570
Views
8
CrossRef citations to date
0
Altmetric
Review

Anthrax prevention through vaccine and post-exposure therapy

, , , , ORCID Icon &
Pages 1405-1425 | Received 16 Dec 2019, Accepted 23 Jul 2020, Published online: 24 Aug 2020

References

  • WHO. Anthrax in humans and animals. 2008 [cited 2015 Aug 14]. Available from: https://www.ncbi.nlm.nih.gov/pubmed/26269867?dopt=Citation; https://www.who.int/csr/resources/publications/anthrax_webs.pdf
  • Shadomy S, El Idrissi A, Raizman E, et al. Anthrax outbreaks: a warning for improved prevention, control and heightened awareness. Empres watch. 2016. p. 8. Available from: http://www.fao.org/3/a-i6124e.pdf
  • Hoffmaster AR, Ravel J, Rasko DA, et al. Identification of anthrax toxin genes in a Bacillus cereus associated with an illness resembling inhalation anthrax. Proc Natl Acad Sci U S A. 2004 Jun 1;101(22):8449–8454.
  • Van der Auwera GA, Andrup L, Mahillon J. Conjugative plasmid pAW63 brings new insights into the genesis of the Bacillus anthracis virulence plasmid pXO2 and of the Bacillus thuringiensis plasmid pBT9727. BMC Genomics. 2005 Jul 26;6:103.
  • Kaur M, Singh S, Bhatnagar R. Anthrax vaccines: present status and future prospects. Expert Rev Vaccines. 2013 Aug;12(8):955–970.•• Review of recent anthrax vaccine work particularly after 2001.
  • Turnbull PC. Anthrax vaccines: past, present and future. Vaccine. 1991 Aug;9(8):533–539.
  • Jernigan JA, Stephens DS, Ashford DA, et al. Bioterrorism-related inhalational anthrax: the first 10 cases reported in the United States. Emerg Infect Dis. 2001 Nov-Dec;7(6):933–944.
  • Berger T, Kassirer M, Aran AA. Injectional anthrax - new presentation of an old disease. Euro Surveill. 2014 Aug 14;19(32). DOI:10.2807/1560-7917.ES2014.19.32.20877
  • Sherer K, Li Y, Cui X, et al. Lethal and edema toxins in the pathogenesis of Bacillus anthracis septic shock: implications for therapy. Am J Respir Crit Care Med. 2007 Feb;175(3):211–221.
  • Kuo SR, Willingham MC, Bour SH, et al. Anthrax toxin-induced shock in rats is associated with pulmonary edema and hemorrhage. Microb Pathog. 2008 Jun;44(6):467–472.
  • Bradley KA, Mogridge J, Mourez M, et al. Identification of the cellular receptor for anthrax toxin. Nature. 2001 Nov;414(6860):225–229. •• Identification of human PA receptor termed 'anthrax toxin receptor', and its characterization as an extracellular von Willebrand factor A domain containing type I membrane protein that  directly binds to PA.
  • Scobie HM, Rainey GJ, Bradley KA, et al. Human capillary morphogenesis protein 2 functions as an anthrax toxin receptor. Proc Natl Acad Sci U S A. 2003 Apr;100(9):5170–5174. • Identification of capillary morphogenesisgene 2 (CMG2), which displays homology to ATR/TEM8 within the VWA/I domain as another PA receptor.
  • Martchenko M, Jeong SY, Cohen SN. Heterodimeric integrin complexes containing beta1-integrin promote internalization and lethality of anthrax toxin. Proc Natl Acad Sci U S A. 2010 Aug 31;107(35):15583–15588.
  • Kintzer AF, Sterling HJ, Tang II, et al. Role of the protective antigen octamer in the molecular mechanism of anthrax lethal toxin stabilization in plasma. J Mol Biol. 2010 Jun 25;399(5):741–758.
  • Kintzer AF, Thoren KL, Sterling HJ, et al. The protective antigen component of anthrax toxin forms functional octameric complexes. J Mol Biol. 2009 Sep 25;392(3):614–629. • Describes formation of PA oligomers  in solution and its binding to LF/EF.
  • Duesbery NS, Webb CP, Leppla SH, et al. Proteolytic inactivation of MAP-kinase-kinase by anthrax lethal factor. Science. 1998 May 1;280(5364):734–737.
  • Agrawal A, Lingappa J, Leppla SH, et al. Impairment of dendritic cells and adaptive immunity by anthrax lethal toxin. Nature. 2003 Jul 17;424(6946):329–334.
  • Leppla SH. Anthrax toxin edema factor: a bacterial adenylate cyclase that increases cyclic AMP concentrations of eukaryotic cells. Proc Natl Acad Sci U S A. 1982 May;79(10):3162–3166.
  • Baillie LW. Is new always better than old?: the development of human vaccines for anthrax. Hum Vaccin. 2009 Dec;5(12):806–816.
  • O’Brien J, Friedlander A, Dreier T, et al. Effects of anthrax toxin components on human neutrophils. Infect Immun. 1985 Jan;47(1):306–310.
  • Moayeri M, Leppla SH, Vrentas C, et al. Anthrax Pathogenesis. Annu Rev Microbiol. 2015;69:185–208.
  • Guidi-Rontani C, Levy M, Ohayon H, et al. Fate of germinated Bacillus anthracis spores in primary murine macrophages. Mol Microbiol. 2001 Nov;42(4):931–938.
  • Watson LE, Kuo SR, Katki K, et al. Anthrax toxins induce shock in rats by depressed cardiac ventricular function. PloS One. 2007 May 23;2(5):e466.
  • Meselson M, Guillemin J, Hugh-Jones M, et al. The Sverdlovsk anthrax outbreak of 1979. Science. 1994 Nov 18;266(5188):1202–1208.
  • Keim P, Smith KL, Keys C, et al. Molecular investigation of the Aum Shinrikyo anthrax release in Kameido, Japan. J Clin Microbiol. 2001 Dec;39(12):4566–4567.
  • Borio L, Frank D, Mani V, et al. Death due to bioterrorism-related inhalational anthrax: report of 2 patients. JAMA. 2001 Nov 28;286(20):2554–2559.
