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Expert Opin Biol Ther 2023 Sep 25:1-17. Epub 2023 Sep 25.

Department of Neurosurgery, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.

Introduction: Many pediatric patients with malignant tumors continue to suffer poor outcomes. The current standard of care includes maximum safe surgical resection followed by chemotherapy and radiation which may be associated with considerable long-term morbidity. The emergence of oncolytic virotherapy (OVT) may provide an alternative or adjuvant treatment for pediatric oncology patients. Read More

Nat Biomed Eng 2023 Sep 25. Epub 2023 Sep 25.

Lab of Viral Zoonotics, Department of Veterinary Medicine, University of Cambridge, Cambridge, UK.

The threat of spillovers of coronaviruses associated with the severe acute respiratory syndrome (SARS) from animals to humans necessitates vaccines that offer broader protection from sarbecoviruses. By leveraging a viral-genome-informed computational method for selecting immune-optimized and structurally engineered antigens, here we show that a single antigen based on the receptor binding domain of the spike protein of sarbecoviruses elicits broad humoral responses against SARS-CoV-1, SARS-CoV-2, WIV16 and RaTG13 in mice, rabbits and guinea pigs. When administered as a DNA immunogen or by a vector based on a modified vaccinia virus Ankara, the optimized antigen induced vaccine protection from the Delta variant of SARS-CoV-2 in mice genetically engineered to express angiotensin-converting enzyme 2 and primed by a viral-vector vaccine (AZD1222) against SARS-CoV-2. Read More

Biochemistry (Mosc) 2023 Jun;88(6):823-841

Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991, Russia.

Cancer virotherapy is an alternative therapeutic approach based on the viruses that selectively infect and kill tumor cells. Vaccinia virus (VV) is a member of the Poxviridae, a family of enveloped viruses with a large linear double-stranded DNA genome. The proven safety of the VV strains as well as considerable transgene capacity of the viral genome, make VV an excellent platform for creating recombinant oncolytic viruses for cancer therapy. Read More

Biotechnol Bioeng 2023 Sep 25. Epub 2023 Sep 25.

State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, China.

The messenger RNA (mRNA) 5'-cap structure is indispensable for mRNA translation initiation and stability. Despite its importance, large-scale production of capped mRNA through in vitro transcription (IVT) synthesis using vaccinia capping enzyme (VCE) is challenging, due to the requirement of tedious and multiple pre-and-post separation steps causing mRNA loss and degradation. Here in the present study, we found that the VCE together with 2'-O-methyltransferase can efficiently catalyze the capping of poly dT media-tethered mRNA to produce mRNA with cap-1 structure under an optimized condition. Read More

Front Microbiol 2023 7;14:1243523. Epub 2023 Sep 7.

Diagnostic Systems Division, United States Army Medical Research Institute of Diseases, Frederick, MD, United States.

Human monkeypox (mpox) has recently become a global public health emergency; however, assays that detect mpox infection are not widely available, largely due to cross-reactivity within the genus. Immunoassay development was largely confined to researchers who focus on biothreats and endemic areas (Central and West Africa) until the 2022 outbreak. As was noted in the COVID-19 pandemic, antigen detection assays, integrated with molecular assays, are necessary to help curb the spread of disease. Read More

Nat Commun 2023 Sep 23;14(1):5948. Epub 2023 Sep 23.

Research and Development, UK Health Security Agency, Porton Down, Wiltshire, UK.

In early 2022, a cluster of monkeypox virus (MPXV) infection (mpox) cases were identified within the UK with no prior travel history to MPXV-endemic regions. Subsequently, case numbers exceeding 80,000 were reported worldwide, primarily affecting gay, bisexual, and other men who have sex with men (GBMSM). Public health agencies worldwide have offered the IMVANEX Smallpox vaccination to these individuals at high-risk to provide protection and limit the spread of MPXV. Read More

Nat Commun 2023 Sep 22;14(1):5925. Epub 2023 Sep 22.

China National Biotec Group Company Limited (CNBG), Beijing, China.

The recent outbreaks of mpox have raised concerns over the need for effective vaccines. However, the current approved vaccines have either been associated with safety concerns or are in limited supply. mRNA vaccines, which have shown high efficacy and safety against SARS-CoV-2 infection, are a promising alternative. Read More

Microbiol Spectr 2023 Sep 22:e0159823. Epub 2023 Sep 22.

Israel Institute for Biological Research, Ness Ziona, Israel.

