Past, present, and future of Lyme disease vaccines: antigen engineering approaches and mechanistic insights

ABSTRACT

Introduction

Transmitted by ticks, Lyme disease is the most common vector-borne disease in the Northern hemisphere. Despite the geographical expansion of human Lyme disease cases, no effective preventive strategies are currently available. Developing an efficacious and safe vaccine is therefore urgently needed. Efforts have previously been taken to identify vaccine targets in the causative pathogen (Borrelia burgdorferi sensu lato) and arthropod vector (Ixodes spp.). However, progress was impeded due to a lack of consumer confidence caused by the myth of undesired off-target responses, low immune responses, a limited breadth of immune reactivity, as well as by the complexities of the vaccine process development.

Area covered

In this review, we summarize the antigen engineering approaches that have been applied to overcome those challenges and the underlying mechanisms that can be exploited to improve both safety and efficacy of future Lyme disease vaccines.

Expert opinion

Over the past two decades, several new genetically redesigned Lyme disease vaccine candidates have shown success in both preclinical and clinical settings and built a solid foundation for further development. These studies have greatly informed the protective mechanisms of reducing Lyme disease burdens and ending the endemic of this disease.

KEYWORDS:

• Antigen design
• Borrelia
• genetic engineering
• Lyme borreliae

Article highlights

• Lyme disease, caused by the pathogen Borrelia burgdorferi sensu lato, is the most common vector-borne disease in the Northern hemisphere, yet no effective preventive strategies are currently available.

• Vaccine candidates originating in the pathogen (Borrelia burgdorferi sensu lato) and in the vector (Ixodes spp.) have been evaluated; however, several challenges, such as low consumer confidence caused by the myth of off-target responses, a limited breadth of immune reactivity, low-level immune responses and complexities within the vaccine process development, have impacted progress.

• Antigen engineering was shown to not only improve the immune response targeting the desired immunologically subdominant epitopes but also prevent the production of off-target antibodies.

• Antigen editing was shown to simplify the production process and improve the stability of vaccine candidates.

Acknowledgments

We thank Klemen Strle for critical reading and editing the manuscript.

Disclosure statement

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

This work was supported by NIH R21AI144891, DoD TB190048.