Analyze Diet
Infection and immunity2003; 71(3); 1491-1496; doi: 10.1128/IAI.71.3.1491-1496.2003

Venezuelan equine encephalitis virus-vectored vaccines protect mice against anthrax spore challenge.

Abstract: Anthrax, a disease usually associated with herbivores, is caused by the bacterium Bacillus anthracis. The current vaccine licensed for human use requires a six-dose primary series and yearly boosters and causes reactogenicity in up to 30% of vaccine recipients. A minimally reactogenic vaccine requiring fewer inoculations is warranted. Venezuelan equine encephalitis (VEE) virus has been configured for use as a vaccine vector for a wide variety of immunogens. The VEE vaccine vector is composed of a self-replicating RNA (replicon) containing all of the VEE virus nonstructural genes and a multiple-cloning site in place of the VEE structural genes. Four different anthrax vaccines were constructed by cloning the protective antigen (PA) gene from B. anthracis into the VEE vaccine vector. The anthrax vaccines were produced by assembling the vectors into propagation-deficient VEE replicon particles in vitro. A/J mice inoculated subcutaneously with three doses of the mature 83-kDa PA vaccine were completely protected from challenge with the Sterne strain of B. anthracis. Similar results were obtained with vaccines composed of the PA gene fused to either the B. anthracis secretory sequence or to a tissue plasminogen activator secretory sequence in three additional mouse strains. Mice were unprotected from challenge after inoculation with the carboxy-terminal 63-kDa PA vaccine. These results suggest that these VEE-vectored vaccines may be suitable as candidate vaccines against anthrax.
Publication Date: 2003-02-22 PubMed ID: 12595467PubMed Central: PMC148867DOI: 10.1128/IAI.71.3.1491-1496.2003Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
  • Journal Article

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research paper discusses the development and testing of anthrax vaccines using genetically modified Venezuelan equine encephalitis (VEE) virus as carriers. The study shows promising results with the anthrax vaccines, offering full protection against the disease in various mouse strains.

Objective of the Research

  • The primary aim of this study was to develop a new anthrax vaccine using Venezuelan equine encephalitis (VEE) virus as a vector. This was encouraged by the need to create a minimally reactogenic vaccine that requires fewer inoculations than the currently used human anthrax vaccine.

About Venezuelan Equine Encephalitis Virus

  • VEE virus has been adapted for use as a vaccine carrier for various immunogens. This viral vector features a self-replicating RNA replicon holding all of VEE virus’s nonstructural genes and a multiple-cloning site replacing the structural genes of the VEE virus.

Development of Anthrax Vaccines

  • Four different anthrax vaccines were created by introducing a protective antigen (PA) gene from Bacillus anthracis, the bacterium that causes anthrax, into the VEE vaccine vector.
  • The anthrax vaccines were produced by assembling the modified vectors into propagation-deficient VEE replicon particles in vitro.

Testing of the Vaccines

  • Mouse model was used to test the effectiveness of the anthrax vaccines. A/J mouse strain inoculated subcutaneously with three doses of mature 83-kDa PA vaccine displayed complete protection from anthrax using the Sterne strain of Bacillus anthracis.
  • Similar protection results were noted with vaccines utilizing PA gene fused to either a Bacillus anthracis secretory sequence or a tissue plasminogen activator secretory sequence in three additional mouse strains.
  • However, mice remained unprotected from anthrax after inoculation with the carboxy-terminal 63-kDa PA vaccine.

Implications of the Research

  • Given the successful results of the study, these VEE-vectored vaccines indicate promise as potential vaccines against anthrax, especially considering the limitations of the current vaccine used on humans.

Cite This Article

APA
Lee JS, Hadjipanayis AG, Welkos SL. (2003). Venezuelan equine encephalitis virus-vectored vaccines protect mice against anthrax spore challenge. Infect Immun, 71(3), 1491-1496. https://doi.org/10.1128/IAI.71.3.1491-1496.2003

Publication

ISSN: 0019-9567
NlmUniqueID: 0246127
Country: United States
Language: English
Volume: 71
Issue: 3
Pages: 1491-1496

Researcher Affiliations

Lee, John S
  • Virology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, Maryland 21702, USA. John.Lee@det.amedd.army.mil
Hadjipanayis, Angela G
    Welkos, Susan L

      MeSH Terms

      • Animals
      • Anthrax Vaccines / immunology
      • Antibodies, Bacterial / biosynthesis
      • Antigens, Bacterial
      • Bacillus anthracis / pathogenicity
      • Bacterial Toxins / genetics
      • Bacterial Toxins / immunology
      • Encephalitis Virus, Venezuelan Equine / genetics
      • Genetic Vectors
      • Mice
      • Species Specificity
      • Spores, Bacterial / pathogenicity
      • Vaccination
      • Vaccines, Synthetic / immunology

