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Vaccines
Special Issues
Treatment of Orthopoxvirus Infections
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Treatment of Orthopoxvirus Infections

A special issue of Vaccines (ISSN 2076-393X). This special issue belongs to the section "Therapeutic Vaccines and Antibody Therapeutics".

Deadline for manuscript submissions: closed (15 February 2021) | Viewed by 13327

Special Issue Editor

Dr. Panayampalli Subbian Satheshkumar

E-Mail Website
Guest Editor
Poxvirus and Rabies Branch, Centers for Disease Control and Prevention, Atlanta, GA, USA
Interests: orthopoxvirus; vaccine; antiviral; proteomics; immune response; innate immunity
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Smallpox, caused by variola virus infection, was the most significant and devastating disease until its eradication. It still remains the only human disease completely eradicated through a successful vaccination campaign. As routine smallpox vaccination of the general public was discontinued, the majority of the current population are naive to orthopoxvirus infection. Currently, zoonotic transmission is the leading cause of orthopoxvirus infection, which varies based on the region. Human orthopoxvirus infections are predominantly caused by monkeypox virus in Africa, cowpoxvirus in Europe, vaccinia virus in South America, and buffalopoxvirus in Asia. While pre-exposure vaccination is hugely successful, it is less effective for post-exposure therapeutics. Due to the smallpox adverse effects caused by the replication of the competitive vaccinia virus in contraindicated individuals, a safer non-replicative vaccine was recently approved by the Food and Drug Administration (FDA). The efficacy of vaccines for post-exposure therapeutics needs to be further evaluated in animal models. TPOXX was approved for smallpox treatments by FDA recently. Still. there is a need for additional antivirals that target different steps in the orthopoxvirus lifecycle. Similarly, prophylactic treatment with antibodies against orthopoxviruses is needed. While polyclonal vaccinia immune globulin purified from immunized individuals is currently used, there is a need for alternate sources like monoclonal antibodies that can be produced continuously without variation. We hope this Special Issue will cover several of these important topics for treatment of orthopoxvirus infections.

Dr. Panayampalli Subbian Satheshkumar
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Vaccines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • orthopoxvirus
  • vaccine
  • antiviral
  • antibody prophylaxis
  • immune response
  • innate immunity
  • vaccine adverse effects
  • investigational therapy
  • animal models

Published Papers (3 papers)