  • Xu W, Ohanjanian L, Sun J, et al. A systematic review and meta-analysis of preclinical trials testing anti-toxin therapies for B. anthracis infection: A need for more robust study designs and results. PloS One. 2017;12(8):e0182879.
  • Vietri NJ. Does anthrax antitoxin therapy have a role in the treatment of inhalational anthrax? Curr Opin Infect Dis. 2018 Jun;31(3):257–262.
  • Tournier JN, Rougeaux C, Biot FV, et al. Questionable Efficacy of Therapeutic Antibodies in the Treatment of Anthrax. mSphere. 2019 Jun 19;4(3). DOI:10.1128/mSphere.00282-19
  • Auerbach S, Wright GG. Studies on immunity in anthrax. VI. Immunizing activity of protective antigen against various strains of Bacillus anthracis. J Iimmunol. 1955 Aug;75(2):129–133.• Showed PA immunization can protect rabbits from challenge with various B. anthracis strains.
  • Puziss M, Wright GG. Studies on immunity in anthrax. X. Gel-adsorbed protective antigen for immunization of man. J Bacteriol. 1963 Jan;85:230–236.
  • WHO. Information sheet observed rate of vaccine reactions anthrax vaccines to humans. Global Vaccine Safety, Immunization, Vaccines and Biologicals. 2012. Available from: https://www.who.int/vaccine_safety/initiative/tools/Anthrax_Vaccine_rates_information_sheet.pdf?ua=1
  • Bower WA, Hendricks K, Pillai S, et al. Clinical framework and medical countermeasure use during an anthrax mass-casualty incident. MMWR Recomm Rep. 2015 Dec 4;64(4):1–22.•• Current recommendations for anthrax treatment.
  • PortonBiopharma. ANTHRAX VACCINE. Available from: https://www.portonbiopharma.com/products-2/anthrax-vaccine/
  • Klinman DM, Currie D, Lee G, et al. Systemic but not mucosal immunity induced by AVA prevents inhalational anthrax. Microbes Infect. 2007 Oct;9(12–13):1478–1483.• Shows the key role of AVA elicited systemic immunity in protection from inhalation anthrax.
  • Little SF, Leppla SH, Cora E. Production and characterization of monoclonal antibodies to the protective antigen component of Bacillus anthracis toxin. Infect Immun. 1988 Jul;56(7):1807–1813.
  • Rosovitz MJ, Schuck P, Varughese M, et al. Alanine-scanning mutations in domain 4 of anthrax toxin protective antigen reveal residues important for binding to the cellular receptor and to a neutralizing monoclonal antibody. J Biol Chem. 2003 Aug 15;278(33):30936–30944.
  • Laffly E, Danjou L, Condemine F, et al. Selection of a macaque Fab with framework regions like those in humans, high affinity, and ability to neutralize the protective antigen (PA) of Bacillus anthracis by binding to the segment of PA between residues 686 and 694. Antimicrob Agents Chemother. 2005 Aug;49(8):3414–3420.
  • Kelly-Cirino CD, Mantis NJ. Neutralizing monoclonal antibodies directed against defined linear epitopes on domain 4 of anthrax protective antigen. Infect Immun. 2009 Nov;77(11):4859–4867.
  • Chen Z, Moayeri M, Zhou YH, et al. Efficient neutralization of anthrax toxin by chimpanzee monoclonal antibodies against protective antigen. J Infect Dis. 2006 Mar 1;193(5):625–633.
  • Greig SL. Obiltoxaximab: first global approval. Drugs. 2016 May;76(7):823–830.
  • Hou AW, Morrill AM. Obiltoxaximab: adding to the treatment Arsenal for Bacillus anthracis infection. Ann Pharmacother. 2017 Oct;51(10):908–913.
  • Mazumdar S. Raxibacumab. MAbs. 2009 Nov-Dec;1(6):531–538.
  • Biron B, Beck K, Dyer D, et al. Efficacy of ETI-204 monoclonal antibody as an adjunct therapy in a New Zealand white rabbit partial survival model for inhalational anthrax. Antimicrob Agents Chemother. 2015 Apr;59(4):2206–2214.
  • FDA. FDA approves treatment for inhalation anthrax. 2015. Available from: https://wayback.archive-it.org/7993/20170722113813/https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm439752.htm
  • Administration USFaD. Raxibacumab. Human Genome Sciences. 2012 [cited 2019 Oct 12]. Available from: http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/125349s000lbl.pdf.
  • Head BM, Rubinstein E, Meyers AF. Alternative pre-approved and novel therapies for the treatment of anthrax. BMC Infect Dis. 2016 Nov 3;16(1):621.
  • Stanimirovic DB, Sandhu JK, Costain WJ. Emerging technologies for delivery of biotherapeutics and gene therapy across the blood-brain barrier. BioDrugs. 2018 Dec;32(6):547–559.
  • Klinman DM, Yamamoto M, Tross D, et al. Anthrax prevention and treatment: utility of therapy combining antibiotic plus vaccine. Expert Opin Biol Ther. 2009 Dec;9(12):1477–1486.
  • Chitlaru T, Altboum Z, Reuveny S, et al. Progress and novel strategies in vaccine development and treatment of anthrax. Immunol Rev. 2011 Jan;239(1):221–236.
  • Smith KA. Louis pasteur, the father of immunology? Front Immunol. 2012;3:68.
  • Pasteur L, Chamberland R. Summary report of the experiments conducted at Pouilly-le-Fort, near Melun, on the anthrax vaccination, 1881. Yale J Biol Med. 2002 Jan-Feb;75(1):59–62.
  • Sterne M. The use of anthrax vaccines prepared from avirulent (uncapsulated) variants of Bacillus anthracis. Onderstepoort J Vet Sci Anim Indust. 1939 Oct;13(2):307–312.
  • Chitlaru T, Israeli M, Bar-Haim E, et al. Next-Generation Bacillus anthracis Live Attenuated Spore Vaccine Based on the htrA- (High Temperature Requirement A) Sterne Strain. Sci Rep. 2016;6(1):18908.
