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Xiangzhi Meng, Thomas Kaever, Bo Yan, Paula Traktman, Dirk M Zajonc, Bjoern Peters, Shane Crotty, Yan Xiang
Vaccinia virus (VACV) A14 is a major envelope protein and a dominant antibody target in the smallpox vaccine. However, the role of anti-A14 antibodies in immunity against orthopoxviruses is unclear. Here, we characterized 22 A14 monoclonal antibodies (mAb) from two mice immunized with VACV. Epitope mapping showed that 21 mAbs targeted the C-terminal hydrophilic region, while one mAb recognized the middle region predicted to be across the viral envelope from the C-terminus. However, none of the mAbs bound to virions in studies with electron microscopy...
March 17, 2018: Virology
Janelle Robertson, Jason Susong, Emily B Wong
In 2002, the United States implemented a new program for smallpox vaccinations among military personnel using a live vaccinia virus product. Approximately 2.4 million US military service members and health care workers have since been inoculated, with considerable numbers experiencing adverse reactions. Military dermatologists are at the forefront of describing and treating these reactions, from relatively benign generalized vaccinia (GV) and erythema multiforme (EM) to more severe progressive vaccinia (PV) and eczema vaccinatum (EV)...
February 2018: Cutis; Cutaneous Medicine for the Practitioner
C Raina MacIntyre, Valentina Costantino, Xin Chen, Eva Segelov, Abrar Ahmad Chughtai, Anthony Kelleher, Mohana Kunasekaran, John Michael Lane
We built a SEIR (susceptible, exposed, infected, recovered) model of smallpox transmission for New York, New York, USA, and Sydney, New South Wales, Australia, that accounted for age-specific population immunosuppression and residual vaccine immunity and conducted sensitivity analyses to estimate the effect these parameters might have on smallpox reemergence. At least 19% of New York's and 17% of Sydney's population are immunosuppressed. The highest smallpox infection rates were in persons 0-19 years of age, but the highest death rates were in those >45 years of age...
April 2018: Emerging Infectious Diseases
Todd R Kramer
This case report examines a vesiculopustular reaction which occurred in a young Marine 9 d after receiving the smallpox vaccination. Review of the CDC guidelines, ACAM2000 package insert, and literature surrounding the smallpox vaccine reveals several well-established adverse cutaneous reactions associated with vaccination. These dermatologic reactions are typically mild and self-limited, but do have the potential to be life threatening - especially in those with immunocompromise. Unfortunately, the correct diagnosis can often be difficult to make, as many of these rashes share similar characteristics...
March 13, 2018: Military Medicine
V Puro, F M Fusco, C Castilletti, F Carletti, F Colavita, C Agrati, A Di Caro, M R Capobianchi, G Ippolito
Orthopoxviruses spill over from animal reservoirs to accidental hosts, sometimes causing human infections. We describe the surveillance and infection control measures undertaken during an outbreak due to an Orthopoxvirus occurred in January 2015 in a colony of Macaca tonkeana in the province of Rieti, Latio, Italy, which caused a human asymptomatic infection. According to the epidemiological investigation, the human transmission occurred after an unprotected exposure. The contacts among wild, captive and domestic animals and humans, together with decreased immunity against Orthopoxviruses in the community, may put animal handlers at risk of infection, especially after the cessation of smallpox vaccination...
March 7, 2018: Zoonoses and Public Health
Melanie Laura Duncan, Jacquelyn Horsington, Preethi Eldi, Zahrah Al Rumaih, Gunasegaran Karupiah, Timothy P Newsome
Ectromelia virus (ECTV) is an orthopoxvirus and the causative agent of mousepox. Like other poxviruses such as variola virus (agent of smallpox), monkeypox virus and vaccinia virus (the live vaccine for smallpox), ECTV promotes actin-nucleation at the surface of infected cells during virus release. Homologs of the viral protein A36 mediate this function through phosphorylation of one or two tyrosine residues that ultimately recruit the cellular Arp2/3 actin-nucleating complex. A36 also functions in the intracellular trafficking of virus mediated by kinesin-1...
March 5, 2018: Viruses
Jonas D Albarnaz, Alice A Torres, Geoffrey L Smith
The increasing frequency of monkeypox virus infections, new outbreaks of other zoonotic orthopoxviruses and concern about the re-emergence of smallpox have prompted research into developing antiviral drugs and better vaccines against these viruses. This article considers the genetic engineering of vaccinia virus (VACV) to enhance vaccine immunogenicity and safety. The virulence, immunogenicity and protective efficacy of VACV strains engineered to lack specific immunomodulatory or host range proteins are described...
