Lyme disease: towards the return of a vaccine?

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


Lyme disease is the most common vector-borne disease in North America and Europe, caused by the bacterium Borrelia burgdorferi. Its incidence continues to rise, making it a major public health concern. However, no vaccine is currently available for humans since the withdrawal of LYMErix in 2002 due to safety concerns and insufficient uptake.

The disease presents significant clinical variability, ranging from early flu-like symptoms to late complications affecting the joints, nervous system, or heart. This diversity, combined with a complex transmission cycle involving ticks and animal hosts, makes prevention particularly challenging.

In this context, the development of an effective, safe, and durable vaccine represents a major challenge. This systematic review and meta-analysis, recently published in Frontiers in Cellular and Infection Microbiology, aims to evaluate the most promising vaccine candidates currently under development in order to identify the most relevant strategies for future human vaccination.

What vaccines for lyme disease ?

The study is based on a rigorous analysis of 16 studies selected from more than 300 publications. The data mainly come from preclinical trials conducted in animals, particularly mice and hamsters, allowing assessment of vaccine efficacy and safety.

The results show that most vaccine strategies are based on the Borrelia surface protein OspA, already used in the LYMErix vaccine. However, new approaches aim to improve its profile by combining this protein with other technologies, such as nanoparticles, membrane vesicles, or mRNA platforms.

Some innovative strategies involve fusing different variants of OspA to target multiple Borrelia species, or incorporating the antigen into structures that mimic the bacterium to enhance the immune response. Other candidates target alternative proteins, such as VlsE, P66, or BB0172, with variable but sometimes promising results.

Data indicate that several candidates—particularly OspA-based formulations, multivalent vaccines, or those combined with membrane vesicles—induce a significant protective immune response in animal models. Notably, modified OspA vaccines appear to be the most effective, while aiming to reduce the adverse effects observed with earlier generations.

What challenges for an effective vaccine ?

The development of a Lyme disease vaccine faces several challenges. The diversity of Borrelia species, variability in immune responses, and the complexity of the transmission cycle complicate the design of a universal vaccine.

Animal models, while essential, also have limitations. For example, some models do not accurately reproduce human complications, particularly Lyme arthritis, making safety evaluation more difficult. The introduction of more relevant models, such as C3H mice, has improved assessment, but uncertainties remain.

Additionally, the heterogeneity of studies in terms of formulations, doses, and protocols makes comparisons difficult and highlights the need for standardization in future trials.

Towards a new generation vaccine ?

This meta-analysis highlights the potential of several vaccine candidates, particularly those based on OspA and its derivatives, which remain the most advanced and promising. New technologies, such as mRNA vaccines or nanoparticles, open up interesting perspectives for improving the effectiveness and durability of the immune response.

However, despite encouraging preclinical results, several steps remain before clinical application. It is necessary to confirm long-term efficacy, assess safety in humans, and better understand the underlying immune mechanisms.

“The development of a vaccine against Lyme disease now relies on a combination of technological innovations and a better understanding of the immune response,” the authors suggest.

Ultimately, these advances could help fill a major public health gap and significantly reduce the incidence of Lyme disease—provided these strategies are validated in rigorous clinical trials.



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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 through impactful communication.