Immunization with the N-Terminal Portion ofTreponema pallidumRepeat Protein K Attenuates Syphilitic Lesion Development in the Rabbit Model

Abstract

When used as an immunogen, Treponema pallidum repeat protein K (TprK) has been shown to attenuate syphilitic lesions upon homologous intradermal challenge in the rabbit model. To further explore this protein as a potential vaccine component, we sought to identify the immunogenic regions of TprK. The abilities of three recombinant peptides encompassing TprK to elicit T-and B-cell responses and to protect against challenge were examined. All three fragments elicited proliferative responses from splenocytes taken from infected rabbits. However, enzyme-linked immunosorbent assays indicated that only fragments 1 and 3 were consistently recognized by antisera from infected rabbits. Each fragment was also used to immunize rabbits that were subsequently challenged intradermally with infectious T. pallidum. All lesions on unimmunized control rabbits ulcerated and contained treponemes, while the lesions on rabbits immunized with fragment 1 were the least likely to have detectable treponemes (25%) and the least likely to ulcerate (37.5%). The lesions on rabbits immunized with fragment 3 showed intermediate results, and rabbits immunized with fragment 2 were the most likely of all those on immunized rabbits to have detectable treponemes (91.7%) and to ulcerate (66.7%). These results demonstrate that epitopes in fragment 1 are recognized by T cells and antibodies during infection and that immunization with this portion of TprK most effectively attenuates syphilitic lesion development.

Syphilis: using modern approaches to understand an old disease

“…This protocol was very cumbersome and expensive, and impractical to test in humans. Immunization with recombinant T. pallidum antigens can stimulate production of an immune response in the rabbit model, resulting in only partial protection, with significantly attenuated lesion development but no sterile immunity (80,83,(142)(143)(144)(145). The discovery of antigenic variation in TprK makes the development of a protective vaccine even more formidable.…”

“…Among Tpr family members, TprK is the best studied. A strong antibody and T cell immune response is elicited against TprK (81,82), and immunization with recombinant TprK provides partial immunity against infectious challenge (80,83). Antibodies raised against recombinant TprK can opsonize T. pallidum for phagocytosis by macrophages in vitro (80).…”

Quantitative Analysis oftprGene Expression inTreponema pallidumIsolates: Differences among Isolates and Correlation with T-Cell Responsiveness in Experimental Syphilis

“…Although major T-cell antigens include T. pallidum lipoproteins and endoflagellar polypeptides, TprK, TprI, and the amino-terminal conserved subfamily I peptide were also shown to be strong targets for the cellular component of the immune response (17,19,22), emphasizing again the importance of these antigens in the immune response to syphilis infection.…”

“…Although the function of the Tprs is still unknown and attempts to determine the cellular location of TprI and TprK have resulted in controversial results (10,12), several studies have highlighted the importance of these antigens during the immune response to syphilis in the rabbit model (17,19,22). Immunization with recombinant peptides based on TprI, TprF, and TprK sequences significantly alters lesion development after intradermal challenge (3,10,22); moreover, TprK possesses multiple alleles in T. pallidum isolates, conferring an impressive potential for antigenic variation and, consequently, of immune evasion (4,5).…”

“…pallidum (referred to here as simply T. pallidum), Nichols strain (8). Subsequently, interest in the tpr genes has continued to rise in parallel to the corpus of data relative to these potential virulence factors (4,5,13,(17)(18)(19)22). The predicted Tpr antigens can be divided into three subfamilies, based upon predicted amino acid sequence homology: subfamily I (TprC, -D, -F, and -I), subfamily II (TprE, -G, and -J), and subfamily III (TprA, -B, -H, -K, and -L).…”