      References

      This article includes 16 references
      1. Flick-Smith HC, Walker NJ, Gibson P, Bullifent H, Hayward S, Miller J, Titball RW, Williamson ED. A recombinant carboxy-terminal domain of the protective antigen of Bacillus anthracis protects mice against anthrax infection.. Infect. Immun. 70:1653-1656.
        pmc: PMC127760pubmed: 11854261
      2. Hevey M, Negley D, Pushko P, Smith J, Schmaljohn A. Marburg virus vaccines based upon alphavirus replicons protect guinea pigs and nonhuman primates.. Virology 251:28-37.
        pubmed: 9813200
      3. Iacono-Connors LC, Welkos SL, Ivins BE, Dalrymple JM. Protection against anthrax with recombinant virus-expressed protective antigen in experimental animals.. Infect. Immun. 59:1961-1965.
        pmc: PMC257950pubmed: 1903769
      4. Inglesby TV, O'Toole T, Henderson DA, Bartlett JG, Ascher MS, Eitzen E, Friedlander A, Gerberding J, Hauer J, Hughes J, McDade J, Osterholm MT, Parker G, Perl TM, Russell PK, Tonat K. Anthrax as a biological weapon, 2002: updated recommendations for management.. JAMA 287:2236-2252.
        pubmed: 11980524
      5. Ivins B, Welkos SL. Recent advances in the development of an improved, human anthrax vaccine.. Eur. J. Epidemiol. 4:12-19.
        pubmed: 3128450
      6. Lee JS, Dyas BK, Nystrom SS, Lind CM, Smith JF, Ulrich RG. Immune protection against staphylococcal enterotoxin-induced toxic shock by vaccination with a Venezuelan equine encephalitis virus replicon.. J. Infect. Dis. 185:1192-1196.
        pubmed: 11930333
      7. Lee JS, Pushko P, Parker MD, Dertzbaugh MT, Smith LA, Smith JF. Candidate vaccine against botulinum neurotoxin serotype A derived from a Venezuelan equine encephalitis virus vector system.. Infect. Immun. 69:5709-5715.
        pmc: PMC98687pubmed: 11500447
      8. Petosa C, Collier RJ, Klimpel KR, Leppla SH, Liddington RC. Crystal structure of the anthrax toxin protective antigen.. Nature 385:833-838.
        pubmed: 9039918
      9. Pitt MLM, Little S, Ivins B, Fellows P, Barth J, Hewetson J, Gibbs P, Dertzbaugh M, Friedlander A. In vitro correlate of immunity in a rabbit model of inhalation anthrax.. Vaccine 19:4768-4773.
        pubmed: 11535328
      10. Pushko P, Parker M, Geisbert J, Negley D, Schmaljohn A, Jahrling P, Smith J. Venezuelan equine encephalitis virus replicon vector: immunogenicity studies with ebola NP and GP genes in guinea pigs.. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y..
      11. Pushko P, Parker M, Ludwig GV, Davis NL, Johnston RE, Smith JF. Replicon-helper systems from attenuated Venezuelan equine encephalitis virus: expression of heterologous genes in vitro and immunization against heterologous pathogens in vivo.. Virology 239:389-401.
        pubmed: 9434729
      12. Singh Y, Ivins B, Leppla SH. Study of immunization against anthrax with the purified recombinant protective antigen of Bacillus anthracis.. Infect. Immun. 66:3447-3448.
        pmc: PMC108368pubmed: 9632621
      13. Strauss JH, Strauss EG. The alphaviruses: gene expression, replication, and evolution.. Microbiol. Rev. 58:491-562.
        pmc: PMC372977pubmed: 7968923
      14. Welkos SL, Friedlander A. Comparative safety and efficacy against Bacillus anthracis of protective antigen and live vaccines in mice.. Microb. Pathog. 5:127-139.
        pubmed: 3148815
      15. Welkos SL, Friedlander AM. Pathogenesis and genetic control of resistance to the Sterne strain of Bacillus anthracis.. Microb. Pathog. 4:53-69.
        pubmed: 3143893
      16. Welkos SL, Vietri NJ, Gibbs PH. Non-toxigenic derivatives of the Ames strain of Bacillus anthracis are fully virulent for mice: role of plasmid pX02 and chromosome in strain-dependent virulence.. Microb. Pathog. 14:381-388.
        pubmed: 8366815

