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Pan-genome and reverse vaccinology for a multi-epitope vaccine against circulating post-2022 Monkeypox virus strains.

BACKGROUND: Since the 2022 outbreak, the number of Monkeypox cases worldwide has been increasing at an alarming rate. As of August 2024, app … s a broad-spectrum multi-epitope vaccine that elicits humoral and adaptive immune responses against Monkeypox virus (MPXV) infection. METHODS: During an outbreak, a pan-genome-based reverse vaccinology approach can offer rapid, practical solutions to enduring problems in experimental vaccine design. The method involved screening 16 monkeypox genomes to identify …

Genomic characteristics of the first five monkeypox virus clade Ib cases in Thailand: August 2024-March 2025.

Following the emergence of monkeypox virus clade Ib in the Democratic Republic of the Congo in August 2024, the World Health Organization declared a public health emergency of international concern because of sustained transmission and international spread. We characterized the first clade Ib cases detected in Thailand between August 2024 and March 2025 and assessed their phylogenetic relationships. Whole-genome sequencing was performed from lesion swabs of suspected cases. Phylogenetic analysis, incorporating clade Ia (DQ011155.1) and global clade Ib sequences from GISAID, confirmed all Thai …

Сопоставление двух- и трёхдозных вакцин против вируса MVA-BN Mpox на иммунитете от вируса обезьяны.

В 2022 году глобальная вспышка клифа IIb mpox стала поворотным пунктом в работе общественного здравоохранения с оксивирусами. Первичная вакцина, имеющаяся для предотвращения заболевания мпоксом, модифицирована вакцина Анкары из Баварии-Нордика (MVA-BN). Ранее мы сообщали о неуязвимом и слабопоглощающем антителе против Mpox, вызванном MVA-BN. В этом исследовании мы расширили эти знания, используя микронейтрализацию для измерения обезьянопокс-вируса (MPXV), нейтрализующего титеры, и множественную иммуномассию для оценки титров и аномалий IgG против восьми антигенов MPXV и двух антигенов вакцины.

Совпадение в аннотации оригинала
The 2022 global outbreak of clade IIb mpox represented a turning point in public health's handling of poxviruses. The primary vaccine availa … In this study, we expanded upon this knowledge by employing a microneutralization assay to measure monkeypox virus (MPXV) neutralizing titers and a multiplexed immunoassay to assess IgG titers and avidity against eight MPXV antigens and two vaccinia antigens. Through a machine learning analysis, we uncovered that MVA-BN vaccinees without prior smallpox vaccinati …

A targeted tiled amplicon sequencing approach for clade and subclade level differentiation of monkeypox virus from wastewater.

Wastewater-based surveillance (WBS) has modernized in recent years and emerged as an important tool for the monitoring of viral pathogens, including monkeypox virus (MPXV). Here we describe a novel targeted amplicon sequencing method developed for clade and subclade characterization of MPXV from municipal wastewater. This new method addresses the limitations of PCR-based methods and the challenges of sequencing a pathogen displaying low viral load in municipal wastewater samples. A tiled amplicon scheme composed of 11 primer pairs targeting a 4.2 kb portion of the inverted terminal repeat (ITR…

Immune Responses and Protective Efficacy of Nanoemulsion-Adjuvanted Monkeypox Virus Recombinant Vaccines Against Lethal Challenge in Mice.

The ongoing global monkeypox outbreak since 2022 has highlighted the urgent need for vaccine development. Current vaccination strategies rely on cross-protective immunity provided by orthopoxvirus-based live-attenuated vaccines. However, these vaccines not only exhibit suboptimal efficacy against monkeypox virus (MPXV) but also raise safety concerns, particularly given the significant global overlap between MPXV infections and HIV. Owing to their superior safety profile and accessibility, recombinant subunit vaccines represent a highly promising platform for monkeypox vaccine development. In t…

Point-of-care detection of Monkeypox virus clades using high-performance upconversion nanoparticle-based lateral flow assay.

There is an urgent need for a point-of-care testing (POCT) method in developing and underserved regions to distinguish between two Monkeypox virus (MPXV) clades, given their varying transmissibility and clinical manifestations. In this paper, we target the specific complement protein gene fragment of two MPXV clades and construct a high-performance upconversion nanoparticles-based lateral flow assay (UCNPs-based LFA) with double T-lines and a shared C-line. This enables qualitative and quantitative dual-mode detection when combined with a smartphone and a benchtop fluorescence analyzer. The de…

Monkeypox Virus Neutralizing Antibodies at Six Months from Mpox Infection: Virologic Factors Associated with Poor Immunologic Response.

A natural monkeypox virus infection may not induce sufficient neutralizing antibody responses in a subset of healthy individuals. The aim of this study was to evaluate monkeypox virus-neutralizing antibodies six months after infection and to assess the virological factors predictive of a poor immunological response. Antibodies were assessed using a plaque reduction neutralization test at six months from mpox infection; mpox cutaneous, oropharyngeal, and anal swabs, semen, and plasma samples were tested during infection. Overall, 95 people were included in the study; all developed detectable an…

CRISPR/Cas12a antifouling nanocomposite electrochemical biosensors enable amplification-free detection of Monkeypox virus in complex biological fluids.

The escalating global threat of infectious diseases, including monkeypox virus (MPXV), necessitates advancements in point-of-care diagnostics, moving beyond the constraints of conventional methods tethered to centralized laboratories. Here, we introduce multiple CRISPR RNA (crRNA)-based biosensors that can directly detect MPXV within 35 minutes without pre-amplification, leveraging the enhanced sensitivity and antifouling attributes of the BSA-based nanocomposite. Multiple crRNAs, strategically targeting diverse regions of the F3L gene of MPXV, are designed and combined to amplify Cas12a activ…

Real-time PCR assay to detect the novel Clade Ib monkeypox virus, September 2023 to May 2024.

