Lyme disease: is the vaccine making a comeback?

By Ana Espino | Published on May 7, 2026 | 4 min read


Lyme disease is currently the most common vector-borne disease in temperate regions, particularly in North America and Europe. It is caused by the bacterium Borrelia burgdorferi, transmitted to humans through ticks of the Ixodes genus. Its incidence continues to rise, making it a significant public health concern.  

Clinically, the disease initially presents with often mild symptoms, such as erythema migrans or flu-like signs, but it can progress to more severe forms affecting the joints, nervous system, or heart. Despite this growing burden, no human vaccine has been available since the withdrawal of LYMErix in 2002, mainly due to safety concerns and low public acceptance. This situation highlights the urgent need to develop new, effective, and safe vaccination strategies.

What vaccine for the future?

The objective of this study, recently published in Applied Microbiology and Biotechnology, is to provide a comprehensive overview of vaccines currently under development for Lyme disease. The authors aim to compare their efficacy, safety, and ability to induce a durable immune response. This approach helps identify the most promising candidates and better guide future research in a field where data have so far remained fragmented.

Which candidates are in the race ? 

The authors conducted a systematic review and meta-analysis following PRISMA guidelines, with a rigorous selection of 16 studies from multiple databases. The data are mainly based on animal models, particularly mice and hamsters. Some models, such as BALB/c mice, allow detailed study of immune responses, while others, like C3H/HeN mice, are better suited to reproducing certain human manifestations, notably Lyme arthritis.  

Statistical analyses were performed using random-effects models, with assessment of heterogeneity between studies and correlations between infection rates and levels of protection.  

The vaccine candidates studied rely on various approaches. Most target the surface protein OspA, previously used, but with improvements aimed at optimizing efficacy and safety. Other strategies explore alternative proteins such as P66 or VlsE, as well as specific peptides like BB0172. More innovative approaches involve nanoparticles, membrane vesicles, and mRNA-based platforms.

 Which protects best ?

The results show that several candidates, particularly those based on OspA or its derivatives, induce significant protection in animal models. Formulations combining OspA with membrane vesicles or using multivalent forms appear especially effective. Some recombinant proteins, such as P66 and VlsE, as well as the BB0172 peptide, also show encouraging results. However, not all candidates demonstrate the same level of efficacy, highlighting the importance of antigen selection and formulation. Overall, vaccination is associated with a significant reduction in infection rates and improved protection in the studied animals.

A turning point for Lyme prevention?

This study highlights the potential of several vaccine candidates, particularly those based on OspA and recombinant proteins. New technologies, such as mRNA vaccines and nanoparticles, also offer promising prospects for improving both the efficacy and durability of the immune response. Nanoparticles, especially those based on ferritin, allow better antigen presentation and a more robust immune response, while membrane vesicles, by mimicking bacterial structure, promote a more effective response.  

However, these results still need to be confirmed in humans. Future research will need to focus on optimizing formulations, while safety remains a central concern. Finally, the lack of data from human clinical trials represents a major obstacle to validating these vaccine candidates.  

In the long term, the development of an effective vaccine against Lyme disease could represent a major public health breakthrough, significantly reducing the incidence of this steadily increasing disease.  



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About the author – Ana Espino
PhD in Immunology, specialized in Virology  
As a scientific writer, Ana is passionate about bridging the gap between research and real-world impact. With expertise in immunology, virology, oncology, and clinical studies, she makes complex science clear and accessible. Her mission: to accelerate knowledge sharing and empower evidence-based decisions