February 28, 2018: Viruses
Iliana Georgana, Rebecca P Sumner, Greg J Towers, Carlos Maluquer de Motes
Cytosolic recognition of DNA has emerged as a critical cellular mechanism of host immune activation upon pathogen invasion. The central cytosolic DNA sensor cGAS activates STING, which is phosphorylated, dimerises and translocates from the ER to a perinuclear region to mediate IRF-3 activation. Poxviruses are dsDNA viruses replicating in the cytosol and hence likely to trigger cytosolic DNA sensing. Here we investigated the activation of innate immune signalling by 4 different strains of the prototypic poxvirus vaccinia virus (VACV) in a cell line proficient in DNA sensing...
February 28, 2018: Journal of Virology
Tomoki Yoshikawa, Hikaru Fujii, Akiko Okutani, Miho Shibamura, Natsumi Omura, Kazutaka Egawa, Hirofumi Kato, Takuya Inagaki, Shizuko Harada, Souichi Yamada, Shigeru Morikawa, Masayuki Saijo
LC16m8 (m8), a highly attenuated vaccinia virus (VAC) strain, was developed as a smallpox vaccine, and its safety and immunogenicity have been confirmed. Here, we aimed to develop a system that recovers infectious m8 from a bacterial artificial chromosome (BAC) that retains the full-length viral genomic DNA (m8-BAC system). The infectious virus was successfully recovered from a VAC-BAC plasmid, named pLC16m8-BAC. Furthermore, the bacterial replicon-free virus was generated by intramolecular homologous recombination and was successfully recovered from a modified VAC-BAC plasmid, named pLC16m8...
2018: PloS One
Ela Alcántara-Flores, Alicia E Brechú-Franco, Angel Villegas-Monter, Guillermo Laguna-Hernández, Armando Gómez-Campos
Phyllonoma laticuspis leaves are used in Carrizal de Bravo, Guerrero, Mexico, to heal skin lesions such as injuries and smallpox sequelae and to treat diabetes mellitus type 2, and organic extracts of these leaves have been reported to exert antibacterial effects. High demand of P. laticuspis as a medicinal plant has decreased its natural populations, and propagation of the species has not yet been reported. Therefore, the purpose of this study was to assess the vegetative propagation of the species through cutting and air layering, as well as its sexual propagation in a preserved population...
March 2017: Revista de Biología Tropical
Jennifer Kuntz, Bradley Crane, Sheila Weinmann, Allison L Naleway
Reports of myocarditis and pericarditis following smallpox vaccination in adults suggested a need to assess inflammatory cardiac disease risk among adults who receive live viral vaccinations. From 1996 through 2007, among 416,629 vaccinated adults in the Vaccine Safety Datalink, we identified one probable pericarditis case and no cases of myocarditis in the 42 days following a live viral vaccination. Our self-controlled risk interval analysis found that, based on one case identified during the risk interval and 10 cases during the control interval, there is no increased risk of myopericarditis in the 42 days following vaccination (IRR, 0...
March 14, 2018: Vaccine
Gianguglielmo Zehender, Alessia Lai, Carla Veo, Annalisa Bergna, Massimo Ciccozzi, Massimo Galli
Variola virus (VARV), the causative agent of smallpox, is an exclusively human virus belonging to the genus Orthopoxvirus, which includes many other viral species covering a wide range of mammal hosts, such as vaccinia, cowpox, camelpox, taterapox, ectromelia and monkeypox virus. The tempo and mode of evolution of Orthopoxviruses were reconstructed using a Bayesian phylodynamic framework by analysing 80 hemagglutinin sequences retrieved from public databases. Bayesian phylogeography was used to estimate their putative ancestral hosts...
February 15, 2018: Journal of Medical Virology
Valentina Costantino, Mohana P Kunasekaran, Abrar A Chughtai, Chandini R MacIntyre
Background: Globally eradicated in 1980, smallpox is listed as a category A bioterrorism agent. If smallpox were to re-emerge, it may be due to an act of bioterrorism or a laboratory accident, and the impact is likely to be severe. Preparedness against smallpox is subject to more uncertainty than other infectious diseases because it is eradicated, there is uncertainty about population immunity, and the current global health workforce has no practical experience or living memory of smallpox...
