Toxin-neutralizing antibodies elicited by naturally acquired cutaneous

Abstract

Understanding immune responses to native antigens in response to natural infections can lead to improved approaches to vaccination. This study sought to characterize the humoral immune response to anthrax toxin components, capsule and spore antigens in individuals (n = 46) from the Kayseri and Malatya regions of Turkey who had recovered from mild or severe forms of cutaneous anthrax infection, compared to regional healthy controls (n = 20). IgG antibodies to each toxin component, the poly-gamma- D-glutamic acid capsule, the Bacillus collagen-like protein of anthracis (BclA) spore antigen, and the spore carbohydrate anthrose, were detected in the cases, with anthrax toxin neutralization and responses to Protective Antigen (PA) and Lethal Factor (LF) being higher following severe forms of the disease. Significant correlative relationships among responses to PA, LF, Edema Factor (EF) and capsule were observed among the cases. Though some regional control sera exhibited binding to a subset of the tested antigens, these samples did not neutralize anthrax toxins and lacked correlative relationships among antigen binding specificities observed in the cases. Comparison of serum binding to overlapping decapeptides covering the entire length of PA, LF and EF proteins in 26 cases compared to 8 regional controls revealed that anthrax toxin-neutralizing antibody responses elicited following natural cutaneous anthrax infection are directed to conformational epitopes. These studies support the concept of vaccination approaches that preserve conformational epitopes.

C1 [Dumas, Eric K.; Sparks, Rebecca M.; Muns, Emily; Zamora, Adriana; Garman, Lori; James, Judith A.; Farris, A. Darise] Oklahoma Med Res Fdn, Arthrit & Clin Immunol Program, 825 NE 13th St, Oklahoma City, OK 73104 USA.

[Dumas, Eric K.; Larabee, Jason; Garman, Lori; Ballard, Jimmy D.; Farris, A. Darise] Univ Oklahoma, Hlth Sci Ctr, Dept Microbiol & Immunol, Oklahoma City, OK 73190 USA.

[Demiraslan, Hayati; Doganay, Mehmet] Erciyes Univ, Fac Med, Dept Infect Dis, Kayseri, Turkey.

[Ingram, Rebecca J.] Queens Univ Belfast, Ctr Infect & Immun, Belfast, Antrim, North Ireland.

[Boons, Geert-Jan] Univ Georgia, Complex Carbohydrate Res Ctr, 220 Riverbend Rd, Athens, GA 30602 USA.

[Boons, Geert-Jan] Univ Georgia, Dept Chem, Athens, GA 30602 USA.

[Boons, Geert-Jan] Univ Utrecht, Utrecht Inst Pharmaceut Sci, Dept Chem Biol & Drug Discovery, Utrecht, Netherlands.

[Boons, Geert-Jan] Univ Utrecht, Bijvoet Ctr Biomol Res, Utrecht, Netherlands.

[James, Judith A.] Univ Oklahoma, Hlth Sci Ctr, Dept Med, Oklahoma City, OK USA.

[James, Judith A.] Univ Oklahoma, Hlth Sci Ctr, Dept Pathol, Oklahoma City, OK USA.

[Kayabas, Uner] Inonu Univ, Fac Med, Dept Infect Dis & Clin Microbiol, Malatya, Turkey.

[Kayabas, Uner] Istanbul Arel Univ, Fac Med, Dept Infect Dis & Clin Microbiol, Istanbul, Turkey.