  • Chitlaru T, Israeli M, Rotem S, et al. A novel live attenuated anthrax spore vaccine based on an acapsular Bacillus anthracis Sterne strain with mutations in the htrA, lef and cya genes. Vaccine. 2017 Oct 20;35(44):6030–6040.
  • Glinert I, Weiss S, Sittner A, et al. Infection with a nonencapsulated bacillus anthracis strain in rabbits-the role of bacterial adhesion and the potential for a safe live attenuated vaccine. Toxins (Basel). 2018 Dec 1;10(12). DOI:10.3390/toxins10120506
  • Pomerantsev AP, McCall RM, Chahoud M, et al. Genome engineering in Bacillus anthracis using tyrosine site-specific recombinases. PloS One. 2017;12(8):e0183346.
  • Wang Y, Wang D, Wang X, et al. Highly efficient genome engineering in Bacillus anthracis and Bacillus cereus using the CRISPR/Cas9 system. Front Microbiol. 2019;10:1932.• • Describes a method to edit the genomic DNA of B. anthracis and B. cereus using the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein (Cas)9 system. It could be developed to generate marker-free live anthrax vaccines.
  • Osorio M, Wu Y, Singh S, et al. Anthrax protective antigen delivered by Salmonella enterica serovar Typhi Ty21a protects mice from a lethal anthrax spore challenge. Infect Immun. 2009 Apr;77(4):1475–1482.
  • Sim BKL, Li M, Osorio M, et al. Protection against inhalation anthrax by immunization with Salmonella enterica serovar Typhi Ty21a stably producing protective antigen of Bacillus anthracis. NPJ Vaccines. 2017 Jun;2:17.
  • Vigonsky E, Fish I, Livnat-Levanon N, et al. Metal binding spectrum and model structure of the Bacillus anthracis virulence determinant MntA. Metallomics. 2015 Oct;7(10):1407–1419.
  • Gat O, Mendelson I, Chitlaru T, et al. The solute-binding component of a putative Mn(II) ABC transporter (MntA) is a novel Bacillus anthracis virulence determinant. Mol Microbiol. 2005 Oct;58(2):533–551.
  • Koehler SM, Buyuk F, Celebi O, et al. Protection of farm goats by combinations of recombinant peptides and formalin inactivated spores from a lethal Bacillus anthracis challenge under field conditions. BMC Vet Res. 2017 Jul 12;13(1):220.
  • Ndumnego OC, Koehler SM, Crafford JE, et al. Immunogenicity of anthrax recombinant peptides and killed spores in goats and protective efficacy of immune sera in A/J mouse model. Sci Rep. 2018 Nov 16;8(1):16937.
  • Vergis JM, Cote CK, Bozue J, et al. Immunization of mice with formalin-inactivated spores from avirulent Bacillus cereus strains provides significant protection from challenge with Bacillus anthracis Ames. Clin Vaccin Immunol. 2013 Jan;20(1):56–65.
  • Aziz MA, Singh S, Anand Kumar P, et al. Expression of protective antigen in transgenic plants: a step towards edible vaccine against anthrax. Biochem Biophys Res Commun. 2002 Dec 6;299(3):345–351.• Reports for the first time expression of PA gene in a plant system and marks the first milestone towards developing an edible anthrax vaccine.
  • Aziz MA, Sikriwal D, Singh S, et al. Transformation of an edible crop with the pagA gene of Bacillus anthracis. Faseb J. 2005 Sep;19(11):1501–1503.
  • Koya V, Moayeri M, Leppla SH, et al. Plant-based vaccine: mice immunized with chloroplast-derived anthrax protective antigen survive anthrax lethal toxin challenge. Infect Immun. 2005 Dec;73(12):8266–8274.
  • Gorantala J, Grover S, Rahi A, et al. Generation of protective immune response against anthrax by oral immunization with protective antigen plant-based vaccine. J Biotechnol. 2014 Apr176:1–10.
  • Davod J, Fatemeh DN, Honari H, et al. Constructing and transient expression of a gene cassette containing edible vaccine elements and shigellosis, anthrax and cholera recombinant antigens in tomato. Mol Biol Rep. 2018 Dec;45(6):2237–2246.
  • Radha C, Salotra P, Bhat R, et al. Thermostabilization of protective antigen–the binding component of anthrax lethal toxin. J Biotechnol. 1996 Oct 1;50(2–3):235–242.
  • Singh S, Ahuja N, Chauhan V, et al. Gln277 and Phe554 residues are involved in thermal inactivation of protective antigen of Bacillus anthracis. Biochem Biophys Res Commun. 2002 Sep 6;296(5):1058–1062.
  • Singh S, Aziz MA, Khandelwal P, et al. The osmoprotectants glycine and its methyl derivatives prevent the thermal inactivation of protective antigen of Bacillus anthracis. Biochem Biophys Res Commun. 2004 Apr 2;316(2):559–564.
  • Powell BS, Enama JT, Ribot WJ, et al. Multiple asparagine deamidation of Bacillus anthracis protective antigen causes charge isoforms whose complexity correlates with reduced biological activity. Proteins. 2007 Aug 1;68(2):458–479.
  • D’Souza AJ, Mar KD, Huang J, et al. Rapid deamidation of recombinant protective antigen when adsorbed on aluminum hydroxide gel correlates with reduced potency of vaccine. J Pharm Sci. 2013 Feb;102(2):454–461.
  • Verma A, Ngundi MM, Burns DL. Mechanistic analysis of the effect of deamidation on the immunogenicity of anthrax protective antigen. Clin vaccin immunol. 2016 May;23(5):396–402.• Shows modification/mutation of deamidation prone Asn to  deamidation-resistant amino acids improves the stability of rPA-based anthrax vaccines.
  • Verma A, Burns DL. Improving the stability of recombinant anthrax protective antigen vaccine. Vaccine. 2018 Oct 15;36(43):6379–6382.
  • Singh S, Singh A, Aziz MA, et al. Thermal inactivation of protective antigen of Bacillus anthracis and its prevention by polyol osmolytes. Biochem Biophys Res Commun. 2004 Sep 24;322(3):1029–1037.
