence genes , host range genes, immune regulatory genes, and other functional genes from the VTT genome by genetic engineering. Attenuation characteristics of rVTT△C12K2△A45 were confirmed by smaller plaque size, lower replication capacity in various mammalian cell lines along with tests for neurotoxicity in mice , and lesion formation on rabbit skin . Immunization in BALB/c mice with rVTT△C12K2△A45 induced both anti-MPXV and anti-VACV neutralizing antibodies ...

#Mpox Multi-country external #situation #report no. 62, published 23 January 2026 (#WHO, summary)

  Highlights • All clades of monkeypox virus (MPXV) continue to circulate.  - Unless mpox outbreaks are rapidly contained and human-to-human transmission is interrupted, there is a risk of sustained community transmission .   • At the time of reporting, data from the WHO European Region for December 2025 had not yet been submitted; therefore, the information presented below does not include the European Region .  • In December 2025 , 31 countries across five WHO regions (European Region excluded) reported a total of 1040 new confirmed mpox cases , including six deaths (case fatality ratio [CFR] 0.6%).  - Of these cases, 78% were reported in the African Region .  - Four regions observed a decline in confirmed cases in December, compared to November 2025, while the Eastern Mediterranean Region reported more cases than the previous month.      • Fifteen countries in Africa reported active transmission of mpox in the last six weeks (7 Decemb...

The Emerging #Threat of #Monkeypox: An Updated #Overview

Abstract Monkeypox (MPOX) is an emerging zoonotic disease caused by monkeypox virus (MPXV), an orthopoxvirus closely related to smallpox . Initially confined to endemic regions in Central and West Africa , MPOX has recently gained global significance with outbreaks reported across multiple continents . MPXV is maintained in animal reservoirs but is increasingly transmitted from person to person , facilitated by close contact, respiratory droplets , and, in some cases, sexual transmission . Clinically, MPOX presents with fever, lymphadenopathy, and a characteristic vesiculopustular rash , though atypical manifestations have been observed in recent outbreaks, complicating diagnosis. Laboratory confirmation relies on molecular testing , while differential diagnosis must consider varicella, herpes, and other vesicular illnesses. Therapeutic options remain limited ; supportive care is the cornerstone of management, but antivirals such as tecovirimat and brincidofovir, as well as smallpox va...

A cocktail #vaccine with #monkeypox virus #antigens confers protection without selecting #mutations in potential immune evasion genes in the vaccinia WR strain challenge

ABSTRACT Faced with the global monkeypox outbreak, current vaccine development predominantly focuses on the mRNA platform despite its limitations in stability and long-term efficacy. Here, we engineered a recombinant vesicular stomatitis virus (rVSV)-vectored cocktail vaccine encoding four conserved monkeypox virus (MPXV) antigens (A35R, A29L, M1R, and B6R; >94% clade homology), leveraging the thermostable properties of the VSV platform validated for 4°C storage in Ebola vaccines. In BALB/c mice , this multi-antigen vaccine elicited a rapid humoral response with specific IgG detectable by day 7, effectively neutralized the virus, and induced a robust Th1/Th2 balanced cytokine response . Immunization conferred 100% survival against lethal vaccinia virus WR strain challenge , with undetectable viral loads in the lungs and serum , and sustained efficacy against secondary infection at 60 days. Histopathology confirmed minimal lung damage in vaccinated mice . Crucially, upon the successi...

#Mpox - Multi-country external #situation #report no. 61, published 22 December 2025 (#WHO, summary)

{Summary} Highlights     • All clades of monkeypox virus (MPXV) continue to circulate.  - Unless mpox outbreaks are rapidly contained and human-to-human transmission is interrupted , there is a risk of sustained community transmission .   • In November 2025, 48 countries across all WHO regions reported a total of 2150 new confirmed mpox cases , including five deaths ( case fatality ratio [CFR] 0.2%).  - About 68% of these cases were reported in the African Region .  - Four regions observed a decline in confirmed cases in November, compared to October 2025, while the European and Western Pacific regions reported more cases than the previous month.      • Nineteen countries in Africa reported active transmission of mpox in the last six weeks (2 November– 14 December 2025), with 1435 confirmed cases , including seven deaths (CFR 0.5%).  - Countries reporting the highest number of cases in this period are the Democratic Republic of the ...

