Anti-Idiotypic Nanobodies Mimicking an Epitope of the Needle Protein of the Chlamydial Type III Secretion System for Targeted Immune Stimulation

Int J Mol Sci. 2024 Feb 7;25(4):2047. doi: 10.3390/ijms25042047.

Abstract

The development of new approaches and drugs for effective control of the chronic and complicated forms of urogenital chlamydia caused by Chlamydia trachomatis, which is suspected to be one of the main causes of infertility in both women and men, is an urgent task. We used the technology of single-domain antibody (nanobody) generation both for the production of targeting anti-chlamydia molecules and for the subsequent acquisition of anti-idiotypic nanobodies (ai-Nbs) mimicking the structure of a given epitope of the pathogen (the epitope of the Chlamydial Type III Secretion System Needle Protein). In a mouse model, we have shown that the obtained ai-Nbs are able to induce a narrowly specific humoral immune response in the host, leading to the generation of intrinsic anti-Chlamydia antibodies, potentially therapeutic, specifically recognizing a given antigenic epitope of Chlamydia. The immune sera derived from mice immunized with ai-Nbs are able to suppress chlamydial infection in vitro. We hypothesize that the proposed method of the creation and use of ai-Nbs, which mimic and present to the host immune system exactly the desired region of the antigen, create a fundamentally new universal approach to generating molecular structures as a part of specific vaccine for the targeted induction of immune response, especially useful in cases where it is difficult to prepare an antigen preserving the desired epitope in its native conformation.

Keywords: Chlamydia; anti-idiotypic antibodies; biomimetic; immunomodulation; nanobody; single-domain antibody; urogenital infection.

MeSH terms

  • Animals
  • Antibodies, Bacterial
  • Chlamydia Infections*
  • Chlamydia trachomatis
  • Epitopes
  • Female
  • Humans
  • Mice
  • Single-Domain Antibodies*
  • Type III Secretion Systems

Substances

  • Epitopes
  • Single-Domain Antibodies
  • Type III Secretion Systems
  • Antibodies, Bacterial