Giuseppe
Emeritus
Development of a highly efficacious vaccinia-based dual vaccine against smallpox and anthrax, two important bioterror entities (PNAS, abstract, edited)
[Source: PNAS, full text: <cite cite="http://www.pnas.org/content/107/42/18091.short?rss=1">Development of a highly efficacious vaccinia-based dual vaccine against smallpox and anthrax, two important bioterror entities ? PNAS</cite>. Abstract, edited.]
Development of a highly efficacious vaccinia-based dual vaccine against smallpox and anthrax, two important bioterror entities
1. Tod J. Merkel a,1, 2. Pin-Yu Perera b,1, 3. Vanessa K. Kelly a, 4. Anita Verma a, 5. Zara N. Llewellyn c, 6. Thomas A. Waldmann d,2, 7. Joseph D. Mosca e, and 8. Liyanage P. Perera d,2
Author Affiliations
1. aCenter for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892;
2. bVeterans Affairs Medical Center, Washington, DC 20422;
3. cSouthern Research Institute, Birmingham, AL 35255;
4. dMetabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892; and
5. eJDM Technologies, Ellicott City, MD 21042
1. Contributed by Thomas A. Waldmann, September 2, 2010 (sent for review May 26, 2010)
2. ↵1T.J.M. and P-Y.P. contributed equally to this work.
Abstract
Bioterrorism poses a daunting challenge to global security and public health in the 21st century. Variola major virus, the etiological agent of smallpox, and Bacillus anthracis, the bacterial pathogen responsible for anthrax, remain at the apex of potential pathogens that could be used in a bioterror attack to inflict mass casualties. Although licensed vaccines are available for both smallpox and anthrax, because of inadequacies associated with each of these vaccines, serious concerns remain as to the deployability of these vaccines, especially in the aftermath of a bioterror attack involving these pathogens. We have developed a single vaccine (Wyeth/IL-15/PA) using the licensed Wyeth smallpox vaccine strain that is efficacious against both smallpox and anthrax due to the integration of immune-enhancing cytokine IL-15 and the protective antigen (PA) of B. anthracis into the Wyeth vaccinia virus. Integration of IL-15 renders Wyeth vaccinia avirulent in immunodeficient mice and enhances anti-vaccinia immune responses. Wyeth/IL-15/PA conferred sterile protection against a lethal challenge of B. anthracis Ames strain spores in rabbits. A single dose of Wyeth/IL-15/PA protected 33% of the vaccinated A/J mice against a lethal spore challenge 72 h later whereas a single dose of licensed anthrax vaccine protected only 10%. Our dual vaccine Wyeth/IL-15/PA remedies the inadequacies associated with the licensed vaccines, and the inherent ability of Wyeth vaccinia virus to be lyophilized without loss of potency makes it cold-chain independent, thus simplifying the logistics of storage, stockpiling, and field delivery in the event of a bioterror attack involving smallpox or anthrax.
* biodefense
* IL-15
* bioterrorism
Footnotes
* 2 To whom correspondence may be addressed. E-mail: pereral@mail.nih.gov or tawald@helix.nih.gov.
* Author contributions: T.J.M., P.-Y.P., T.A.W., J.D.M., and L.P.P. designed research; T.J.M., P.-Y.P., V.K.K., A.V., Z.N.L., and L.P.P. performed research; Z.N.L. supervised rabbit immunization and challenge studies under contract; T.J.M., P.-Y.P., A.V., T.A.W., J.D.M., and L.P.P. analyzed data; and L.P.P. wrote the paper.
* The authors declare no conflict of interest.
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[Source: PNAS, full text: <cite cite="http://www.pnas.org/content/107/42/18091.short?rss=1">Development of a highly efficacious vaccinia-based dual vaccine against smallpox and anthrax, two important bioterror entities ? PNAS</cite>. Abstract, edited.]
Development of a highly efficacious vaccinia-based dual vaccine against smallpox and anthrax, two important bioterror entities
1. Tod J. Merkel a,1, 2. Pin-Yu Perera b,1, 3. Vanessa K. Kelly a, 4. Anita Verma a, 5. Zara N. Llewellyn c, 6. Thomas A. Waldmann d,2, 7. Joseph D. Mosca e, and 8. Liyanage P. Perera d,2
Author Affiliations
1. aCenter for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892;
2. bVeterans Affairs Medical Center, Washington, DC 20422;
3. cSouthern Research Institute, Birmingham, AL 35255;
4. dMetabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892; and
5. eJDM Technologies, Ellicott City, MD 21042
1. Contributed by Thomas A. Waldmann, September 2, 2010 (sent for review May 26, 2010)
2. ↵1T.J.M. and P-Y.P. contributed equally to this work.
Abstract
Bioterrorism poses a daunting challenge to global security and public health in the 21st century. Variola major virus, the etiological agent of smallpox, and Bacillus anthracis, the bacterial pathogen responsible for anthrax, remain at the apex of potential pathogens that could be used in a bioterror attack to inflict mass casualties. Although licensed vaccines are available for both smallpox and anthrax, because of inadequacies associated with each of these vaccines, serious concerns remain as to the deployability of these vaccines, especially in the aftermath of a bioterror attack involving these pathogens. We have developed a single vaccine (Wyeth/IL-15/PA) using the licensed Wyeth smallpox vaccine strain that is efficacious against both smallpox and anthrax due to the integration of immune-enhancing cytokine IL-15 and the protective antigen (PA) of B. anthracis into the Wyeth vaccinia virus. Integration of IL-15 renders Wyeth vaccinia avirulent in immunodeficient mice and enhances anti-vaccinia immune responses. Wyeth/IL-15/PA conferred sterile protection against a lethal challenge of B. anthracis Ames strain spores in rabbits. A single dose of Wyeth/IL-15/PA protected 33% of the vaccinated A/J mice against a lethal spore challenge 72 h later whereas a single dose of licensed anthrax vaccine protected only 10%. Our dual vaccine Wyeth/IL-15/PA remedies the inadequacies associated with the licensed vaccines, and the inherent ability of Wyeth vaccinia virus to be lyophilized without loss of potency makes it cold-chain independent, thus simplifying the logistics of storage, stockpiling, and field delivery in the event of a bioterror attack involving smallpox or anthrax.
* biodefense
* IL-15
* bioterrorism
Footnotes
* 2 To whom correspondence may be addressed. E-mail: pereral@mail.nih.gov or tawald@helix.nih.gov.
* Author contributions: T.J.M., P.-Y.P., T.A.W., J.D.M., and L.P.P. designed research; T.J.M., P.-Y.P., V.K.K., A.V., Z.N.L., and L.P.P. performed research; Z.N.L. supervised rabbit immunization and challenge studies under contract; T.J.M., P.-Y.P., A.V., T.A.W., J.D.M., and L.P.P. analyzed data; and L.P.P. wrote the paper.
* The authors declare no conflict of interest.
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