Members of the genus can cause severe infections in humans. Global vaccination against smallpox, caused by the variola virus, resulted in the eradication of the disease in 1980. Shortly thereafter, vaccination was discontinued, and as a result, a large proportion of the current population is not protected against orthopoxviruses. Read More

Microbiol Spectr 2023 Sep 22:e0168423. Epub 2023 Sep 22.

Department of Dermatology, University of Rochester Medical Center , Rochester, New York, USA.

Individuals with atopic dermatitis (AD) are highly colonized by and are more susceptible to severe viral complications. We hypothesized that secreted virulence factors may alter keratinocyte biology to enhance viral susceptibility through disruption of the skin barrier, impaired keratinocyte differentiation, and/or inflammation. To address this hypothesis, human keratinocytes were exposed to conditioned media from multiple strains that vary in virulence factor production (USA300, HG003, and RN4220) or select purified virulence factors. Read More

J Virol 2023 Sep 22:e0072323. Epub 2023 Sep 22.

UMR ASTRE, CIRAD, INRAE, University of Montpellier (I-MUSE) , Montpellier, France.

Lumpy skin disease (LSD) virus, a ruminant poxvirus of the genus, is the etiologic agent of an economically important cattle disease categorized as a notifiable disease by the World Organisation for Animal Health. The large and complex enveloped LSD virus (LSDV) particle encloses a double-stranded linear DNA genome of 151 kbp, comprising 156 predicted ORFs, together with a variety of proteins that are not yet identified. In parallel with a recent widespread expansion of LSD, many LSDV whole genomes have been sequenced, but knowledge on protein composition of the LSDV particle remains missing. Read More

mBio 2023 Sep 20:e0188723. Epub 2023 Sep 20.

Instituto de Biofísica Carlos Chagas Filho , Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.

Vaccinia virus is the active component of all modern smallpox vaccines after the mid-20th century, but it is uncertain to what extent cowpox, vaccinia, and horsepox viruses were used to produce vaccines before then. Genome sequences of six smallpox vaccines used in the United States between 1850 and 1902, namely VK01, VK02, VK05, VK08, VK12, and Mulford_1902 vaccines, revealed >99.5% similarity with a 1976 strain of horsepox in the genome core. Read More

Mol Ther Oncolytics 2023 Sep 31;30:301-315. Epub 2023 Aug 31.

Institute of BioInnovation Research, Kolon Life Science, Seoul 07793, Republic of Korea.

Oncolytic viruses are of significant clinical interest due to their ability to directly infect and kill tumors and enhance the anti-tumor immune response. Previously, we developed KLS-3010, a novel oncolytic virus derived from the International Health Department-White (IHD-W) strain vaccinia virus, which has robust tumoricidal effects. In the present study, we generated a recombinant oncolytic virus, KLS-3020, by inserting three transgenes (hyaluronidase [PH-20], interleukin-12 [IL-12], and soluble programmed cell death 1 fused to the Fc domain [sPD1-Fc]) into KLS-3010 and investigated its anti-tumor efficacy and ability to induce anti-tumor immune responses in CT26. Read More

Signal Transduct Target Ther 2023 Sep 15;8(1):350. Epub 2023 Sep 15.

Department of Laboratory Medicine, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China.

The ongoing pandemic caused by mpox virus (MPXV) has become an international public health emergency that poses a significant threat to global health. The vaccinia virus Tiantan strain (VTT) was used to vaccinate against smallpox in China 42 years ago. It is urgent to assess the level of immunity to smallpox in individuals vaccinated 43 or more years ago and evaluate their immunological susceptibility to MPXV. Read More

Cancer Manag Res 2023 5;15:977-978. Epub 2023 Sep 5.

[This retracts the article DOI: 10.2147/CMAR.S273072. Read More

Lancet Infect Dis 2023 Sep 4. Epub 2023 Sep 4.

Blizard Institute and SHARE Collaborative, Queen Mary University of London, London, UK; Department of Infection and Immunity, Barts Health NHS Trust, London, UK. Electronic address:

Background: Since May, 2022, a large global outbreak of human mpox (formerly known as monkeypox) has predominantly affected men who have sex with men. The strain responsible, Clade IIb, has mutated substantially from precursors originating from the 2017-18 outbreak in Nigeria. Immunity to smallpox, another orthopoxvirus, via previous infection or vaccination provides lifelong immunity. Read More

MMWR Morb Mortal Wkly Rep 2023 Sep 8;72(36):992-996. Epub 2023 Sep 8.