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Research

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20 pages, 1074 KiB  
Article
Identification of Vaccinia Virus Inhibitors and Cellular Functions Necessary for Efficient Viral Replication by Screening Bioactives and FDA-Approved Drugs
by Chen Peng, Yanan Zhou, Shuai Cao, Anil Pant, Marlene L. Campos Guerrero, Peter McDonald, Anuradha Roy and Zhilong Yang
Vaccines 2020, 8(3), 401; https://doi.org/10.3390/vaccines8030401 - 21 Jul 2020
Cited by 10 | Viewed by 3795
Abstract
Four decades after the eradication of smallpox, poxviruses continue to threaten the health of humans and other animals. Vaccinia virus (VACV) was used as the vaccine that successfully eradicated smallpox and is a prototypic member of the poxvirus family. Many cellular pathways play [...] Read more.
Four decades after the eradication of smallpox, poxviruses continue to threaten the health of humans and other animals. Vaccinia virus (VACV) was used as the vaccine that successfully eradicated smallpox and is a prototypic member of the poxvirus family. Many cellular pathways play critical roles in productive poxvirus replication. These pathways provide opportunities to expand the arsenal of poxvirus antiviral development by targeting the cellular functions required for efficient poxvirus replication. In this study, we developed and optimized a secreted Gaussia luciferase-based, simplified assay procedure suitable for high throughput screening. Using this procedure, we screened a customized compound library that contained over 3200 bioactives and FDA (Food and Drug Administration)-approved chemicals, most having known cellular targets, for their inhibitory effects on VACV replication. We identified over 140 compounds that suppressed VACV replication. Many of these hits target cellular pathways previously reported to be required for efficient VACV replication, validating the effectiveness of our screening. Importantly, we also identified hits that target cellular functions with previously unknown roles in the VACV replication cycle. Among those in the latter category, we verified the antiviral role of several compounds targeting the janus kinase/signal transducer and activator of transcription-3 (JAK/STAT3) signaling pathway by showing that STAT3 inhibitors reduced VACV replication. Our findings identify pathways that are candidates for use in the prevention and treatment of poxvirus infections and additionally provide a foundation to investigate diverse cellular pathways for their roles in poxvirus replications. Full article
(This article belongs to the Special Issue Treatment of Orthopoxvirus Infections)
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22 pages, 3392 KiB  
Article
IMVAMUNE® and ACAM2000® Provide Different Protection against Disease When Administered Postexposure in an Intranasal Monkeypox Challenge Prairie Dog Model
by M. Shannon Keckler, Johanna S Salzer, Nishi Patel, Michael B Townsend, Yoshinori J Nakazawa, Jeffrey B Doty, Nadia F Gallardo-Romero, Panayampalli S Satheshkumar, Darin S Carroll, Kevin L Karem and Inger K Damon
Vaccines 2020, 8(3), 396; https://doi.org/10.3390/vaccines8030396 - 20 Jul 2020
Cited by 46 | Viewed by 4847
Abstract
The protection provided by smallpox vaccines when used after exposure to Orthopoxviruses is poorly understood. Postexposu re administration of 1st generation smallpox vaccines was effective during eradication. However, historical epidemiological reports and animal studies on postexposure vaccination are difficult to extrapolate to today’s [...] Read more.
The protection provided by smallpox vaccines when used after exposure to Orthopoxviruses is poorly understood. Postexposu re administration of 1st generation smallpox vaccines was effective during eradication. However, historical epidemiological reports and animal studies on postexposure vaccination are difficult to extrapolate to today’s populations, and 2nd and 3rd generation vaccines, developed after eradication, have not been widely tested in postexposure vaccination scenarios. In addition to concerns about preparedness for a potential malevolent reintroduction of variola virus, humans are becoming increasingly exposed to naturally occurring zoonotic orthopoxviruses and, following these exposures, disease severity is worse in individuals who never received smallpox vaccination. This study investigated whether postexposure vaccination of prairie dogs with 2nd and 3rd generation smallpox vaccines was protective against monkeypox disease in four exposure scenarios. We infected animals with monkeypox virus at doses of 104 pfu (2× LD50) or 106 pfu (170× LD50) and vaccinated the animals with IMVAMUNE® or ACAM2000® either 1 or 3 days after challenge. Our results indicated that postexposure vaccination protected the animals to some degree from the 2× LD50, but not the 170× LD5 challenge. In the 2× LD50 challenge, we also observed that administration of vaccine at 1 day was more effective than administration at 3 days postexposure for IMVAMUNE®, but ACAM2000® was similarly effective at either postexposure vaccination time-point. The effects of postexposure vaccination and correlations with survival of total and neutralizing antibody responses, protein targets, take formation, weight loss, rash burden, and viral DNA are also presented. Full article
(This article belongs to the Special Issue Treatment of Orthopoxvirus Infections)
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Review

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12 pages, 856 KiB  
Review
Corticosteroids Contribute to Serious Adverse Events Following Live Attenuated Varicella Vaccination and Live Attenuated Zoster Vaccination
by Nathan B. Price and Charles Grose
Vaccines 2021, 9(1), 23; https://doi.org/10.3390/vaccines9010023 - 06 Jan 2021
Cited by 11 | Viewed by 3719
Abstract
Corticosteroids, when given in high dosages, have long been recognized as a risk factor for severe infection with wild-type varicella-zoster virus in both children and adults. The goal of this review is to assess the degree to which both low-dosage and high-dosage corticosteroids [...] Read more.
Corticosteroids, when given in high dosages, have long been recognized as a risk factor for severe infection with wild-type varicella-zoster virus in both children and adults. The goal of this review is to assess the degree to which both low-dosage and high-dosage corticosteroids contribute to serious adverse events (SAEs) following live varicella vaccination and live zoster vaccination. To this end, we examined multiple published reports of SAEs following varicella vaccination (VarivaxTM) and zoster vaccination (ZostavaxTM). We observed that five of eight viral SAEs following varicella vaccination, including two deaths, occurred in children receiving corticosteroids, while one of three fatal viral SAEs following live zoster vaccination occurred in an adult being treated with low-dosage prednisone. The latter death after live zoster vaccination occurred in a 70 year-old man with rheumatoid arthritis, being treated with prednisone 10 mg daily. Thus, corticosteroids contributed to more severe infectious complications in subjects immunized with each of the two live virus vaccines. Further, when we surveyed the rheumatology literature as well as individual case reports, we documented examples where daily dosages of 7.5–20 mg prednisone were associated with increased rates of severe wild-type varicella-zoster virus infections in children and adults. Full article
(This article belongs to the Special Issue Treatment of Orthopoxvirus Infections)
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