Oral Spore Vaccine Based on Live Attenuated Nontoxinogenic Bacillus Anthracis Expressing Recombinant Mutant Protective Antigen

Overview

Journal Infect Immun

Publisher American Society for Microbiology

Specialty Allergy & Immunology

Date 2005 Jun 24

PMID 15972492

Citations 15

Authors

R Aloni-Grinstein

O Gat

Z Altboum

B Velan

S Cohen

A Shafferman

Affiliations

Soon will be listed here.

Abstract

An attenuated nontoxinogenic nonencapsulated Bacillus anthracis spore vaccine expressing high levels of recombinant mutant protective antigen (PA), which upon subcutaneous immunization provided protection against a lethal B. anthracis challenge, was found to have the potential to serve also as an oral vaccine. Guinea pigs immunized per os with the recombinant spore vaccine were primed to B. anthracis vegetative antigens as well as to PA, yet only a fraction of the animals (30% to 50%) mounted a humoral response to all of these antigens. Protective immunity provided by per os immunization correlated with a threshold level of PA neutralizing antibody titers and was long-lasting. Protection conferred by per os immunization was attained when the vaccine was administered in the sporogenic form, which, unlike the vegetative cells, survived passage through the gastrointestinal tract. A comparison of immunization of unirradiated spores with immunization of gamma-irradiated spores demonstrated that germination and de novo synthesis of PA were prerequisites for mounting an immune protective response. Oral immunization of guinea pigs with attenuated B. anthracis spores resulted in a characteristic anti-PA immunoglobulin isotype profile (immunoglobulin [G1 IgG1] versus IgG2), as well as induction of specific anti-PA secretory IgA, indicating development of mucosal immunity.

Citing Articles

Immunological Evidence of Variation in Exposure and Immune Response to in Herbivores of Kruger and Etosha National Parks.

Ochai S, Crafford J, Hassim A, Byaruhanga C, Huang Y, Hartmann A Front Immunol. 2022; 13:814031.

PMID: 35237267 PMC: 8882864. DOI: 10.3389/fimmu.2022.814031.

A Comprehensive Overview on the Production of Vaccines in Plant-Based Expression Systems and the Scope of Plant Biotechnology to Combat against SARS-CoV-2 Virus Pandemics.

Kumar M, Kumari N, Thakur N, Bhatia S, Saratale G, Ghodake G Plants (Basel). 2021; 10(6).

PMID: 34203729 PMC: 8232254. DOI: 10.3390/plants10061213.

Protective antibody response following oral vaccination with microencapsulated Sterne strain 34F2 spores.

Benn Felix J, Chaki S, Xu Y, Ficht T, Rice-Ficht A, Cook W NPJ Vaccines. 2020; 5:59.

PMID: 32685200 PMC: 7351773. DOI: 10.1038/s41541-020-0208-3.

Next-Generation Bacillus anthracis Live Attenuated Spore Vaccine Based on the htrA(-) (High Temperature Requirement A) Sterne Strain.

Chitlaru T, Israeli M, Bar-Haim E, Elia U, Rotem S, Ehrlich S Sci Rep. 2016; 6:18908.

PMID: 26732659 PMC: 4702213. DOI: 10.1038/srep18908.

The Exosporium Layer of Bacterial Spores: a Connection to the Environment and the Infected Host.

Stewart G Microbiol Mol Biol Rev. 2015; 79(4):437-57.

PMID: 26512126 PMC: 4651027. DOI: 10.1128/MMBR.00050-15.

References

Pezard C, Berche P, Mock M . Contribution of individual toxin components to virulence of Bacillus anthracis. Infect Immun. 1991; 59(10):3472-7. PMC: 258908. DOI: 10.1128/iai.59.10.3472-3477.1991. View

Marcus H, Danieli R, Epstein E, Velan B, Shafferman A, Reuveny S . Contribution of immunological memory to protective immunity conferred by a Bacillus anthracis protective antigen-based vaccine. Infect Immun. 2004; 72(6):3471-7. PMC: 415724. DOI: 10.1128/IAI.72.6.3471-3477.2004. View

Duc L, Hong H, Fairweather N, Ricca E, Cutting S . Bacterial spores as vaccine vehicles. Infect Immun. 2003; 71(5):2810-8. PMC: 153275. DOI: 10.1128/IAI.71.5.2810-2818.2003. View

Little S, Ivins B, Fellows P, Friedlander A . Passive protection by polyclonal antibodies against Bacillus anthracis infection in guinea pigs. Infect Immun. 1997; 65(12):5171-5. PMC: 175745. DOI: 10.1128/iai.65.12.5171-5175.1997. View