#Mpox - Multi-country external #situation #report no. 60 published 8 December 2025 (#WHO, summary)

  {Summary} Highlights     • All clades of the monkeypox virus (MPXV) continue to circulate.  - When mpox outbreaks are not rapidly contained and human-to-human transmission is not interrupted, there is a risk of sustained community transmission .   • In October 2025, 44 countries , across all WHO regions, reported a total of 2501 new confirmed mpox cases , including 12 deaths (case fatality ratio [CFR] 0.5%).  - About 75% of these cases were reported in the African Region .  - All regions, apart from the South-East Asia Region observed a decline in confirmed cases in October, compared to September 2025.      • Twenty-one countries in Africa have reported active transmission of mpox in the last six weeks (12 October – 23 November 2025), with 1734 confirmed cases , including 10 deaths (CFR 0.6%) reported during this period.  - Countries reporting the highest number of cases in this period are the Democratic Republic of the Congo...

#UK: New #mpox #strain identified in #England (#UKHSA, Dec. 8 '25)

  Latest update The UK Health Security Agency (UKHSA) has identified a new recombinant mpox virus in England in an individual who had recently travelled to Asia .   -- Genomic sequencing showed that the mpox genome contained elements of clade Ib and IIb mpox .  -- This is not unexpected as both clades are circulating , but highlights the continued potential for mpox virus to evolve and the importance of continued genomic surveillance.     -- UKHSA continues to assess the significance of the strain.   Dr Katy Sinka, Head of Sexually Transmitted Infections at UKHSA, said:    '' Our genomic testing has enabled us to detect this new mpox strain . It’s normal for viruses to evolve, and further analysis will help us understand more about how mpox is changing.   '' Although mpox infection is mild for many, it can be severe . Getting vaccinated is a proven effective way to protect yourself against severe disease, so please make su...

Broader #transmission of #mpox due to clade Ib #MPXV – #Global #situation (#WHO D.O.N., Dec. 5 '25, summary)

  Situation at a glance The purpose of this report is to raise awareness about the local transmission of clade Ib monkeypox virus (MPXV) among men who have sex with men (MSM) in countries previously unaffected or to date reporting only cases linked to travel.  This report summarizes recent epidemiological developments , response activities, and the associated global public health risk .  The second declaration of a public health emergency of international concern (PHEIC) for mpox was lifted on 5 September 2025.  As both MPXV clades I and II and their subclades continue to circulate globally, leading to substantial outbreaks in African countries , WHO continues to advise emergency preparedness and response activities .  Multiple modes of transmission underlie ongoing virus circulation , with sexual contact remaining the primary amplifier of transmission in most settings.  Since 5 September 2025, several countries across four of six WHO regions have confirmed...

Long-term consequences of #monkeypox virus #infection or modified vaccinia virus Ankara #vaccination in #Belgium ...

  Summary Background Given the continued global circulation of monkeypox virus (MPXV), we aimed to assess the long-term clinical consequences of MPXV infection and the continued presence of the virus in saliva, semen, and the anorectum . We also aimed to compare long-term antibody dynamics after MPXV infection with modified vaccinia Ankara–Bavarian Nordic (MVA-BN) vaccination. Methods In this mixed retrospective and prospective cohort study, adults with acute MPXV infection at the Institute of Tropical Medicine (Antwerp, Belgium) were enrolled in a clinical registry (MPX-COHORT) from May 13, 2022, with follow-up at 1 month after infection. On Oct 3, 2022, we initiated a long-term follow-up study (POQS-FU-PLUS) to extend follow-up of people with mpox and to establish a parallel cohort of adults who received MVA-BN vaccination between Aug 3, 2022, and Jan 4, 2023. Participants were eligible for the second cohort if they received two doses of MVA-BN, unless they had previous smallpox ...

Simultaneous #outbreaks of #Ebola, #cholera, #mpox, and #measles in #DRC in 2025

  {Excerpt} On Sept 4, 2025, the DR Congo Government and Ministry of Health announced a new Ebola virus disease outbreak in the Bulape health zone (Kasai province), marking the end of over 15 years without any reported cases of Ebola virus disease in this region . As of Sept 14, 2025, there were 35 confirmed Ebola virus disease cases and 16 deaths , representing a case fatality rate of 45·7%.1,2 This unexpected resurgence in a region with insufficient preparedness capacity raises serious concerns about potential regional spread, including towards neighbouring Angola. At the same time, DR Congo is experiencing one of the most severe cholera outbreaks of the past decade , with a total of 48 139 cases and 1443 deaths reported between Jan 1 and Aug 24, 2025, resulting in a case fatality rate of 3%.3 By epidemiological week 33, high case fatality rates were reported in the provinces of Kwilu (76 cases, 26 deaths; 44%), Sankuru (42 cases, 6 deaths; 14%), and Equateur (224 cases, 19 death...