Monkeypox virus (MPXV) is an emerging zoonotic pathogen with complex epidemiology necessitating rapid diagnosis and distinguishing between clades and subclades. The emerging Clade Ib lacks the genomic region used in the Clade I-specific assay from the Centers for Disease Control and Prevention. We report an MPXV real-time PCR to specifically detect Clade Ib. The assay demonstrated proficient sensitivity and specificity in 92 samples and can be included along other TaqMan-based assays to detect MPXV and distinguish between clades and subclades.

Bioinformatic identification of monkeypox virus phylogenetic gene trees that are representative of its whole-genome phylogenetic tree.

Phylogenetic analysis based on whole-genome sequences is the gold standard for monkeypox virus (MPXV) phylogeny. However, genomic epidemiology capability and capacity are lacking or limited in resource poor countries of sub-Saharan Africa. Therefore, these make real-time genome surveillance of MPXV virtually impossible. We hypothesized that phylogenetic analysis based on single, conserved genes will produce phylogenetic tree topology consistent with MPXV whole-genome phylogeny, thus serving as a reliable proxy to phylogenomic analysis. In this study, we analyzed 62 conserved MPXV genes and sho…

Evaluation of monkeypox- and vaccinia-virus neutralizing antibodies before and after smallpox vaccination: A sero-epidemiological study.

Since May 2022, several countries outside of Africa experienced multiple clusters of monkeypox virus (MPXV)-associated disease. In the present study, anti-MPXV and anti-vaccinia virus (VACV) neutralizing antibody responses were evaluated in two cohorts of subjects from the general Italian population (one half born before the WHO-recommended end of smallpox vaccination in 1980, the other half born after). Higher titers (either against MPXV or VACV) were observed in the cohort of individuals born before the interruption of VACV vaccination. An association between VACV and MPXV antibody levels wa…

Systematic evaluation of the induction of efficient neutralizing antibodies by recombinant multicomponent subunit vaccines against monkeypox virus.

Mpox (formerly known as monkeypox), which has symptoms similar to smallpox, is a zoonotic disease caused by the monkeypox virus (MPXV). From 1 January 2022 to 31 March 2024, 117 countries, territories, or areas reported 95,226 laboratory-confirmed cases of Mpox (including 185 deaths) to the World Health Organization. However, as there is no licensed specific MPXV vaccine available globally, the vaccines currently used for mpox prevention are mostly smallpox vaccines. Thus, the rapid development of safe and effective vaccines is urgently required. In the present study, the key MPXV proteins A35…

Monkeypox virus-induced upregulation of interleukin-10 signaling: could epigenetics be involved in long-term viral persistence?

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Machine learning and classical MD simulation to identify inhibitors against the P37 envelope protein of monkeypox virus.

Monkeypox virus (MPXV) outbreak is a serious public health concern that requires international attention. P37 of MPXV plays a pivotal role in DNA replication and acts as one of the promising targets for antiviral drug design. In this study, we intent to screen potential analogs of existing FDA approved drugs of MPXV against P37 using state-of-the-art machine learning and computational biophysical techniques. AlphaFold2 guided all-atoms molecular dynamics simulations optimized P37 structure is used for molecular docking and binding free energy calculations. Similar to members of Phospholipase-D…

Rapid detection of monkeypox virus using a CRISPR-Cas12a mediated assay: a laboratory validation and evaluation study.

BACKGROUND: The 2022 outbreak of mpox (formerly known as monkeypox) led to the spread of monkeypox virus (MPXV) in over 110 countries, demanding effective disease management and surveillance. As current diagnostics rely largely on centralised laboratory testing, our objective was to develop a simple rapid point-of-care assay to detect MPXV in clinical samples using isothermal amplification coupled with CRISPR and CRISPR-associated protein (Cas) technology. METHODS: In this proof-of-concept study, we developed a portable isothermal amplification CRISPR-Cas12a-based assay for the detection of M…

Letter to Editor: Antiviral activities of ginseng and its potential benefit against monkeypox virus: A mini review.

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Monkeypox virus (MPXV): A Brief account of global spread, epidemiology, virology, clinical features, pathogenesis, and therapeutic interventions.

The largest monkeypox virus (MPXV) outbreak of the 21st century occurred in 2022, which caused epidemics in many countries. According to WHO, physical contact with infected persons, contaminated surfaces, or affected animals might be a source of this virus transmission. A febrile sickness including few symptoms found in MPX disease. Skin rash, lesions, fever, headache, fatigue, and muscle aches symptoms were observed commonly for this disease. Animal and in vitro, studies have shown that the antiviral medications cidofovir and brincidofovir are effective against MPXV. The first-generation vacc…

Characterization of immune response against monkeypox virus in cohorts of infected patients, historic and newly vaccinated subjects.

Monkeypox virus (MPXV) is a zoonotic disease endemic in the rainforest countries of Central and West Africa. Understanding the immune response in zoonosis is fundamental to prevent and contrast viral spreading. MPXV is a close relative of Variola (smallpox) virus and vaccination with vaccinia virus gives approximatively 85% of protection against MPXV. With the emergence of the recent MPXV outbreak, JYNNEOS vaccine has been proposed to individuals at high-risk of exposure. Comparative data on MPXV immune response in vaccinated or infected subjects are still limited. Here we set-up an immunofluo…