  • Zomber G, Reuveny S, Garti N, et al. Effects of spontaneous deamidation on the cytotoxic activity of the Bacillus anthracis protective antigen. J Biol Chem. 2005 Dec 2;280(48):39897–39906.
  • Bellanti JA, Lin FY, Chu C, et al. Phase 1 study of a recombinant mutant protective antigen of Bacillus anthracis. Clin vaccin immunol. 2012 Feb;19(2):140–145.
  • Mamillapalli S, Miyagi M, Bann JG. Stability of domain 4 of the anthrax toxin protective antigen and the effect of the VWA domain of CMG2 on stability. Protein Sci. 2017 Feb;26(2):355–364.
  • Yin Y, Yu W, Li Y, et al. Self-conjugated protective antigen elicits strong and durable protective antibody response against anthrax. Int J Biol Macromol. 2019 Sep 15;137:790–800.• Describes structure preservation of PA through conjugation  as a means to improve the stability of vaccine without compromising its capacity to elicit a protective immune response.
  • Jones RM, Burke M, Dubose D, et al. Stability and pre-formulation development of a plant-produced anthrax vaccine candidate. Vaccine. 2017 Oct 4;35(41):5463–5470.
  • GlobeNewswire. Altimmune Announces Pre-Clinical Data From its SparVax-L Anthrax Vaccine Program GAITHERSBURG, Md.. GLOBE NEWSWIRE; 2018 [cited 2019 Oct 10]. Available from: https://www.globenewswire.com/news-release/2018/03/12/1420914/0/en/Altimmune-Announces-Pre-Clinical-Data-From-its-SparVax-L-Anthrax-Vaccine-Program.html
  • Chun JH, Choi OJ, Cho MH, et al. Serological correlate of protection in guinea pigs for a recombinant protective antigen anthrax vaccine produced from bacillus brevis. Osong Public Health Res Perspect. 2013 Sep;3(3):170–176.
  • Kang CK, Kim NH, Kim CJ, et al. Immunogenicity and safety of a novel recombinant protective antigen anthrax vaccine (GC1109), a randomized, single-blind, placebo controlled phase II clinical study. Vaccine. 2019 Jun 27;37(29):3820–3824.
  • Flick-Smith HC, Walker NJ, Gibson P, et al. A recombinant carboxy-terminal domain of the protective antigen of Bacillus anthracis protects mice against anthrax infection. Infect Immun. 2002 Mar;70(3):1653–1656.
  • Abboud N, Casadevall A. Immunogenicity of Bacillus anthracis protective antigen domains and efficacy of elicited antibody responses depend on host genetic background. Clin vaccin immunol. 2008 Jul;15(7):1115–1123.
  • Martin TL, Jee J, Kim E, et al. Sublingual targeting of STING with 3ʹ3’-cGAMP promotes systemic and mucosal immunity against anthrax toxins. Vaccine. 2017 Apr 25;35(18):2511–2519.
  • Minang JT, Inglefield JR, Harris AM, et al. Enhanced early innate and T cell-mediated responses in subjects immunized with Anthrax Vaccine Adsorbed Plus CPG 7909 (AV7909). Vaccine. 2014 Nov 28;32(50):6847–6854.
  • Hopkins RJ, Kalsi G, Montalvo-Lugo VM, et al. Randomized, double-blind, active-controlled study evaluating the safety and immunogenicity of three vaccination schedules and two dose levels of AV7909 vaccine for anthrax post-exposure prophylaxis in healthy adults. Vaccine. 2016 Apr 19;34(18):2096–2105.
  • Savransky V, Shearer JD, Gainey MR, et al. Correlation between anthrax lethal toxin neutralizing antibody levels and survival in guinea pigs and nonhuman primates vaccinated with the AV7909 anthrax vaccine candidate. Vaccine. 2017 Sep 5;35(37):4952–4959.
  • ClinicalTrials.gov. VELOCITY: an anthrax vaccine clinical study. 2019 [ updated 2019 Jul 10; cited 2019 Oct 10]. Available from: https://clinicaltrials.gov/ct2/show/NCT03877926
  • ClinicalTrials.gov. BARDA Securing Anthrax Immunity For the Elderly (B-SAFE). 2018 [updated 2019 Mar 20; 2019 Oct 10]. Available from: https://clinicaltrials.gov/ct2/show/NCT03518125
  • Autumn Smiley M, Sanford DC, Triplett CA, et al. Comparative immunogenicity and efficacy of thermostable (lyophilized) and liquid formulation of anthrax vaccine candidate AV7909. Vaccine. 2019 Oct 8;37(43):6356–6361.
  • Jelacic TM, Chabot DJ, Bozue JA, et al. Exposure to Bacillus anthracis capsule results in suppression of human monocyte-derived dendritic cells. Infect Immun. 2014 Aug;82(8):3405–3416.
  • Jeon JH, Park DB, Woo SJ, et al. Muramyl dipeptide potentiates a Bacillus anthracis poly-gamma-d-glutamic acid capsule surrogate that induces maturation and activation of mouse dendritic cells. Cytokine. 2018 Oct;110:350–356.
  • Lee HR, Jeon JH, Rhie GE. The Poly-gamma-D-Glutamic Acid Capsule of Bacillus licheniformis, a Surrogate of Bacillus anthracis Capsule Induces Interferon-Gamma Production in NK Cells through Interactions with Macrophages. J Microbiol Biotechnol. 2017 May 28;27(5):1032–1037.
  • Rhie GE, Roehrl MH, Mourez M, et al. A dually active anthrax vaccine that confers protection against both bacilli and toxins. Proc Natl Acad Sci U S A. 2003 Sep 16;100(19):10925–10930.
  • Chabot DJ, Ribot WJ, Joyce J, et al. Protection of rhesus macaques against inhalational anthrax with a Bacillus anthracis capsule conjugate vaccine. Vaccine. 2016 Jul 25;34(34):4012–4016.
  • Cote CK, Kaatz L, Reinhardt J, et al. Characterization of a multi-component anthrax vaccine designed to target the initial stages of infection as well as toxaemia. J Med Microbiol. 2012 Oct;61(Pt 10):1380–1392.• • Describes the generation and evaluation of a multi-component anthrax vaccine comprising of PA and other recombinant spore-surface antigens to effectively target different stages of anthrax.
