Elsevier

Clinica Chimica Acta

Volume 507, August 2020, Pages 117-124
Clinica Chimica Acta

Review
Research status and perspectives for pathogenic spirochete vaccines

https://doi.org/10.1016/j.cca.2020.04.002Get rights and content

Highlights

  • The global prevalence and incidence of spirochetosis diseases remain high.

  • This review highlights research progress into a pathogenic spirochete vaccine.

  • Gene-editing methods will likely promote the development of relevant vaccines.

  • Present an overview of the current state of the field for spirochete vaccine development.

  • Pointing out major challenges and areas that require further investigation.

  • Critically summarizes the most recent advances in the field.

Abstract

Leptospira interrogans, Borrelia burgdorferi, and Treponema pallidum are important pathogenic spirochetes. The incidence of human diseases caused by pathogenic spirochetes, e.g., leptospirosis, Lyme disease, and syphilis, has been recently increased, posing a threat to public health. Mechanisms of spirochete pathogenicity are not yet fully understood, and no safe and effective vaccine to prevent and control the infection by pathogenic spirochetes is currently available. In this article, we review the progress of research into the pathogenic spirochete vaccine, mainly in terms of vaccine types. The development of relevant vaccines against pathogenic spirochetes has generally proceeded via several stages, such as the whole-cell inactivated vaccine, live attenuated vaccine, and gene-engineered vaccine, and will likely enter a new stage with the application of gene editing technology.

In this review, we mainly summarized the types of pathogenic spirochete vaccines and conducted a preliminary analysis on the protective effect of immunity, and proposed a further prospect for the development of pathogenic spirochete vaccines.

Introduction

Spirochetes (also spelled spirochaetes) are a group of long, slender, curved, spiral-shaped prokaryotes that exist widely in nature. Some spirochetes are important human pathogens. Pathogenic spirochetes belong to three genera: Leptospira, Borrelia, and Treponema, represented, respectively, by Leptospira interrogans (L. interrogans), which causes leptospirosis; Borrelia burgdorferi (B. burgdorferi), which causes Lyme disease; and Treponema pallidum (T. pallidum), which causes syphilis. Serological detection of spirochete infection is important for clinical diagnosis, and antibiotic use can achieve a good therapeutic effect. Nevertheless, human diseases caused by pathogenic spirochetes cannot be effectively controlled at present and their incidence rates remain high. Such as, worldwide more than 1 million new cases of leptospirosis are diagnosed every year [1], more than 1 million cases of Lyme disease per year [2], and 5 million cases of syphilis patients occur each year [3].The incidence of spirochetosis is still on the rise and constituting a public health problem that urgently needs to be solved.

Currently, vaccination is an effective and economical method for controlling pathogen infection. However, anti-spirochete vaccines have some limitations. For instance, triggering off a strong anaphylactic reaction, excessive immunization time and high dosage, high serotype diversity in different regions, have curtailed the extensive use of a whole-cell inactivated vaccine against leptospirosis. Further, because of potential side effects and a small number of vaccinations, Lyme disease vaccines that had reached the market were soon removed [4]. By contrast, no vaccines that could be used directly in the clinic are currently available for syphilis, although the incidence of this disease is high. Accordingly, currently, the development of an advanced pathogenic spirochete vaccine is an important research topic.

In the current review, we introduce and summarize the research status of each type of pathogenic spirochetes vaccine.

Section snippets

Whole-cell inactivated vaccines

A whole-cell inactivated vaccine, a type of biological preparation, contains a pathogenic organism that had been killed by physical or chemical methods, but retains antigenicity. In China, a leptospirosis vaccine was successfully developed by researchers who inactivated Leptospira with formalin, in 1950s. The occurrence of hypersensitivity reactions and cross-reaction was dramatically reduced after optimization of the Leptospira culture medium composition and the development of a multivalent

Live attenuated vaccines

Live attenuated vaccine, a type of vaccine that contains an attenuated pathogenic organism, can elicit an immune protective response without causing obvious disease symptoms. Just a few doses of live attenuated vaccine can induce systemic and mucosal immune protection. Compared with the whole-cell inactivated vaccine, the live attenuated vaccine is characterized by high immunogenicity, long immunity duration, and other advantages. However, this type of vaccine may be associated with a potential

Genetically-engineered vaccines

Genetically-engineered vaccine refers to a vaccine generated using expressed antigenic constructs or recombinants by transferring the protective antigen genes to a eukaryotic or prokaryotic expression vector. In addition to the advantages of strong immunogenicity and convenient production, safety issues of vaccine-associated infection caused by incomplete inactivation and virulence of attenuated strains are reduced for genetically engineered vaccines. These vaccines are typically classified

Multi-epitope vaccines

The multi-epitope vaccine is a new type of a molecular vaccine that simultaneously encodes multiple target antigens and auxiliary antigens.

Because leptospira has 15 serovar/serogroup in China, so Lin Xuai et al. designed a chimera epitope vaccines (named r4R) for cross-protection. The vaccine containing six T- and B-cell epitopes,which encoded by genes for leptospiral OMPs OmpL1, LipL32, and LipL21. The r4R vaccine induced the Th1-biased immune response in guinea pig [56]. Furthermore, no

Overview of the development of pathogenic spirochete vaccines

In the search for vaccines against leptospirosis, the priority has long been given to whole-cell vaccines. However, high risk of eliciting hypersensitivity, poor specificity, and short-lasting protection have prevented wide use of Leptospira vaccines. OMPs are the most valuable antigenic proteins for vaccine development. However, OMPs such as LigA, LipL41, and OmpL1, elicit only partial protection against Leptospira infection. Further, the scarce number and abundance of OMPs in the Tp outer

Summary and perspectives

The current vaccine research is focusing on several aspects of vaccine development, including different types of vaccines, optimization of immunization strategies, and selection of novel adjuvants and vectors. However, in practice, no effective, practical, and safe vaccine for pathogenic spirochetes is currently available. The future research into pathogenic spirochete vaccines could be expanded to include the following:

  • (1)

    In combination with bioinformatics analysis (e.g., RV) and characterization

Author contributions

Junxia Duan and Yue Zhao wrote the manuscript; Xiaohong Zhang and Tie Zhao designed and arranged the tables; Han Jiang and Bibo Xie collected the data; Feijun Zhao modified and organized the manuscript.

Funding

This work was supported by the National Natural Science Foundation of China (no. 81971980); Hunan Provincial Education Department Key Project (no. 18A242); and Hunan Province College Students’ Research, Learning, and Innovative Experiment Project (no. S201910555124).

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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