The effectiveness of 1 dose of JYNNEOS vaccine (modified vaccinia Ankara vaccine, Bavarian Nordic) against hospitalization for mpox (caused by Monkeypox virus), has been demonstrated; however, the impact of 2 doses on hospitalization risk, especially among persons infected with HIV, who are at higher risk for severe disease, is an important factor in evaluating vaccine effectiveness against mpox disease severity and Monkeypox virus infection. Surveillance data collected by the California Department of Public Health were used to evaluate whether receipt of 2 doses of JYNNEOS vaccine reduced the odds of hospitalization among persons with mpox. The odds of hospitalization among persons with mpox who had received 1 or 2 JYNNEOS doses were 0. Read More

Microb Pathog 2023 Oct 1;183:106328. Epub 2023 Sep 1.

Animal Diseases and Public Health Engineering Research Center of Henan Province, Luoyang, 471000, China. Electronic address:

Vaccination is principally used to control and treat porcine reproductive and respiratory syndrome virus (PRRSV) infection. This study investigated immunogenicity and protective efficacy of heterologous prime-boost regimens in pigs, including recombinant DNA and vaccinia virus vectors coexpressing PRRSV European genotype (EU) isolate GP3 and GP5: group A, pVAX1-EU-GP3-GP5 prime and rddVTT-EU-GP3-GP5 boost; group B, rddVTT-EU-GP3-GP5 prime and pVAX1-EU-GP3-GP5 boost; group C, empty vector pVAX1; group D, E3L gene-deleted vaccinia virus E3L- VTT. Vaccine efficacy was tested in an EU-type PRRSV (Lelystad virus strain) challenge pig model based on evaluating PRRSV-specific antibody responses, neutralizing antibodies, cytokines, T lymphocyte proliferation, CD4 and CD8 T lymphocytes, clinical symptoms, viremia and tissue virus loads. Read More

mBio 2023 Aug 30:e0113523. Epub 2023 Aug 30.

Department of Molecular Biology and Biochemistry, University of California Irvine , Irvine, California, USA.

Vaccinia virus, the prototypical poxvirus and smallpox/monkeypox vaccine, has proven a challenging entity for structural biology, defying many of the approaches leading to molecular and atomic models for other viruses. Via a combination of deep learning and cross-linking mass spectrometry, we have developed an atomic-level model and an integrated processing/assembly pathway for a structural component of the vaccinia virion, protein P4a. Within the pathway, proteolytic separation of the C-terminal P4a-3 segment of P4a triggers a massive conformational rotation within the N-terminal P4a-1 segment that becomes fixed by disulfide-locking while removing a steric block to trimerization of the processing intermediate P4a-1+2. Read More

Mol Ther Oncolytics 2023 Sep 20;30:103-116. Epub 2023 Jul 20.

Transgene, 67405 Illkirch-Graffenstaden, France.

TG6002 is an oncolytic vaccinia virus expressing FCU1 protein, which converts 5-fluorocytosine into 5-fluorouracil. The study objectives were to assess tolerance, viral replication, 5-fluorouracil synthesis, and tumor microenvironment modifications to treatment in dogs with spontaneous malignant tumors. Thirteen dogs received one to three weekly intratumoral injections of TG6002 and 5-fluorocytosine. Read More

Viruses 2023 Aug 15;15(8). Epub 2023 Aug 15.

Department of Dermatology, University Hospital Muenster, University of Muenster, 48149 Muenster, Germany.

Monkeypox (mpox), a former rare viral zoonosis, has increasingly made it into the public eye since the major outbreak that started in May 2022. Mpox presents with skin lesions that change over time and go through different stages (macular, papular, pustular, and early and late ulceration). In this study, we evaluated skin biopsies of all stages. Read More

Viruses 2023 Aug 15;15(8). Epub 2023 Aug 15.

Vaccine Research Center, National Institutes of Health, 40 Convent Drive, Bethesda, MD 20892, USA.

Smallpox was eradicated in less than 200 years after Edward Jenner's practice of cowpox variolation in 1796. The forty-three years of us living free of smallpox, beginning in 1979, never truly separated us from poxviruses. The recent outbreak of monkeypox in May 2022 might well warn us of the necessity of keeping up both the scientific research and public awareness of poxviruses. Read More

Sci Rep 2023 Aug 25;13(1):13913. Epub 2023 Aug 25.

Department of Biochemistry, Kyushu University Graduate School of Medical Sciences, 3-1-1 Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan.

Although methods for sequencing library preparation from double-stranded DNA are well established, those from single-stranded DNA (ssDNA) have not been well studied. Further, the existing methods have limitations in efficiency and yield. Therefore, we developed a highly efficient procedure for sequencing library preparation from ssDNA. Read More

RNA 2023 Aug 25. Epub 2023 Aug 25.

New England Biolabs, Inc.