Guillobel H, Carinhanha J, Cardenas L, Clements J, de Almeida D, Ferreira L . Adjuvant activity of a nontoxic mutant of Escherichia coli heat-labile enterotoxin on systemic and mucosal immune responses elicited against a heterologous antigen carried by a live Salmonella enterica serovar Typhimurium vaccine strain. Infect Immun. 2000; 68(7):4349-53. PMC: 101767. DOI: 10.1128/IAI.68.7.4349-4353.2000. View

Friedlander A, Welkos S, Ivins B . Anthrax vaccines. Curr Top Microbiol Immunol. 2002; 271:33-60. DOI: 10.1007/978-3-662-05767-4_3. View

McBride B, Mogg A, Telfer J, Lever M, Miller J, Turnbull P . Protective efficacy of a recombinant protective antigen against Bacillus anthracis challenge and assessment of immunological markers. Vaccine. 1998; 16(8):810-7. DOI: 10.1016/s0264-410x(97)00268-5. View

Bowman C, Clements J . Differential biological and adjuvant activities of cholera toxin and Escherichia coli heat-labile enterotoxin hybrids. Infect Immun. 2001; 69(3):1528-35. PMC: 98052. DOI: 10.1128/IAI.69.3.1528-1535.2001. View

Brossier F, Levy M, Mock M . Anthrax spores make an essential contribution to vaccine efficacy. Infect Immun. 2002; 70(2):661-4. PMC: 127709. DOI: 10.1128/IAI.70.2.661-664.2002. View

10.

Moayeri M, Leppla S . The roles of anthrax toxin in pathogenesis. Curr Opin Microbiol. 2004; 7(1):19-24. DOI: 10.1016/j.mib.2003.12.001. View

11.

Coulson N, Fulop M, Titball R . Bacillus anthracis protective antigen, expressed in Salmonella typhimurium SL 3261, affords protection against anthrax spore challenge. Vaccine. 1994; 12(15):1395-401. DOI: 10.1016/0264-410x(94)90148-1. View

12.

Gaur R, Gupta P, Banerjea A, Singh Y . Effect of nasal immunization with protective antigen of Bacillus anthracis on protective immune response against anthrax toxin. Vaccine. 2002; 20(21-22):2836-9. DOI: 10.1016/s0264-410x(02)00207-4. View

13.

Ivins B, Pitt M, Fellows P, Farchaus J, Benner G, Waag D . Comparative efficacy of experimental anthrax vaccine candidates against inhalation anthrax in rhesus macaques. Vaccine. 1998; 16(11-12):1141-8. DOI: 10.1016/s0264-410x(98)80112-6. View

14.

Barnard J, Friedlander A . Vaccination against anthrax with attenuated recombinant strains of Bacillus anthracis that produce protective antigen. Infect Immun. 1999; 67(2):562-7. PMC: 96355. DOI: 10.1128/IAI.67.2.562-567.1999. View

15.

Rhie G, Roehrl M, Mourez M, Collier R, Mekalanos J, Wang J . A dually active anthrax vaccine that confers protection against both bacilli and toxins. Proc Natl Acad Sci U S A. 2003; 100(19):10925-30. PMC: 196904. DOI: 10.1073/pnas.1834478100. View

16.

Little S, Ivins B, Fellows P, Pitt M, Norris S, Andrews G . Defining a serological correlate of protection in rabbits for a recombinant anthrax vaccine. Vaccine. 2003; 22(3-4):422-30. DOI: 10.1016/j.vaccine.2003.07.004. View

17.

Reuveny S, White M, Adar Y, Kafri Y, Altboum Z, Gozes Y . Search for correlates of protective immunity conferred by anthrax vaccine. Infect Immun. 2001; 69(5):2888-93. PMC: 98239. DOI: 10.1128/IAI.69.5.2888-2893.2001. View

18.

Baillie L . The development of new vaccines against Bacillus anthracis. J Appl Microbiol. 2001; 91(4):609-13. DOI: 10.1046/j.1365-2672.2001.01498.x. View

19.

JERNIGAN J, Stephens D, Ashford D, Omenaca C, Topiel M, Galbraith M . Bioterrorism-related inhalational anthrax: the first 10 cases reported in the United States. Emerg Infect Dis. 2001; 7(6):933-44. PMC: 2631903. DOI: 10.3201/eid0706.010604. View

20.

Liu S, Leppla S . Cell surface tumor endothelium marker 8 cytoplasmic tail-independent anthrax toxin binding, proteolytic processing, oligomer formation, and internalization. J Biol Chem. 2002; 278(7):5227-34. DOI: 10.1074/jbc.M210321200. View