  • Liu X, Wang D, Ren J, et al. Identification of the immunogenic spore and vegetative proteins of Bacillus anthracis vaccine strain A16R. PloS One. 2013;8(3):e57959.
  • Kim YH, Kim KA, Kim YR, et al. Immunoproteomically identified GBAA_0345, alkyl hydroperoxide reductase subunit C is a potential target for multivalent anthrax vaccine. Proteomics. 2014 Jan;14(1):93–104.
  • Kempsell KE, Kidd SP, Lewandowski K, et al. Whole genome protein microarrays for serum profiling of immunodominant antigens of Bacillus anthracis. Front Microbiol. 2015;6:747.
  • Chitlaru T, Gat O, Grosfeld H, et al. Identification of in vivo-expressed immunogenic proteins by serological proteome analysis of the Bacillus anthracis secretome. Infect Immun. 2007 Jun;75(6):2841–2852.
  • Gat O, Grosfeld H, Ariel N, et al. Search for Bacillus anthracis potential vaccine candidates by a functional genomic-serologic screen. Infect Immun. 2006 Jul;74(7):3987–4001.
  • Ariel N, Zvi A, Makarova KS, et al. Genome-based bioinformatic selection of chromosomal Bacillus anthracis putative vaccine candidates coupled with proteomic identification of surface-associated antigens. Infect Immun. 2003 Aug;71(8):4563–4579.
  • Keitel WA, Treanor JJ, El Sahly HM, et al. Evaluation of a plasmid DNA-based anthrax vaccine in rabbits, nonhuman primates and healthy adults. Hum Vaccin. 2009 Aug;5(8):536–544.
  • Midha S, Bhatnagar R. Anthrax protective antigen administered by DNA vaccination to distinct subcellular locations potentiates humoral and cellular immune responses. Eur J Immunol. 2009 Jan;39(1):159–177.
  • Midha S, Bhatnagar R. Genetic immunization with GPI-anchored anthrax protective antigen raises combined CD1d- and MHC II-restricted antibody responses by natural killer T cell-mediated help. Vaccine. 2009 Mar 10;27(11):1700–1709.
  • Livingston BD, Little SF, Luxembourg A, et al. Comparative performance of a licensed anthrax vaccine versus electroporation based delivery of a PA encoding DNA vaccine in rhesus macaques. Vaccine. 2010 Jan 22;28(4):1056–1061.
  • Donate A, Heller R. Assessment of delivery parameters with the multi-electrode array for development of a DNA vaccine against Bacillus anthracis. Bioelectrochemistry. 2013 Dec;94:1–6.
  • Albrecht MT, Eyles JE, Baillie LW, et al. Immunogenicity and efficacy of an anthrax/plague DNA fusion vaccine in a mouse model. FEMS Immunol Med Microbiol. 2012 Aug;65(3):505–509.
  • Albrecht MT, Livingston BD, Pesce JT, et al. Electroporation of a multivalent DNA vaccine cocktail elicits a protective immune response against anthrax and plague. Vaccine. 2012 Jul 6;30(32):4872–4883.
  • Kim NY, Chang DS, Kim Y, et al. Enhanced Immune Response to DNA Vaccine Encoding Bacillus anthracis PA-D4 Protects Mice against Anthrax Spore Challenge. PloS One. 2015;10(10):e0139671.
  • Yu YZ, Ma Y, Xu WH, et al. Combinations of various CpG motifs cloned into plasmid backbone modulate and enhance protective immunity of viral replicon DNA anthrax vaccines. Med Microbiol Immunol. 2015 Aug;204(4):481–491.
  • Wang HC, An HJ, Yu YZ, et al. Potentiation of anthrax vaccines using protective antigen-expressing viral replicon vectors. Immunol Lett. 2015 Feb;163(2):206–213.• Describes viral replicon as an efficient vector to administer PA (and other antigens) to generate immunity against anthrax.
  • Palmer J, Bell M, Darko C, et al. Protein- and DNA-based anthrax toxin vaccines confer protection in guinea pigs against inhalational challenge with Bacillus cereus G9241. Pathog Dis. 2014 Nov;72(2):138–142.• Demonstrates applicability of Protein- and DNA-based anthrax vaccines in protecting from anthrax-like illness causing other bacterial isolates.
  • Kohler SM, Baillie LW, Beyer W. BclA and toxin antigens augment each other to protect NMRI mice from lethal Bacillus anthracis challenge. Vaccine. 2015 Jun 4;33(24):2771–2777.
  • Crowe SR, Ash LL, Engler RJ, et al. Select human anthrax protective antigen epitope-specific antibodies provide protection from lethal toxin challenge. J Infect Dis. 2010 Jul 15;202(2):251–260.
  • Dumas EK, Nguyen ML, Cox PM, et al. Stochastic humoral immunity to Bacillus anthracis protective antigen: identification of anti-peptide IgG correlating with seroconversion to Lethal Toxin neutralization. Vaccine. 2013 Apr 3;31(14):1856–1863.
  • Oscherwitz J, Yu F, Cease KB. A synthetic peptide vaccine directed against the 2ss2-2ss3 loop of domain 2 of protective antigen protects rabbits from inhalation anthrax. J Iimmunol. 2010 Sep 15;185(6):3661–3668.
  • Oscherwitz J, Yu F, Jacobs JL, et al. Synthetic peptide vaccine targeting a cryptic neutralizing epitope in domain 2 of Bacillus anthracis protective antigen. Infect Immun. 2009 Aug;77(8):3380–3388.
  • Oscherwitz J, Yu F, Jacobs JL, et al. Recombinant vaccine displaying the loop-neutralizing determinant from protective antigen completely protects rabbits from experimental inhalation anthrax. Clin Vaccin Immunol. 2013 Mar;20(3):341–349.
  • Ascough S, Ingram RJ, Chu KK, et al. CD4+ T Cells targeting dominant and cryptic epitopes from Bacillus anthracis lethal factor. Front Microbiol. 2015;6:1506.
