The Experts below are selected from a list of 285 Experts worldwide ranked by ideXlab platform
Scott Foster - One of the best experts on this subject based on the ideXlab platform.
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The efficacy and pharmacokinetics of brincidofovir for the treatment of lethal rabbitpox virus infection: a model of Smallpox disease.
Antiviral Research, 2015Co-Authors: Lawrence C. Trost, Laurie Keilholz, Jody M. Khouri, Michelle L. Rose, James Long, Stephen J. Godin, Scott FosterAbstract:Brincidofovir (BCV) has broad-spectrum in vitro activity against dsDNA viruses, including Smallpox, and is being developed as a treatment for Smallpox as well as infections caused by other dsDNA viruses. BCV has previously been shown to be active in multiple animal models of Smallpox. Here we present the results of a randomized, blinded, placebo-controlled study of the efficacy and pharmacokinetics of a novel, "humanized" regimen of BCV for treatment of New Zealand White rabbits infected with a highly lethal inoculum of rabbitpox virus, a well characterized model of Smallpox. Compared with placebo, a dose-dependent increase in survival was observed in all BCV-treatment groups. Concentrations of cidofovir diphosphate (CDV-PP), the active antiviral, in rabbit peripheral blood mononuclear cells (PBMCs) were determined for comparison to those produced in humans at the dose proposed for treatment of Smallpox. CDV-PP exposure in PBMCs from rabbits given BCV scaled to human exposures at the dose proposed for treatment of Smallpox, which is also currently under evaluation for other indications. The results of this study demonstrate the activity of BCV in the rabbitpox model of Smallpox and the feasibility of scaling doses efficacious in the model to a proposed human dose and regimen for treatment of Smallpox.
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Efficacy of CMX001 as a prophylactic and presymptomatic antiviral agent in New Zealand white rabbits infected with rabbitpox virus, a model for orthopoxvirus infections of humans.
Viruses, 2011Co-Authors: Amanda D. Rice, Scott Foster, Mathew M. Adams, Bernhard Lampert, Randall Lanier, Alice Robertson, George R. Painter, Richard W. MoyerAbstract:CMX001, a lipophilic nucleotide analog formed by covalently linking 3-(hexdecyloxy)propan-1-ol to cidofovir (CDV), is being developed as a treatment for Smallpox. CMX001 has dramatically increased potency versus CDV against all dsDNA viruses and, in contrast to CDV, is orally available and has shown no evidence of nephrotoxicity in healthy volunteers or severely ill transplant patients to date. Although Smallpox has been eliminated from the environment, treatments are urgently being sought due to the risk of Smallpox being used as a bioterrorism agent and for monkeypox virus, a zoonotic disease of Africa, and adverse reactions to Smallpox virus vaccinations. In the absence of human cases of Smallpox, new treatments must be tested for efficacy in animal models. Here we first review and discuss the rabbitpox virus (RPV) infection of New Zealand White rabbits as a model for Smallpox to test the efficacy of CMX001 as a prophylactic and early disease antiviral. Our results should also be applicable to monkeypox virus infections and for treatment of adverse reactions to Smallpox vaccination.
Kathleen J. Weldon - One of the best experts on this subject based on the ideXlab platform.
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The public and the Smallpox threat.
The New England journal of medicine, 2002Co-Authors: Robert J. Blendon, Catherine M. Desroches, John M. Benson, Melissa J. Herrmann, Kalahn Taylor-clark, Kathleen J. WeldonAbstract:Background The potential for a bioterrorist attack involving Smallpox has led to a debate about what national precautions should be taken. What is unclear is the public's knowledge of Smallpox and views about precautions. Methods We conducted a national survey of 1006 adults selected by means of random-digit dialing. Respondents were asked about their knowledge of and beliefs about the Smallpox virus and the vaccine, their possible reactions to a bioterrorist attack involving Smallpox, and a number of proposed state emergency powers. Results The majority of the respondents have a number of beliefs about Smallpox and Smallpox vaccination that are false. The majority believe that there is an effective treatment for Smallpox, that there have been cases of Smallpox in the past five years, and that there is not enough Smallpox vaccine to vaccinate everyone in the United States. Thirty percent believe that vaccination earlier in their lives would protect them from the disease. The majority of respondents said t...
Robert J. Blendon - One of the best experts on this subject based on the ideXlab platform.
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The public and the Smallpox threat.
The New England journal of medicine, 2002Co-Authors: Robert J. Blendon, Catherine M. Desroches, John M. Benson, Melissa J. Herrmann, Kalahn Taylor-clark, Kathleen J. WeldonAbstract:Background The potential for a bioterrorist attack involving Smallpox has led to a debate about what national precautions should be taken. What is unclear is the public's knowledge of Smallpox and views about precautions. Methods We conducted a national survey of 1006 adults selected by means of random-digit dialing. Respondents were asked about their knowledge of and beliefs about the Smallpox virus and the vaccine, their possible reactions to a bioterrorist attack involving Smallpox, and a number of proposed state emergency powers. Results The majority of the respondents have a number of beliefs about Smallpox and Smallpox vaccination that are false. The majority believe that there is an effective treatment for Smallpox, that there have been cases of Smallpox in the past five years, and that there is not enough Smallpox vaccine to vaccinate everyone in the United States. Thirty percent believe that vaccination earlier in their lives would protect them from the disease. The majority of respondents said t...
