FREE SHIPPING over $40
OVER 9000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
Home / Equine Research Bank / PeerJ / Passive protection against anthrax in mice with plasma deriv...
PeerJ2017; 5; e3907; doi: 10.7717/peerj.3907

Passive protection against anthrax in mice with plasma derived from horses hyper-immunized against Bacillus anthracis Sterne strain.

Abstract: In this study, equine source polyclonal anti-Bacillus anthracis immunoglobulins were generated and utilized to demonstrate passive protection of mice in a lethal challenge assay. Four horses were hyper-immunized with B. anthracis Sterne strain for approximately one year. The geometric mean anti-PA titer in the horses at maximal response following immunization was 1:77,936 (Log2 mean titer 16.25, SEM ± 0.25 95% CI [15.5 -17.0]). The geometric mean neutralizing titer at maximal response was 1:128 (Log2 mean titer 7, SEM ± 0.0, 95% CI 7). Treatment with hyper-immune plasma or purified immunoglobulins was successful in passively protecting A/J mice from a lethal B. anthracis Sterne strain challenge. The treatment of mice with hyper-immune plasma at time 0 h and 24 h post-infection had no effect on survival, but did significantly increase mean time to death (p < 0.0001). Mice treated with purified immunoglobulins at time 0 h and 24 h post-infection in showed significant increase in survival rate (p < 0.001). Bacterial loads in lung, liver and spleen tissue were also assessed and were not significantly different in mice treated with hyper-immune plasma from placebo treated control mice. Mice treated with purified antibodies demonstrated mean colony forming units/gram tissue fourfold less than mice receiving placebo treatment (p < 0.0001). Immunotherapeutics harvested from horses immunized against B. anthracis Sterne strain represent a rapidly induced, inexpensive and effective expansion to the arsenal of treatments against anthrax.
Get Full Text
Publication Date: 2017-12-15 PubMed ID: 29259839PubMed Central: PMC5733894DOI: 10.7717/peerj.3907Google 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.
LinkedInCopy
  • 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 studied the efficacy of using antibodies generated in horses to protect mice against infection from the bacterium Bacillus anthracis, which causes anthrax. The results indicate that this method can significantly increase the survival rate and delay time to death, suggesting that antibodies from immunized horses could form a cost-effective addition to the available treatments for anthrax.

Study Design and Methodology

Scientists used four horses to create a source of anti-Bacillus anthracis antibodies. The horses were hyper-immunized, meaning they were vaccinated intensively to produce a concentrated immune response, with Bacillus anthracis Sterne strain, a version of the bacterium specifically designed for vaccination, for approximately a year. The presence of antibodies was measured using a geometric mean titer, a statistical method used to capture a central antibody level from varying results.

Results and Findings

  • The horses’ response to the immunization was strong, producing a high geometric mean anti-PA titer, indicative of a robust antibody response to the protective antigen (PA) of the bacterium.
  • The study also found a significant neutralizing titer, meaning the antibodies produced in the horses effectively neutralized the bacterium.
  • When mice infected with the lethal Sterne strain were treated with the horse-derived hyper-immune plasma or purified antibodies, there was a marked protective effect. This protection was measured as increased survival rates and delayed time to death.
  • Treating mice with purified antibodies within 24 hours of infection resulted in significantly improved survival rates, suggesting an effective window for post-exposure treatment.
  • While there was no significant reduction in bacterial load in mice treated with hyper-immune plasma compared to untreated mice, mice treated with purified antibodies showed a fourfold decrease in bacteria levels.

Conclusions and Implications

The generated equine source polyclonal antibodies effectively protected mice from anthrax infection. This suggests that similar strategies could be employed in treating humans with anthrax, adding a potentially inexpensive and efficient tool to the currently available treatments. Further study is required to validate this approach in humans and to explore potential side effects and the optimal timing and dosing of antibody treatment.

Cite This Article

APA
Caldwell M, Hathcock T, Brock KV. (2017). Passive protection against anthrax in mice with plasma derived from horses hyper-immunized against Bacillus anthracis Sterne strain. PeerJ, 5, e3907. https://doi.org/10.7717/peerj.3907

Publication

PeerJ
ISSN: 2167-8359
NlmUniqueID: 101603425
Country: United States
Language: English
Volume: 5
Pages: e3907

Researcher Affiliations

Caldwell, Marc
  • Department of Pathobiology, Auburn University, Auburn, AL, United States of America.
Hathcock, Terri
  • Department of Pathobiology, Auburn University, Auburn, AL, United States of America.
Brock, Kenny V
  • Edward Via College of Osteopathic Medicine, Auburn University, Auburn, AL, United States of America.

