Toxin-neutralizing antibodies elicited by naturally acquired cutaneous anthrax are elevated following severe disease and appear to target conformational epitopes

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-γ-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.

Human anthrax in Turkey: A ten years’ experience (2009–2018)

“…Anthrax is primarily a disease of herbivores; human beings can be incidentally infected, almost invariably directly or indirectly from animals or animal products. 1–3…”

“…Anthrax is primarily a disease of herbivores; human beings can be incidentally infected, almost invariably directly or indirectly from animals or animal products. [1][2][3] The vast majority of human cases of anthrax occurs as a consequence of environmental exposure and, as such, is readily controllable. 4 B. anthracis can infect humans by cutaneous, gastrointestinal, or respiratory routes.…”

Gambaran Umum, Prevalensi, dan Pencegahan Antraks pada Manusia di Indonesia

“…Antraks pada manusia dapat dibagi menjadi beberapa bentuk berdasarkan gejala klinis dan rute transmisinya yaitu antraks kulit (kutaneus), antraks tipe saluran pencernaan (gastrointestinal), antraks paru-paru (pulmonar/ inhalasi), dan antraks injeksi. 19,35 Setiap bentuk antraks memiliki potensi untuk berkembang menjadi infeksi sistemik yang fatal seperti sepsis dan meningitis sebagai akibat dari penyebaran limfohematogen B. antrachis dari lesi primer antraks kutaneus, gastrointestinal, maupun inhalasi. 14 Sebagian besar kasus antraks pada manusia merupakan antraks kutaneus (95%) dan jarang berakibat fatal dengan pengobatan antibiotik.…”

“…3,34 Edema Toxin (EdTx) dan Lethal Toxin (LeTx) yang dihasilkan B. anthrachis dapat merusak sistem kekebalan tubuh bawaan maupun adaptif. 35 Toksin B. antrachis dapat masuk ke dalam sitoplasma beberapa jenis sel termasuk sel imun, EdTx akan meningkatkan cyclic AMP (cAMP) intrasel yang menyebabkan gangguan homeostasis air dan edema. 15 Edema Toxin juga dapat menghambat aktivitas makrofag dengan memodifikasi produksi sitokin yang menyebabkan penurunan sirkulasi limfosit dan penurunan fungsi neutrofil.…”

“…14 Lethal Toxin akan memotong N-terminal dari enzim mitogenactivated kinase kinases (MAPKKs atau MEKs) dan mengganggu jalur sinyal yang penting dalam regulasi sel, proliferasi, dan pertahanan stres seluler. 15,35 Selain itu, LeTx juga dapat mengganggu atau mematikan produksi dan fungsi makrofag, sel dendritik, neutrofil, beberapa epitel, dan sel endotelial serta menurunkan regulasi produksi sitokin, menghambat induksi kemokin antimikrobia, menghambat proliferasi sel B, dan produksi imunoglobulin. 14 Tingkat keparahan infeksi antraks tergantung dari jumlah bakteri yang menginfeksi, tingkat virulensi bakteri, kondisi imunitas bawaan (innate) dan imunitas spesifik individu.…”