  • Balderas MA, Nguyen CTQ, Terwilliger A, et al. Progress toward the development of a NEAT protein vaccine for anthrax disease. Infect Immun. 2016 Dec;84(12):3408–3422.
  • Wu G, Hong Y, Guo A, et al. A chimeric protein that functions as both an anthrax dual-target antitoxin and a trivalent vaccine. Antimicrob Agents Chemother. 2010 Nov;54(11):4750–4757.
  • Suryanarayana N, Verma M, Thavachelvam K, et al. Generation of a novel chimeric PALFn antigen of Bacillus anthracis and its immunological characterization in mouse model. Appl Microbiol Biotechnol. 2016 Oct;100(19):8439–8451.
  • Majumder S, Das S, Somani V, et al. A bivalent protein r-PB, comprising PA and BclA immunodominant regions for comprehensive protection against Bacillus anthracis. Sci Rep. 2018 May 8;8(1):7242.
  • Majumder S, Das S, Somani VK, et al. A Bivalent Protein r-PAbxpB Comprising PA Domain IV and Exosporium Protein BxpB Confers Protection Against B. anthracis Spores and Toxin. Front Immunol. 2019;10:498.
  • Aggarwal S, Somani VK, Gupta S, et al. Development of a novel multiepitope chimeric vaccine against anthrax. Med Microbiol Immunol. 2019 Apr;208(2):185–195.• Reports multiepitope chimeric vaccine ID-LFn, comprising of ID II-ID III region of PA and N-terminal region of LF, which performs better than PA-based vaccines.
  • Varshney A, Kumar M, Nagar DP, et al. Development of a novel chimeric PA-LF antigen of Bacillus anthracis, its immunological characterization and evaluation as a future vaccine candidate in mouse model. Biologicals. 2019 Sep;61:38–43.
  • Mirhaj H, Honari H, Zamani E. Evaluation of immune response to recombinant Bacillus anthracis LFD1-PA4 chimeric protein. Iran J Vet Res. 2019 Spring;20(2):112–119.
  • Gallagher TB, Mellado-Sanchez G. Development of a multiple-antigen protein fusion vaccine candidate that confers protection against Bacillus anthracis and Yersinia pestis. PLoS Negl Trop Dis. 2019 Aug;13(8):e0007644.• Describes development of a multiple antigen dual vaccine for B. anthracis and Y. pestis.
  • Langley WA, Bradley KC, Li ZN, et al. Induction of neutralizing antibody responses to anthrax protective antigen by using influenza virus vectors: implications for disparate immune system priming pathways. J Virol. 2010 Aug;84(16):8300–8307.
  • McConnell MJ, Hanna PC, Imperiale MJ. Adenovirus-based prime-boost immunization for rapid vaccination against anthrax. Mol Ther. 2007 Jan;15(1):203–210.
  • Santra S, Seaman MS, Xu L, et al. Replication-defective adenovirus serotype 5 vectors elicit durable cellular and humoral immune responses in nonhuman primates. J Virol. 2005 May;79(10):6516–6522.
  • Fernandez E, Toledo JR, Chiong M, et al. Single dose adenovirus vectored vaccine induces a potent and long-lasting immune response against rabbit hemorrhagic disease virus after parenteral or mucosal administration. Vet Immunol Immunopathol. 2011 Aug 15;142(3–4):179–188.
  • Hu RL, Liu Y, Zhang SF, et al. Experimental immunization of cats with a recombinant rabies-canine adenovirus vaccine elicits a long-lasting neutralizing antibody response against rabies. Vaccine. 2007 Jul 20;25(29):5301–5307.
  • Zhang J, Jex E, Feng T, et al. An adenovirus-vectored nasal vaccine confers rapid and sustained protection against anthrax in a single-dose regimen. Clin vaccin immunol. 2013 Jan;20(1):1–8.
  • Krishnan V, Andersen BH, Shoemaker C, et al. Efficacy and immunogenicity of single-dose AdVAV intranasal anthrax vaccine compared to anthrax vaccine absorbed in an aerosolized spore rabbit challenge model. Clin vaccin immunol. 2015 Apr;22(4):430–439.
  • McComb RC, Ho CL, Bradley KA, et al. Presentation of peptides from Bacillus anthracis protective antigen on Tobacco Mosaic Virus as an epitope targeted anthrax vaccine. Vaccine. 2015 Nov 27;33(48):6745–6751.
  • Kachura MA, Hickle C. A CpG-Ficoll Nanoparticle Adjuvant for Anthrax Protective Antigen Enhances Immunogenicity and Provides Single-Immunization Protection against Inhaled Anthrax in Monkeys. J Immunol. 2016 Jan 1;196(1):284–297.
  • Tao P, Mahalingam M, Zhu J, et al. A bacteriophage T4 nanoparticle-based dual vaccine against anthrax and plague. MBio. 2018 Oct 16;9:5.
  • Manish M, Rahi A, Kaur M, et al. A single-dose PLGA encapsulated protective antigen domain 4 nanoformulation protects mice against Bacillus anthracis spore challenge. PloS One. 2013;8(4):e61885.
  • Malik A, Gupta M, Mani R, et al. Trimethyl chitosan nanoparticles encapsulated protective antigen protects the mice against anthrax. Front Immunol. 2018;9:562.
  • Weir GM, MacDonald LD, Rajagopalan R, et al. Single dose of DPX-rPA, an enhanced-delivery anthrax vaccine formulation, protects against a lethal Bacillus anthracis spore inhalation challenge. NPJ Vaccines. 2019;4:6.
  • Ohanjanian L, Remy KE, Li Y, et al. An overview of investigational toxin-directed therapies for the adjunctive management of Bacillus anthracis infection and sepsis. Expert Opin Investig Drugs. 2015;24(7):851–865.
  • Lincoln RE, Klein F, Walker JS, et al. Successful Treatment of Rhesus Monkeys for Septicemia Anthrax. Antimicrob Agents Chemother (Bethesda). 1964;10:759–763.
  • Guchenour WS, Schoening HW, Stein CD, et al. Efficacy of Anthrax Biologics in Producing Immunity in Previously Unexposed Animals.Technical Bulletins 164533. United States Department of Agriculture, Economic Research Service. 1935.