Conflict of Interest Statement

The authors declare there are no competing interests.

References

This article includes 53 references
  1. Albrecht MT, Li H, Williamson ED, LeButt CS, Flick-Smith HC, Quinn CP, Westra H, Galloway D, Mateczun A, Goldman S, Groen H, Baillie LW. Human monoclonal antibodies against anthrax lethal factor and protective antigen act independently to protect against Bacillus anthracis infection and enhance endogenous immunity to anthrax.. Infection and Immunity 2007;75:5425–5433.
    doi: 10.1128/iai.00261-07pmc: PMC2168292pubmed: 17646360google scholar: lookup
  2. Arnon SS. Creation and development of the public service orphan drug Human Botulism Immune Globulin.. Pediatrics 2007;119:785–789.
    doi: 10.1542/peds.2006-0646pubmed: 17403850google scholar: lookup
  3. Bryskier A. Bacillus anthracis and antibacterial agents.. Clinical Microbiology and Infection 2002;8:467–478.
    doi: 10.1046/j.1469-0691.2002.00527.xpubmed: 12197869google scholar: lookup
  4. Canright CM. Human anthrax and its treatment. A report of three cases.. Chinese Medical Journal 1928;42:479–496.
  5. . Use of a reduced (4-dose) vaccine schedule for postexposure prophylaxis to prevent human rabies.. 2010.
    pubmed: 20648715
  6. . Tetanus.. 2011.
  7. Chakrabarty K, Wu W, Booth JL, Duggan ES, Coggeshall KM, Metcalf JP. Bacillus anthracis spores stimulate cytokine and chemokine innate immune responses in human alveolar macrophages through multiple mitogen-activated protein kinase pathways.. Infection and Immunity 2006;74:4430–4438.
    doi: 10.1128/iai.00446-06pmc: PMC1539616pubmed: 16861629google scholar: lookup
  8. Corey A, Migone TS, Bolmer S, Fiscella M, Ward C, Chen C, Meister G. Bacillus anthracis protective antigen kinetics in inhalation spore-challenged untreated or levofloxacin/ raxibacumab-treated New Zealand white rabbits.. Toxins (Basel) 2013;5:120–138.
    doi: 10.3390/toxins5010120pmc: PMC3564073pubmed: 23344456google scholar: lookup
  9. Cui X, Li Y, Moayeri M, Choi GH, Subramanian GM, Li X, Haley M, Fitz Y, Feng J, Banks SM, Leppla SH, Eichacker PQ. Late treatment with a protective antigen-directed monoclonal antibody improves hemodynamic function and survival in a lethal toxin-infused rat model of anthrax sepsis.. Journal of Infectious Diseases 2005;191:422–434.
    doi: 10.1086/427189pubmed: 15633102google scholar: lookup
  10. Duong S, Chiaraviglio L, Kirby JE. Histopathology in a murine model of anthrax.. International Journal of Experimental Pathology 2006;87:131–137.
    doi: 10.1111/j.0959-9673.2006.00473.xpmc: PMC2517355pubmed: 16623757google scholar: lookup
  11. Goossens PL. Animal models of human anthrax: the Quest for the Holy Grail.. Molecular Aspects of Medicine 2009;30:467–480.
    doi: 10.1016/j.mam.2009.07.005pubmed: 19665473google scholar: lookup
  12. Hedges AJ. Estimating the precision of serial dilutions and viable bacterial counts.. International Journal of Food Microbiology 2002;76:207–214.
    doi: 10.1016/S0168-1605(02)00022-3pubmed: 12051477google scholar: lookup
  13. Hendricks KA, Wright ME, Shadomy SV, Bradley JS, Morrow MG, Pavia AT, Rubinstein E, Holty J-EC, Messonnier NE, Smith TL, Pesik N, Treadwell TA, Bower WA, the Workgroup on Anthrax Clinical Guidelines. Centers for disease control and prevention expert panel meetings on prevention and treatment of anthrax in adults.. Emerging Infectious Diseases 2014;20:e130687.
