Strategies for syphilis vaccine development

Abstract

Research to identify a syphilis vaccine began shortly after the isolation of the first Treponema pallidum subspecies pallidum (T. pallidum) strain in 1912 by Nichols and Hough and the identification of several possible animal models for the infection, with the rabbit being the best one. During the century following T. pallidum isolation, none of the numerous immunization/challenge experiments performed with preparations ranging from whole-inactivated T. pallidum cells to recombinant proteins yielded an effective vaccine, and the search for a vaccine languished. Recently, however, scientific communities have experienced a resurgence in interest in developing a syphilis vaccine due to 1. the awareness that syphilis constitutes a tremendous burden for maternal health, particularly in low- and middle-income nations; 2. the improved understanding of the immunological processes leading to pathogen clearance during natural infection and of the mechanisms this pathogen developed to persist in the host; 3. the availability of a near-complete list of T. pallidum genes encoding putative surface-exposed antigens, which represent the most likely vaccine candidates; and, last but not least, 4. the effort made to expand the knowledge on the genetic and antigenic diversity of these vaccine candidates in strains circulating worldwide. Thus far, the most recent vaccine designs based on a subset of the pathogen’s surface-exposed antigens have provided immunized rabbits with a significant but incomplete protection upon infectious challenge. Nonetheless, the outcomes of these experiments help investigators refine strategies to achieve a formulation with the highest chances of moving from preclinical experimental settings to clinical trials. This editorial focuses on a subset of the strategies currently believed to be essential for vaccine development, namely, the improvement of our still limited understanding of the genomic diversity in T. pallidum strains from diverse geographical locations through the collection and isolation of modern syphilis strains and the identification of protective epitopes in potential vaccine targets by evaluating the ability of monoclonal antibodies to bind the target antigen and facilitate pathogen clearance. The use of genetic engineering of the syphilis spirochete to identify target surface proteins with an essential or near-essential role in T. pallidum biology to target in immunization/challenge experiments is also discussed.

Advancing Syphilis Research: Exploring New Frontiers in Immunology and Pharmacological Interventions

“…Moreover, the integration of multiple tests into a single platform, enabling simultaneous detection of different sexually transmitted infections, including syphilis, is being pursued. Multiplexed assays have the potential to enhance the efficiency of screening programs, reducing the burden on healthcare facilities and allowing for comprehensive testing in one simple procedure [94,95].…”

Advancing Syphilis Research: Exploring New Frontiers in Immunology and Pharmacological Interventions

“…As the target population for a syphilis vaccine may differ from that of other STI vaccines, considerations must be given to factors such as age, gender, and risk behaviors. Determining the optimal age for vaccination, identifying high-risk groups, and tailoring the vaccine to address specific transmission patterns are critical aspects of designing an effective vaccination strategy [51,53].…”