  • Henderson DW, Peacock S, Belton FC. Observations on the prophylaxis of experimental pulmonary anthrax in the monkey. J Hyg (Lond). 1956 Mar;54(1):28–36.
  • Klein F, Hodges DR, Mahlandt BG, et al. Anthrax toxin: causative agent in the death of rhesus monkeys. Science. 1962 Dec 21;138(3547):1331–1333.
  • Little SF, Ivins BE, Fellows PF, et al. Passive protection by polyclonal antibodies against Bacillus anthracis infection in guinea pigs. Infect Immun. 1997 Dec;65(12):5171–5175.
  • Schneemann A, Manchester M. Anti-toxin antibodies in prophylaxis and treatment of inhalation anthrax. Future Microbiol. 2009 Feb;4(1):35–43.
  • Chen Z, Moayeri M, Purcell R. Monoclonal antibody therapies against anthrax. Toxins (Basel). 2011 Aug;3(8):1004–1019.
  • Chen Q, Davis KR The potential of plants as a system for the development and production of human biologics. F1000Research. 2016; 5.
  • Jang J, Cho M, Lee HR, et al. Monoclonal antibody against the poly-gamma-D-glutamic acid capsule of Bacillus anthracis protects mice from enhanced lethal toxin activity due to capsule and anthrax spore challenge. Biochim Biophys Acta. 2013 Mar;1830(3):2804–2812.
  • Chen Z, Moayeri M, Crown D, et al. Novel chimpanzee/human monoclonal antibodies that neutralize anthrax lethal factor, and evidence for possible synergy with anti-protective antigen antibody. Infect Immun. 2009 Sep;77(9):3902–3908.
  • Altaweel L, Chen Z, Moayeri M, et al. Delayed treatment with W1-mAb, a chimpanzee-derived monoclonal antibody against protective antigen, reduces mortality from challenges with anthrax edema or lethal toxin in rats and with anthrax spores in mice. Crit Care Med. 2011 Jun;39(6):1439–1447.
  • Xiong S, Tang Q, Liang X, et al. A Novel Chimeric Anti-PA Neutralizing Antibody for Postexposure Prophylaxis and Treatment of Anthrax. Sci Rep. 2015 Jul;2(5):11776.
  • Chen Z, Moayeri M, Zhao H, et al. Potent neutralization of anthrax edema toxin by a humanized monoclonal antibody that competes with calmodulin for edema factor binding. Proc Natl Acad Sci U S A. 2009 Aug 11;106(32):13487–13492.
  • Vitale L, Blanset D, Lowy I, et al. Prophylaxis and therapy of inhalational anthrax by a novel monoclonal antibody to protective antigen that mimics vaccine-induced immunity. Infect Immun. 2006 Oct;74(10):5840–5847.
  • Riddle V, Leese P, Blanset D, et al. Phase I study evaluating the safety and pharmacokinetics of MDX-1303, a fully human monoclonal antibody against Bacillus anthracis protective antigen, in healthy volunteers. Clin vaccin immunol. 2011 Dec;18(12):2136–2142.
  • Peterson JW, Comer JE, Noffsinger DM, et al. Human monoclonal anti-protective antigen antibody completely protects rabbits and is synergistic with ciprofloxacin in protecting mice and guinea pigs against inhalation anthrax. Infect Immun. 2006 Feb;74(2):1016–1024.
  • Malkevich NV, Hopkins RJ, Bernton E, et al. Efficacy and safety of AVP-21D9, an anthrax monoclonal antibody, in animal models and humans. Antimicrob Agents Chemother. 2014 Jul;58(7):3618–3625.
  • Albrecht MT, Li H, Williamson ED, et al. Human monoclonal antibodies against anthrax lethal factor and protective antigen act independently to protect against Bacillus anthracis infection and enhance endogenous immunity to anthrax. Infect Immun. 2007 Nov;75(11):5425–5433.
  • Rosenfeld R, Marcus H, Ben-Arie E, et al. Isolation and chimerization of a highly neutralizing antibody conferring passive protection against lethal Bacillus anthracis infection. PloS One. 2009 Jul 24;4(7):e6351.
  • Mechaly A, Levy H, Epstein E, et al. A novel mechanism for antibody-based anthrax toxin neutralization: inhibition of prepore-to-pore conversion. J Biol Chem. 2012 Sep 21;287(39):32665–32673.
  • Farcasanu M, Wang AG, Uchanski T, et al. Rapid discovery and characterization of synthetic neutralizing antibodies against anthrax edema toxin. Biochemistry. 2019 Jul 9;58(27):2996–3004.
  • Tang Q, Xiong S, Liang X, et al. Human monoclonal anti-protective antigen antibody for the low-dose post-exposure prophylaxis and treatment of Anthrax. BMC Infect Dis. 2018 Dec 10;18(1):640.
  • Wagner EK, Maynard JA. Engineering therapeutic antibodies to combat infectious diseases. Curr Opin Chem Eng. 2018 Mar;19:131–141.
  • Hull AK, Criscuolo CJ, Mett V, et al. Human-derived, plant-produced monoclonal antibody for the treatment of anthrax. Vaccine. 2005 Mar 18;23(17–18):2082–2086.
  • Hiatt A, Whaley KJ, Zeitlin L. Plant-derived monoclonal antibodies for prevention and treatment of infectious disease. Microbiol Spectr. 2014 Feb;2(1):AID-0004-2012.
  • Komarova TV, Sheshukova EV, Dorokhov YL. Plant-made antibodies: properties and therapeutic applications. Curr Med Chem. 2019;26(3):381–395.
  • Mett V, Chichester JA, Stewart ML, et al. A non-glycosylated, plant-produced human monoclonal antibody against anthrax protective antigen protects mice and non-human primates from B. anthracis spore challenge. Hum Vaccin. 2011 Jan-Feb;7(Suppl):183–190.
  • Mamedov T, Ghosh A, Jones RM, et al. Production of non-glycosylated recombinant proteins in Nicotiana benthamiana plants by co-expressing bacterial PNGase F. Plant Biotechnol J. 2012 Sep;10(7):773–782.