    doi: 10.3201/eid2002.130687pmc: PMC3901462pubmed: 24447897google scholar: lookup
  14. Hering D, Thompson W, Hewetson J, Little S, Norris S, Pace-Templeton J. Validation of the anthrax lethal toxin neutralization assay.. Biologicals 2004;32:17–27.
    doi: 10.1016/j.biologicals.2003.09.003pubmed: 15026022google scholar: lookup
  15. Hewetson JF, Little SF, Ivins BE, Johnson WM, Pittman PR, Brown JE, Norris SL, Nielsen CJ. An in vivo passive protection assay for the evaluation of immunity in AVA-vaccinated individuals.. Vaccine 2008;26:4262–4266.
    doi: 10.1016/j.vaccine.2008.05.068pubmed: 18586363google scholar: lookup
  16. Hodgson H. Cutaneous Anthrax.. Lancet 1941;237:811–813.
    doi: 10.1016/S0140-6736(00)61181-9google scholar: lookup
  17. Huang E, Pillai SK, Bower WA, Hendricks KA, Guarnizo JT, Hoyle JD, Gorman SE, Boyer AE, Quinn CP, Meaney-Delman D. Antitoxin treatment of inhalation anthrax: a systematic review.. Health Security 2015;13:365–377.
    doi: 10.1089/hs.2015.0032pmc: PMC4710135pubmed: 26690378google scholar: lookup
  18. Ivins BE, Ezzell Jr JW, Jemski J, Hedlund KW, Ristroph JD, Leppla SH. Immunization studies with attenuated strains of Bacillus anthracis.. Infection and Immunity 1986;52:454–458.
    pmc: PMC261020pubmed: 3084383
  19. Ivins BE, Welkos SL, Little SF, Crumrine MH, Nelson GO. Immunization against anthrax with Bacillus anthracis protective antigen combined with adjuvants.. Infection and Immunity 1992;60:662–668.
    pmc: PMC257681pubmed: 1730501
  20. Jackson FC, Wright GG, Armstrong J. Immunization of cattle against experimental anthrax with alum-precipitated protective antigen or spore vaccine.. American Journal of Veterinary Research 1957;18:771–777.
    pubmed: 13470233
  21. Kammanadiminti S, Patnaikuni RK, Comer J, Meister G, Sinclair C, Kodihalli S. Combination therapy with antibiotics and anthrax immune globulin intravenous (AIGIV) is potentially more effective than antibiotics alone in rabbit model of inhalational anthrax.. PLOS ONE 2014;9:e106393.
    doi: 10.1371/journal.pone.0106393pmc: PMC4165586pubmed: 25226075google scholar: lookup
  22. Karginov VA, Robinson TM, Riemenschneider J, Golding B, Kennedy M, Shiloach J, Alibek K. Treatment of anthrax infection with combination of ciprofloxacin and antibodies to protective antigen of Bacillus anthracis.. FEMS Immunology and Medical Microbiology 2004;40:71–74.
    doi: 10.1016/S0928-8244(03)00302-Xpubmed: 14734189google scholar: lookup
  23. Kummerfeldt CE. Raxibacumab: potential role in the treatment of inhalational anthrax.. Infection and Drug Resistance 2014;7:101–109.
    doi: 10.2147/idr.s47305pmc: PMC4011807pubmed: 24812521google scholar: lookup
  24. Langel FD, Chiang CY, Lane D, Kenny T, Ojeda JF, Zhong Y, Che J, Zhou Y, Ribot W, Kota KP, Bavari S, Panchal RG. Alveolar macrophages infected with Ames or Sterne strain of Bacillus anthracis elicit differential molecular expression patterns.. PLOS ONE 2014;9:e87201.
    doi: 10.1371/journal.pone.0087201pmc: PMC3917846pubmed: 24516547google scholar: lookup
  25. Leysath CE, Chen KH, Moayeri M, Crown D, Fattah R, Chen Z, Das SR, Purcell RH, Leppla SH. Mouse monoclonal antibodies to anthrax edema factor protect against infection.. Infection and Immunity 2011;79:4609–4616.
    doi: 10.1128/iai.05314-11pmc: PMC3257937pubmed: 21911463google scholar: lookup