#Mpox Multi-country external #situation #report no. 59 published 30 October 2025 (#WHO, summary)

  Highlights     • This Situation report will now be published monthly.  • All clades of the monkeypox virus (MPXV) continue to circulate. When mpox outbreaks are not rapidly contained and human-to-human transmission is not interrupted, there is a risk of sustained community transmission.   • In September 2025, 42 countries , across all WHO regions, reported a total of 3135 confirmed cases , including 12 deaths (case fatality ratio [CFR] 0.4%). More than 80% of these cases were reported in the African Region . Four regions (African Region, Eastern Mediterranean Region, Region of the Americas, and the Western Pacific) observed a declining trend in confirmed cases reported per month, while the European and South-East Asian regions observed an increase in cases in September 2025. • Seventeen countries in Africa have experienced ongoing active transmission of mpox in the last six weeks (14 Sep – 19 Oct 2025), with 2862 confirmed cases, including 17 deaths (CFR ...

Latest #update on Clade Ib #mpox - #UKHSA reminds eligible groups to come forward for mpox #vaccination.

  Last updated 27 October 2025 Latest update UKHSA is aware of small numbers of locally-acquired cases of clade Ib mpox in the USA , Spain, Italy , the Netherlands and Portugal which have no connection to countries with known clade Ib mpox transmission.   This suggests there is now community transmission of clade Ib mpox globally . Most of the new cases identified in Europe and the USA have been in gay, bisexual and other men who have sex with men , a population in which clade Ib mpox transmission has not previously been observed.   Mpox is usually a mild infection , and clade Ia and Ib mpox are no longer classified as a high-consequence infectious disease (HCID). However, it can be severe in some cases.  The UK has a routine mpox vaccination programme in place for eligible groups, including those who:   -- have multiple sexual partners   -- have group sex   -- visit sex-on-premises venues   Studies show that the vacc...

#Mpox #Epidemics: A Call to Restore Humanity’s Lost Herd #Immunity to #Orthopoxviruses

  Abstract Global efforts to eradicate smallpox—an Orthopoxvirus infection—began in the mid-20th century, with the last naturally occurring case reported in 1977. This was achieved through global solidarity efforts that expanded the smallpox eradication vaccination program . Approximately 50 years following the cessation of mass smallpox vaccination and in the absence of access to a sustainable boosting program , the population immunologically naĂ¯ve to Orthopoxviruses has increased significantly. With increasing global movements and travels, we argue that the emergence of two back-to-back yet distinct mpox epidemics in the 21st century is a sign of humanity’s lost herd immunity to Orthopoxviruses. This needs concerted efforts to restore. Source: Viruses,  https://www.mdpi.com/1999-4915/17/9/1257 ____

Evolving #Threats: Adaptive Mechanisms of #Monkeypox Virus (MPXV) in the 2022 Global #Outbreak and Their Implications for #Vaccine Strategies

  Abstract Monkeypox virus (MPXV) experienced an unprecedented global outbreak in 2022, characterized by a significant departure from historical patterns: a rapid spread of the epidemic to more than 110 non-traditional endemic countries , with more than 90,000 confirmed cases; a fundamental shift in the mode of transmission , with human-to-human transmission (especially among men who have sex with men (MSM)) becoming the dominant route (95.2%); and genetic sequencing revealing a key adaptive mutation in a novel evolutionary branch ( Clade IIb ) that triggered the outbreak. These features highlight the significant evolution of MPXV in terms of host adaptation, transmission efficiency, and immune escape ability . The aim of this paper is to provide insights into the viral adaptive evolutionary mechanisms driving this global outbreak, with a particular focus on the role of immune escape (e.g., novel mechanisms of M2 proteins targeting the T cell co-stimulatory pathway) in enhancing vi...

The Trans-Kingdom #Spectrum of #Mpox-like Lesion Pustules of Suspect #Patients in the Mpox Clade Ib #Outbreak in Eastern #DRC

  Abstract During infectious disease outbreaks, acquiring genetic data across various kingdoms offers essential information to tailor precise treatment methodologies and bolster clinical, epidemiological, and public health awareness. Metagenomics sequencing has paved the way for personalized treatment approaches and streamlined the monitoring process for both co-infections and opportunistic infections. In this study, we conducted long-read metagenomic DNA sequencing on mpox-like lesion pustules from six suspected patients who were positive and confirmed to be infected with MPXV during the MPXV subclade Ib outbreak in the Eastern Democratic Republic of the Congo. The sequenced data were taxonomically classified as bacterial, fungal, and viral in composition . Our results show a wide spectrum of microorganisms present in the lesions . Bacteria such as Corynebacterium amycolatum, Gardnerella vaginalis, Enterococcus faecium, Enterobacter clocae, Staphylococcus epidermidis, and Stenotro...