The mammalian mRNA 5' cap structures play important roles in cellular processes such as nuclear export, efficient translation, and evading cellular innate immune surveillance and regulating 5'-mediated mRNA turnover. Hence, installation of the proper 5' cap is crucial in therapeutic applications of synthetic mRNA. The core 5' cap structure, Cap-0, is generated by three sequential enzymatic activities: RNA 5' triphosphatase, RNA guanylyltransferase, and cap N7-guanine methyltransferase. Read More

JMIR Res Protoc 2023 Aug 25;12:e46955. Epub 2023 Aug 25.

Disease Control and Prevention Center, Center Hospital of the National Center for Global Health and Medicine, Tokyo, Japan.

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. Read More

J Med Virol 2023 Aug;95(8):e29041

Shanghai Xuhui Central Hospital, Zhongshan-Xuhui Hospital, Shanghai Key Laboratory of Medical Epigenetics, Shanghai Stomatological Hospital, Institutes of Biomedical Sciences, Department of Chemistry, Fudan University, Shanghai, China.

The emerging outbreak of monkeypox is closely associated with the viral infection and spreading, threatening global public health. Virus-induced cell migration facilitates viral transmission. However, the mechanism underlying this type of cell migration remains unclear. Read More

Cancer Biol Med 2023 Aug 23. Epub 2023 Aug 23.

Department of Hematology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China.

Oncolytic virotherapy has emerged as a promising treatment for human cancers owing to an ability to elicit curative effects systemic administration. Tumor cells often create an unfavorable immunosuppressive microenvironment that degrade viral structures and impede viral replication; however, recent studies have established that viruses altered genetic modifications can serve as effective oncolytic agents to combat hostile tumor environments. Specifically, oncolytic vaccinia virus (OVV) has gained popularity owing to its safety, potential for systemic delivery, and large gene insertion capacity. Read More

Proc Natl Acad Sci U S A 2023 Aug 22;120(35):e2304242120. Epub 2023 Aug 22.

National Key Laboratory of Veterinary Public Health and Safety, Key Laboratory of Animal Epidemiology of the Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China.

Zoonotic poxviruses such as mpox virus (MPXV) continue to threaten public health safety since the eradication of smallpox. Vaccinia virus (VACV), the prototypic poxvirus used as the vaccine strain for smallpox eradication, is the best-characterized member of the poxvirus family. VACV encodes a serine protease inhibitor 1 (SPI-1) conserved in all orthopoxviruses, which has been recognized as a host range factor for modified VACV Ankara (MVA), an approved smallpox vaccine and a promising vaccine vector. Read More

Front Immunol 2023 4;14:1168784. Epub 2023 Aug 4.

Mayo Clinic Vaccine Research Group, Division of General Internal Medicine, Mayo Clinic, Rochester, MN, United States.

Background: In the vaccine era, individuals receive multiple vaccines in their lifetime. Host gene expression in response to antigenic stimulation is usually virus-specific; however, identifying shared pathways of host response across a wide spectrum of vaccine pathogens can shed light on the molecular mechanisms/components which can be targeted for the development of broad/universal therapeutics and vaccines.

Method: We isolated PBMCs, monocytes, B cells, and CD8 T cells from the peripheral blood of healthy donors, who received both seasonal influenza vaccine (within <1 year) and smallpox vaccine (within 1 - 4 years). Read More

Heliyon 2023 Aug 7;9(8):e18983. Epub 2023 Aug 7.

Department of Virology 1, National Institute of Infectious Diseases, Gakuen 4-7-1, Musashimurayama-shi, Tokyo, 208-0011, Japan.

Manipulating viral genomes is an essential technique in reverse genetics and recombinant vaccine development. A strategy for manipulating large viral genomes involves introducing their entire genome into bacterial artificial chromosomes and employing genetic tools. For sequence manipulation on bacterial artificial chromosomes (bacterial artificial chromosomes recombineering), a well-established method that relies on the strain GS1783, and the template plasmid, pEPKan-S, is often used. Read More

Microbiol Spectr 2023 Aug 18:e0139023. Epub 2023 Aug 18.

Division of Biology, Kansas State University , Manhattan, Kansas, USA.

In addition to the 3'-poly(A) tail, vaccinia virus mRNAs synthesized after viral DNA replication (post-replicative mRNAs) possess a 5'-poly(A) leader that confers a translational advantage in virally infected cells. These mRNAs are synthesized in viral factories, the cytoplasmic compartment where vaccinia virus DNA replication, mRNA synthesis, and translation occur. However, a previous study indicates that the poly(A)-binding protein (PABPC1)-which has a well-established role in RNA stability and translation-is absent in the viral factories. Read More