  26. Little SF, Knudson GB. Comparative efficacy of Bacillus anthracis live spore vaccine and protective antigen vaccine against anthrax in the guinea pig.. Infection and Immunity 1986;52:509–512.
    pmc: PMC261029pubmed: 3084385
  27. Mazumdar S. Raxibacumab.. MAbs 2009;1:531–538.
    doi: 10.4161/mabs.1.6.10195pmc: PMC2791309pubmed: 20068396google scholar: lookup
  28. Migone TS, Bolmer S, Zhong J, Corey A, Vasconcelos D, Buccellato M, Meister G. Added benefit of raxibacumab to antibiotic treatment of inhalational anthrax.. Antimicrobial Agents and Chemotherapy 2015;59:1145–1151.
    doi: 10.1128/aac.04606-14pmc: PMC4335881pubmed: 25487792google scholar: lookup
  29. Migone TS, Subramanian GM, Zhong J, Healey LM, Corey A, Devalaraja M, Lo L, Ullrich S, Zimmerman J, Chen A, Lewis M, Meister G, Gillum K, Sanford D, Mott J, Bolmer SD. Raxibacumab for the treatment of inhalational anthrax.. New England Journal of Medicine 2009;361:135–144.
    doi: 10.1056/NEJMoa0810603pubmed: 19587338google scholar: lookup
  30. Mitchell W. Case of cutaneous anthrax treated without excision with sclavo’s anti-anthrax serum: recovery.. British Medical Journal 1905;2:118–120.
    pmc: PMC2321607pubmed: 20762205
  31. Moayeri M, Leppla SH, Vrentas C, Pomerantsev AP, Liu S. Anthrax pathogenesis.. Annual Review of Microbiology 2015;69:185–208.
    doi: 10.1146/annurev-micro-091014-104523pubmed: 26195305google scholar: lookup
  32. Mytle N, Hopkins RJ, Malkevich NV, Basu S, Meister GT, Sanford DC, Comer JE, Van Zandt KE, Al-Ibrahim M, Kramer WG, Howard C, Daczkowski N, Chakrabarti AC, Ionin B, Nabors GS, Skiadopoulos MH. Evaluation of intravenous anthrax immune globulin for treatment of inhalation anthrax.. Antimicrobial Agents and Chemotherapy 2013;57:5684–5692.
    doi: 10.1128/aac.00458-13pmc: PMC3811278pubmed: 23979731google scholar: lookup
  33. Oscherwitz J, Feldman D, Yu F, Cease KB. Epitope-focused peptide immunogens in human use adjuvants protect rabbits from experimental inhalation anthrax.. Vaccine 2015;33:430–436.
    doi: 10.1016/j.vaccine.2014.11.042pmc: PMC4391504pubmed: 25454087google scholar: lookup
  34. Pezard C, Berche P, Mock M. Contribution of individual toxin components to virulence of Bacillus anthracis.. Infection and Immunity 1991;59:3472–3477.
    pmc: PMC258908pubmed: 1910002
  35. Pillai SK, Huang E, Guarnizo JT, Hoyle JD, Katharios-Lanwermeyer S, Turski TK, Bower WA, Hendricks KA, Meaney-Delman D. Antimicrobial treatment for systemic anthrax: analysis of cases from 1945 to 2014 identified through a systematic literature review.. Health Security 2015;13:355–364.
    doi: 10.1089/hs.2015.0033pmc: PMC4710510pubmed: 26623698google scholar: lookup
  36. Pohl MA, Rivera J, Nakouzi A, Chow SK, Casadevall A. Combinations of monoclonal antibodies to anthrax toxin manifest new properties in neutralization assays.. Infection and Immunity 2013;81:1880–1888.
    doi: 10.1128/iai.01328-12pmc: PMC3676002pubmed: 23509144google scholar: lookup
  37. Ragazzi CA. Achille Sclavo, teacher and precursor of current preventive medicine.. Annali della Sanita Pubblica 1954;15:453–461.
    pubmed: 13229178
  38. Remy KE, Cui X, Li Y, Sun J, Solomon SB, Fitz Y, Barochia AV, Al-Hamad M, Moayeri M, Leppla SH, Eichacker PQ. Raxibacumab augments hemodynamic support and improves outcomes during shock with B. anthracis edema toxin alone or together with lethal toxin in canines.. Intensive Care Medicine Experimental 2015;3:9–23.
    doi: 10.1186/s40635-015-0043-4pmc: PMC4473792pubmed: 26097803google scholar: lookup