      Citations

      This article has been cited 16 times.
      1. Reed DS, Glass PJ, Bakken RR, Barth JF, Lind CM, da Silva L, Hart MK, Rayner J, Alterson K, Custer M, Dudek J, Owens G, Kamrud KI, Parker MD, Smith J. Combined alphavirus replicon particle vaccine induces durable and cross-protective immune responses against equine encephalitis viruses. J Virol 2014 Oct;88(20):12077-86.
        doi: 10.1128/JVI.01406-14pubmed: 25122801google scholar: lookup
      2. Khalil SM, Tonkin DR, Mattocks MD, Snead AT, Johnston RE, White LJ. A tetravalent alphavirus-vector based dengue vaccine provides effective immunity in an early life mouse model. Vaccine 2014 Jul 7;32(32):4068-74.
        doi: 10.1016/j.vaccine.2014.05.053pubmed: 24882043google scholar: lookup
      3. Merkel TJ, Perera PY, Lee GM, Verma A, Hiroi T, Yokote H, Waldmann TA, Perera LP. Protective-antigen (PA) based anthrax vaccines confer protection against inhalation anthrax by precluding the establishment of a systemic infection. Hum Vaccin Immunother 2013 Sep;9(9):1841-8.
        doi: 10.4161/hv.25337pubmed: 23787486google scholar: lookup
      4. Diaz-San Segundo F, Dias CC, Moraes MP, Weiss M, Perez-Martin E, Owens G, Custer M, Kamrud K, de los Santos T, Grubman MJ. Venezuelan equine encephalitis replicon particles can induce rapid protection against foot-and-mouth disease virus. J Virol 2013 May;87(10):5447-60.
        doi: 10.1128/JVI.03462-12pubmed: 23468490google scholar: lookup
      5. Dahiya SS, Saini M, Kumar P, Gupta PK. Immunogenicity of a DNA-launched replicon-based canine parvovirus DNA vaccine expressing VP2 antigen in dogs. Res Vet Sci 2012 Oct;93(2):1089-97.
        doi: 10.1016/j.rvsc.2012.01.017pubmed: 22349592google scholar: lookup
      6. Merkel TJ, Perera PY, Kelly VK, Verma A, Llewellyn ZN, Waldmann TA, Mosca JD, Perera LP. Development of a highly efficacious vaccinia-based dual vaccine against smallpox and anthrax, two important bioterror entities. Proc Natl Acad Sci U S A 2010 Oct 19;107(42):18091-6.
        doi: 10.1073/pnas.1013083107pubmed: 20921397google scholar: lookup
      7. Thomas JM, Moen ST, Gnade BT, Vargas-Inchaustegui DA, Foltz SM, Suarez G, Heidner HW, König R, Chopra AK, Peterson JW. Recombinant Sindbis virus vectors designed to express protective antigen of Bacillus anthracis protect animals from anthrax and display synergy with ciprofloxacin. Clin Vaccine Immunol 2009 Nov;16(11):1696-9.
        doi: 10.1128/CVI.00173-09pubmed: 19759250google scholar: lookup
      8. Cybulski RJ Jr, Sanz P, O'Brien AD. Anthrax vaccination strategies. Mol Aspects Med 2009 Dec;30(6):490-502.
        doi: 10.1016/j.mam.2009.08.006pubmed: 19729034google scholar: lookup
      9. Nishimoto KP, Laust AK, Nelson EL. A human dendritic cell subset receptive to the Venezuelan equine encephalitis virus-derived replicon particle constitutively expresses IL-32. J Immunol 2008 Sep 15;181(6):4010-8.
        doi: 10.4049/jimmunol.181.6.4010pubmed: 18768856google scholar: lookup
      10. Kamrud KI, Alterson KD, Andrews C, Copp LO, Lewis WC, Hubby B, Patel D, Rayner JO, Talarico T, Smith JF. Analysis of Venezuelan equine encephalitis replicon particles packaged in different coats. PLoS One 2008 Jul 16;3(7):e2709.
        doi: 10.1371/journal.pone.0002709pubmed: 18628938google scholar: lookup
      11. Liu YT, Lin SB, Huang CP, Huang CM. A novel immunogenic spore coat-associated protein in Bacillus anthracis: characterization via proteomics approaches and a vector-based vaccine system. Protein Expr Purif 2008 Jan;57(1):72-80.
        doi: 10.1016/j.pep.2007.08.016pubmed: 18029197google scholar: lookup
      12. Kamrud KI, Custer M, Dudek JM, Owens G, Alterson KD, Lee JS, Groebner JL, Smith JF. Alphavirus replicon approach to promoterless analysis of IRES elements. Virology 2007 Apr 10;360(2):376-87.
        doi: 10.1016/j.virol.2006.10.049pubmed: 17156813google scholar: lookup
      13. Smith ME, Koser M, Xiao S, Siler C, McGettigan JP, Calkins C, Pomerantz RJ, Dietzschold B, Schnell MJ. Rabies virus glycoprotein as a carrier for anthrax protective antigen. Virology 2006 Sep 30;353(2):344-56.
        doi: 10.1016/j.virol.2006.05.010pubmed: 16820183google scholar: lookup
      14. Thomas CE, Zhu W, Van Dam CN, Davis NL, Johnston RE, Sparling PF. Vaccination of mice with gonococcal TbpB expressed in vivo from Venezuelan equine encephalitis viral replicon particles. Infect Immun 2006 Mar;74(3):1612-20.
      15. Volkova E, Gorchakov R, Frolov I. The efficient packaging of Venezuelan equine encephalitis virus-specific RNAs into viral particles is determined by nsP1-3 synthesis. Virology 2006 Jan 20;344(2):315-27.
        doi: 10.1016/j.virol.2005.09.010pubmed: 16239019google scholar: lookup
      16. Barth H, Aktories K, Popoff MR, Stiles BG. Binary bacterial toxins: biochemistry, biology, and applications of common Clostridium and Bacillus proteins. Microbiol Mol Biol Rev 2004 Sep;68(3):373-402, table of contents.