  • Hamers-Casterman C, Atarhouch T, Muyldermans S, et al. Naturally occurring antibodies devoid of light chains. Nature. 1993 Jun 3;363(6428):446–448.
  • Hassanzadeh-Ghassabeh G, Devoogdt N, De Pauw P, et al. Nanobodies and their potential applications. Nanomedicine. 2013 Jun;8(6):1013–1026.
  • Carlson JR. A new means of inducibly inactivating a cellular protein. Mol Cell Biol. 1988 Jun;8(6):2638–2646.
  • Hussack G, Riazi A, Ryan S, et al. Protease-resistant single-domain antibodies inhibit Campylobacter jejuni motility. Protein Eng Des Sel. 2014 Jun;27(6):191–198.
  • Adams H, Horrevoets WM, Adema SM, et al. Inhibition of biofilm formation by Camelid single-domain antibodies against the flagellum of Pseudomonas aeruginosa. J Biotechnol. 2014 Sep;30(186):66–73.
  • Nguyen VS, Logger L, Spinelli S, et al. Inhibition of type VI secretion by an anti-TssM llama nanobody. PloS One. 2015;10(3):e0122187.
  • Ardekani LS, Gargari SL, Rasooli I, et al. A novel nanobody against urease activity of Helicobacter pylori. Int J Infect Dis. 2013 Sep;17(9):e723–8.
  • Conrath KE, Lauwereys M, Galleni M, et al. Beta-lactamase inhibitors derived from single-domain antibody fragments elicited in the camelidae. Antimicrob Agents Chemother. 2001 Oct;45(10):2807–2812.
  • Shali A, Hasannia S, Gashtasbi F, et al. Generation and screening of efficient neutralizing single domain antibodies (VHHs) against the critical functional domain of anthrax protective antigen (PA). Int J Biol Macromol. 2018 Jul;15(114):1267–1278.
  • Fioravanti A, Van Hauwermeiren F, Van der Verren SE, et al. Structure of S-layer protein Sap reveals a mechanism for therapeutic intervention in anthrax. Nat Microbiol. 2019 Jul 15. DOI:10.1038/s41564-019-0499-1
  • Wycoff K, Maclean J, Belle A, et al. Anti-infective immunoadhesins from plants. Plant Biotechnol J. 2015 Oct;13(8):1078–1093.• Highlights the plants as source of anti-infective immunoadhesins for therapeutics.
  • Andrianov V, Brodzik R, Spitsin S, et al. Production of recombinant anthrax toxin receptor (ATR/CMG2) fused with human Fc in planta. Protein Expr Purif. 2010 Apr;70(2):158–162.
  • Wycoff KL, Belle A, Deppe D, et al. Recombinant anthrax toxin receptor-Fc fusion proteins produced in plants protect rabbits against inhalational anthrax. Antimicrob Agents Chemother. 2011 Jan;55(1):132–139.
  • Karuppanan K, Duhra-Gill S, Kailemia MJ, et al. Expression, purification, and biophysical characterization of a secreted anthrax decoy fusion protein in nicotiana benthamiana. Int J Mol Sci. 2017 Jan 4;18(1):89.
  • Thomas D, Naughton J, Cote C, et al. Delayed toxicity associated with soluble anthrax toxin receptor decoy-Ig fusion protein treatment. PloS One. 2012;7(4):e34611.• Highlights the delayed toxicity associated with the use of soluble PA-binding anthrax toxin receptor decoys as therapeutics.
  • Xi Y, Wu X, Gao L, et al. Improving the anti-toxin abilities of the CMG2-Fc fusion protein with the aid of computational design. PloS One. 2014;9(8):e104674.
  • PB. I. Planet Biotechnology - Recent Products. 2015 [cited 2019 Nov 11]. Available from: https://www.planetbiotechnology.com/products.html
  • Devera TS, Prusator DK, Joshi SK, et al. Immunization of mice with anthrax protective antigen limits cardiotoxicity but not hepatotoxicity following lethal toxin challenge. Toxins (Basel). 2015 Jun 25;7(7):2371–2384.
  • Weilhammer DR, Dunkle AD, Fischer NO, et al. Intranasal immunization with Bacillus anthracis spore antigens sensitizes mice to death from inhalational anthrax in a B cell-dependent manner. J Immunol. 2018;200(1Supplement): 180.22-180.22.
  • Pajewski NM, Shrestha S, Quinn CP, et al. A genome-wide association study of host genetic determinants of the antibody response to Anthrax Vaccine Adsorbed. Vaccine. 2012 Jul 6;30(32):4778–4784.
  • Ovsyannikova IG, Pankratz VS, Vierkant RA, et al. Human leukocyte antigens and cellular immune responses to anthrax vaccine adsorbed. Infect Immun. 2013 Jul;81(7):2584–2591.
  • Kulshreshtha P, Tiwari A, Priyanka, et al. Investigation of a panel of monoclonal antibodies and polyclonal sera against anthrax toxins resulted in identification of an anti-lethal factor antibody with disease-enhancing characteristics. Mol Immunol. 2015 Dec;68(2):185–193. • Reports identification of disease enhancing anti-LF antibody on immunization with recombinant N-terminal domain of LF.
  • Iyer JK, Khurana T, Langer M, et al. Inflammatory cytokine response to Bacillus anthracis peptidoglycan requires phagocytosis and lysosomal trafficking. Infect Immun. 2010 Jun;78(6):2418–2428.
  • Ingavle G, Baillie L, Davies N, et al. Bioinspired detoxification of blood: the efficient removal of anthrax toxin protective antigen using an extracorporeal macroporous adsorbent device. Sci Rep. 2018 May 14;8(1):7518.• Describes possible means of detoxification of blood in advance stage anthrax.
  • Cozens D, Read RC. Anti-adhesion methods as novel therapeutics for bacterial infections. Expert Rev Anti Infect Ther. 2012 Dec;10(12):1457–1468.• Discusses anti-adhesion methods application as therapeutics in bacterial diseases/infections.
  • Chen AY, Adamek RN, Dick BL, et al. Targeting metalloenzymes for therapeutic intervention. Chem Rev. 2019 Jan 23;119(2):1323–1455.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.