  39. Romanov GI. Preparation, control and application of anthrax vaccine in USSR.. Archiv Fur Experimentelle Veterinarmedizin 1980;34:119–122.
    pubmed: 6774689
  40. Santee HE. Anthrax and its treatment.. Annals of Surgery 1923;78:326–331.
    doi: 10.1097/00000658-192309000-00003pmc: PMC1400435pubmed: 17864896google scholar: lookup
  41. Sclavo A. Serum treatment of anthrax in man.. Revista d’Igiene e Sanità 1954;14:161–175.
  42. Staats HF, Alam SM, Scearce RM, Kirwan SM, Zhang JX, Gwinn WM, Haynes BF. In vitro and in vivo characterization of anthrax anti-protective antigen and anti-lethal factor monoclonal antibodies after passive transfer in a mouse lethal toxin challenge model to define correlates of immunity.. Infection and Immunity 2007;75:5443–5452.
    doi: 10.1128/iai.00529-07pmc: PMC2168269pubmed: 17709410google scholar: lookup
  43. Taft SC, Weiss AA. Neutralizing activity of vaccine-induced antibodies to two Bacillus anthracis toxin components, lethal factor and edema factor.. Clinical and Vaccine Immunology 2008;15:71–75.
    doi: 10.1128/cvi.00321-07pmc: PMC2223847pubmed: 18032590google scholar: lookup
  44. Turnbull PC, Broster MG, Carman JA, Manchee RJ, Melling J. Development of antibodies to protective antigen and lethal factor components of anthrax toxin in humans and guinea pigs and their relevance to protective immunity.. Infection and Immunity 1986;52:356–363.
    pmc: PMC261006pubmed: 3084381
  45. Turnbull PC, Leppla SH, Broster MG, Quinn CP, Melling J. Antibodies to anthrax toxin in humans and guinea pigs and their relevance to protective immunity.. Medical Microbiology and Immunology 1988;177:293–303.
    pubmed: 3139974
  46. United States Food and Drug Administration (US-FDA). Raxibacumab for anthrax.. Medical Letter on Drugs and Therapeutics 2013;55:27–28.
    pubmed: 23545582
  47. United States Food and Drug Administration (US-FDA). FDA approves treatment for inhalation anthrax.. 2015.
  48. Von Behring E. Serum therapy in therapeutics and medical science. 2008 Nobel Lecture. December 12, 1901.. .
  49. Von Stabsarzt B. Über das zustandekommen der diphtherie-immunität und der tetanus-immunität bei thieren.. Molecular Immunology 1991;28:1319–1320.
    doi: 10.1016/0161-5890(91)90033-Gpubmed: 1749380google scholar: lookup
  50. Weiss S, Kobiler D, Levy H, Pass A, Ophir Y, Rothschild N, Tal A, Schlomovitz J, Altboum Z. Antibiotics cure anthrax in animal models.. Antimicrobial Agents and Chemotherapy 2011;55:1533–1542.
    doi: 10.1128/aac.01689-10pmc: PMC3067169pubmed: 21263056google scholar: lookup
  51. Welkos SL, Friedlander AM. Comparative safety and efficacy against Bacillus anthracis of protective antigen and live vaccines in mice.. Microbial Pathogenesis 1988;5:127–139.
    doi: 10.1016/0882-4010(88)90015-0pubmed: 3148815google scholar: lookup
  52. Welkos SL, Keener TJ, Gibbs PH. Differences in susceptibility of inbred mice to Bacillus anthracis.. Infection and Immunity 1986;51:795–800.
    pmc: PMC260968pubmed: 3081444
  53. Wright JG, Quinn CP, Shadomy S, Messonnier N. Use of anthrax vaccine in the United States: recommendations of the Advisory Committee on Immunization Practices (ACIP), 2009.. MMWR Recommendations and Reports 2010;59:1–30.
    pubmed: 20651644

Citations

This article has been cited 0 times.
Subscribe to our newsletter
Join 99,103 horse owners like you who receive our email updates on horse health and nutrition.