February 7, 2018: Military Medicine
Julie R Whittington, Nanette L Rollene, Richard S Gist
Introduction: Smallpox, or vaccinia, has been eradicated worldwide as a disease; however, it may be weaponized and is thus a required immunization when military members deploy to certain parts of the world. Materials and Methods: We report two unusual cases of genital autoinoculation following smallpox vaccination. Results: Both patients' lesions resolved without sequelae within 20 d. Conclusions: We advocate for thorough education on this potential vaccination adverse event...
February 5, 2018: Military Medicine
Madeline S Tiee, Ryan J Harrigan, Henri A Thomassen, Thomas B Smith
Infectious diseases that originate from multiple wildlife hosts can be complex and problematic to manage. A full understanding is further limited by large temporal and spatial gaps in sampling. However, these limitations can be overcome, in part, by using historical samples, such as those derived from museum collections. Here, we screened over 1000 museum specimens collected over the past 120 years to examine the historical distribution and prevalence of monkeypox virus (MPXV) in five species of African rope squirrel ( Funisciurus sp...
January 2018: Royal Society Open Science
Emma Rey-Jurado, Felipe Tapia, Natalia Muñoz-Durango, Margarita K Lay, Leandro J Carreño, Claudia A Riedel, Susan M Bueno, Yvonne Genzel, Alexis M Kalergis
Vaccines have significantly reduced the detrimental effects of numerous human infectious diseases worldwide, helped to reduce drastically child mortality rates and even achieved eradication of major pathogens, such as smallpox. These achievements have been possible due to a dedicated effort for vaccine research and development, as well as an effective transfer of these vaccines to public health care systems globally. Either public or private institutions have committed to developing and manufacturing vaccines for local or international population supply...
2018: Frontiers in Immunology
Antonia Kotsiou, Vasiliki Michalaki, Helen N Anagnostopoulou
In the recent Greek ages the most devastating epidemics were plague, smallpox, leprosy and cholera. In 1816 plague struck the Ionian and Aegean Islands, mainland Greece, Constantinople and Smyrna. The Venetians ruling the Ionian Islands effectively combated plague in contrast to the Ottomans ruling all other regions. In 1922, plague appeared in Patras refugees who were expelled by the Turks from Smyrna and Asia Minor. Inoculation against smallpox was first performed in Thessaly by the Greek women, and the Greek doctors Emmanouel Timonis (1713, Oxford) and Jakovos Pylarinos (1715, Venice) made relevant scientific publications...
December 2017: Acta Medico-historica Adriatica: AMHA
Sharon Melamed, Tomer Israely, Nir Paran
Declaration of smallpox eradication by the WHO in 1980 led to discontinuation of the worldwide vaccination campaign. The increasing percentage of unvaccinated individuals, the existence of its causative infectious agent variola virus (VARV), and the recent synthetic achievements increase the threat of intentional or accidental release and reemergence of smallpox. Control of smallpox would require an emergency vaccination campaign, as no other protective measure has been approved to achieve eradication and ensure worldwide protection...
January 29, 2018: Vaccines
Ryan S Noyce, Seth Lederman, David H Evans
Edward Jenner and his contemporaries believed that his variolae vaccinae originated in horses and molecular analyses show that modern vaccinia virus (VACV) strains share common ancestry with horsepox virus (HPXV). Given concerns relating to the toxicity of modern VACV vaccines, we asked whether an HPXV-based vaccine might provide a superior alternative. Since HPXV may be extinct and the only specimen of HPXV that has been identified is unavailable for investigation, we explored whether HPXV could be obtained by large-scale gene synthesis...
2018: PloS One
Nicholas G Reich, Justin Lessler, Jay K Varma, Neil M Vora
During outbreaks of deadly emerging pathogens (e.g., Ebola, MERS-CoV) and bioterror threats (e.g., smallpox), actively monitoring potentially infected individuals aims to limit disease transmission and morbidity. Guidance issued by CDC on active monitoring was a cornerstone of its response to the West Africa Ebola outbreak. There are limited data on how to balance the costs and performance of this important public health activity. We present a framework that estimates the risks and costs of specific durations of active monitoring for pathogens of significant public health concern...
January 18, 2018: Scientific Reports
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