Mark K Slifka - One of the best experts on this subject based on the ideXlab platform.
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antiviral immunity following Smallpox virus infection a case control study
Journal of Virology, 2010Co-Authors: Erika Hammarlund, Matthew W Lewis, Jon M Hanifin, Motomi Mori, Caroline Koudelka, Mark K SlifkaAbstract:Outbreaks of Smallpox (i.e., caused by variola virus) resulted in up to 30% mortality, but those who survived Smallpox infection were regarded as immune for life. Early studies described the levels of neutralizing antibodies induced after infection, but Smallpox was eradicated before contemporary methods for quantifying T-cell memory were developed. To better understand the levels and duration of immunity after Smallpox infection, we performed a case-control study comparing antiviral CD4 and CD8 T-cell responses and neutralizing antibody levels of 24 Smallpox survivors with the antiviral immunity observed in 60 Smallpoxvaccinated (i.e., vaccinia virus-immune) control subjects. We found that the duration of immunity following Smallpox infection was remarkably similar to that observed after Smallpox vaccination, with antiviral T-cell responses that declined slowly over time and antiviral antibody responses that remained stable for decades after recovery from infection. These results indicate that severe, potentially life-threatening disease is not required for the development of sustainable long-term immunity. This study shows that the levels of immunity induced following Smallpox vaccination are comparable in magnitude to that achieved through natural variola virus infection, and this may explain the notable success of vaccination in eradicating Smallpox, one of the world’s most lethal diseases.
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The Future of Smallpox Vaccination: is MVA the key?
Medical Immunology, 2005Co-Authors: Mark K SlifkaAbstract:Eradication of the Smallpox virus through extensive global vaccination efforts has resulted in one of the most important breakthroughs in medical history, saving countless lives from the severe morbidity and mortality that is associated with this disease. Although Smallpox is now extinct in nature, laboratory stocks of this virus still remain and the subject of Smallpox vaccination has gained renewed attention due to the potential risk that Smallpox may be used as a biological weapon by terrorists or rogue states. Despite having the longest history of any modern vaccine, there is still much to be learned about Smallpox vaccination and the correlates of protection remain to be formally defined. This Commentary will discuss the strengths and weaknesses of traditional Smallpox vaccination in comparison with immunization using modified vaccinia virus Ankura (MVA), a non-replicating virus with a strong safety record but weakened immunogenicity.
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Smallpox: the basics.
Dermatologic clinics, 2004Co-Authors: Mark K Slifka, Jon M HanifinAbstract:Variola major is the causative agent of Smallpox, a severe disease that was arguably one of the most serious human pathogens in recorded history. Humans are the only known reservoir of variola major; no known animal or insect reservoirs have been identified. Thus, after eradication of Smallpox through a global immunization effort, this incredibly lethal scourge was eliminated from all corners of the globe. Despite the total eradication of naturally occurring Smallpox, there are still stockpiles of Smallpox virus maintained in the United States and the former Soviet Union. Unfortunately, it is impossible to know if all Smallpox stocks have been accounted for or whether unknown or unreported stocks of Smallpox may still exist. In the age of genetic engineering, these viruses could theoretically be modified to increase their virulence to the levels associated with Smallpox itself.
Richard W. Moyer - One of the best experts on this subject based on the ideXlab platform.
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Efficacy of CMX001 as a prophylactic and presymptomatic antiviral agent in New Zealand white rabbits infected with rabbitpox virus, a model for orthopoxvirus infections of humans.
Viruses, 2011Co-Authors: Amanda D. Rice, Scott Foster, Mathew M. Adams, Bernhard Lampert, Randall Lanier, Alice Robertson, George R. Painter, Richard W. MoyerAbstract:CMX001, a lipophilic nucleotide analog formed by covalently linking 3-(hexdecyloxy)propan-1-ol to cidofovir (CDV), is being developed as a treatment for Smallpox. CMX001 has dramatically increased potency versus CDV against all dsDNA viruses and, in contrast to CDV, is orally available and has shown no evidence of nephrotoxicity in healthy volunteers or severely ill transplant patients to date. Although Smallpox has been eliminated from the environment, treatments are urgently being sought due to the risk of Smallpox being used as a bioterrorism agent and for monkeypox virus, a zoonotic disease of Africa, and adverse reactions to Smallpox virus vaccinations. In the absence of human cases of Smallpox, new treatments must be tested for efficacy in animal models. Here we first review and discuss the rabbitpox virus (RPV) infection of New Zealand White rabbits as a model for Smallpox to test the efficacy of CMX001 as a prophylactic and early disease antiviral. Our results should also be applicable to monkeypox virus infections and for treatment of adverse reactions to Smallpox vaccination.