#Mpox Multi-country external #situation #report no. 57 published 28 August 2025 (#WHO, summary)

  Highlights     • All clades of monkeypox virus (MPXV) continue to circulate in several countries.  - When mpox outbreaks are not rapidly contained and human-to-human transmission is not interrupted, they continue to pose a risk of sustained community transmission .  - Since the last edition of this report , one country, Senegal , has reported mpox for the first time . Efforts to identify the clade are underway.  • Furthermore, TĂ¼rkiye has reported cases of mpox due to clade Ib MPXV for the first time and the Democratic Republic of Congo has reported its first cases of mpox due to clade IIb MPXV.   • In July 2025, 47 countries in five (out of six) WHO regions reported a total of 3924 confirmed cases , including 30 deaths (case fatality ratio [CFR] 0.8% ).  - The South-East Asian and Western Pacific regions reported an increase in cases in July 2025, while the African Region, European Region and the Region of the Americas reported a decrease....

The #pathogenicity and multi-organ proteomic profiles of #Mpox virus #infection in SIVmac239-infected rhesus #macaques

  Abstract Mpox poses a heightened risk of severe disease and mortality among individuals with HIV , yet the molecular mechanisms and immunopathology underlying multi-organ damage caused by the mpox virus (MPXV), particularly in the context of HIV co-infection, remain poorly understood. Here, we observe increased MPXV replication, more extensive skin lesions, and impaired humoral and cellular immune responses in SIV-MPXV co-infected rhesus macaques compared to those infected with MPXV alone. Multi-organ proteomic and phosphoproteomic analyses reveals upregulation of proteins involved in immune and inflammatory pathways in skin lesions and across multiple organs, especially in immune-related tissues. Abnormal activation of DNA replication and cell cycle signaling pathways , which may contribute to enhanced viral replication, is evident in both MPXV and SIV-MPXV co-infected groups. CDK4/6 may present a potential therapeutic target to suppress MPXV replication. These comprehensive pro...

#Mpox: disease #manifestations and therapeutic #development

  ABSTRACT Mpox, caused by monkeypox virus (MPXV) infection, has emerged as a significant global health threat . The World Health Organization (WHO) has twice declared a Public Health Emergency of International Concern for mpox: first for the 2022–2023 global outbreak and subsequently for concurrent outbreaks in Africa. Beyond MPXV, other members of the Orthopoxvirus genus also pose growing risks of zoonotic spillover , with the potential to jump from animal reservoirs to humans . Clinically, mpox is distinguished from other Orthopoxvirus infections by its propensity to cause severe systemic manifestations alongside localized skin lesions , disproportionately affecting vulnerable groups such as children, pregnant women, and immunocompromised individuals . Although vaccines are available, effective therapeutics are equally essential in combating the mpox crisis. Current antiviral agents , including tecovirimat and brincidofovir , have demonstrated uncertain or disappointing efficacy...

#Mpox - Multi-country external #situation #report no. 56 published 31 July 2025 (#WHO, edited)

  {Excerpt} Highlights -- All clades of monkeypox virus (MPXV) continue to circulate in several countries.  - When mpox outbreaks are not rapidly contained and human-to-human transmission is not interrupted, they continue to pose a risk of sustained community transmission .   -- Since the last edition of this report, one new country, the Gambia , has reported an mpox case for the first time.  - Genomic sequencing analysis has identified clade IIb MPXV.  -- Furthermore, Mozambique, has reported cases of mpox due to clade Ib MPXV for the first time.   -- Twenty-one countries in Africa have reported ongoing mpox transmission in the past six weeks.  - Clade IIb MPXV continues to be reported in West Africa, while Central African countries report both clade Ia and clade Ib MPXV, and East African countries report clade Ib MPXV.  -- The recent overall downward trend of confirmed cases across the continent is driven by the decline in cases in Sie...

Emergence of Clade Ib #Monkeypox Virus—Current State of #Evidence

Abstract Mpox was first identified against the backdrop of the smallpox eradication campaign. Monkeypox virus (MPXV), the causative agent of mpox, has been maintained in animal reservoirs in the forested regions of West and Central Africa as 2 distinct clades ; clade I has historically caused more severe infection in Central Africa than clade II , historically found in West Africa . However, rapid reemergence and spread of both MPXV clades through novel routes of transmission have challenged the known characteristics of mpox. We summarize mpox demographic distribution , clinical severity , and case-fatality rates attributed to genetically distinct MPXV subclades and focus on MPXV clade Ib, the more recently identified subclade. Broad worldwide assistance will be necessary to halt the spread of both MPXV clades within mpox endemic and nonendemic regions to prevent future outbreaks. Source: US Centers for Disease Control and Prevention,  https://wwwnc.cdc.gov/eid/article/31/8/24-1551...