The question of the link between vaccinations and Lyme disease has arisen with increasing frequency in recent years, both in clinical practice and based on patients’ experiences; however, the scientific literature currently remains limited and relies partly on indirect evidence. However, based on the available data, several mechanisms can be outlined that may explain why atypical immune responses or adverse reactions following vaccination may develop in patients with Lyme disease or chronic Lyme symptoms.
Disruption of the immune response
The issue of immunological responsiveness is of fundamental importance. The Borrelia burgdorferi complex, which causes Lyme disease, has an immunomodulatory effect capable of influencing both the innate and adaptive immune responses. The immune response that develops during infection is often suboptimal, partly due to the pathogen’s immune evasion mechanisms. This phenomenon may explain why, in some cases, the infected host is unable to develop effective, long-lasting immune memory. The mechanism of action of vaccines is based precisely on this formation of immune memory; thus, it is theoretically conceivable that in a host already in an immunologically dysregulated state, the response to vaccination will be reduced or atypical. Although direct human studies on the vaccination response in Lyme disease patients are scarce, studies conducted in other immunocompromised populations provide important indirect insights.
Theoretical considerations regarding the reduced efficacy of the immune response have been supported in recent years by clinical trials related to COVID-19 vaccination, even if these were not specifically conducted on patients with Lyme disease. Several studies conducted in immunocompromised populations – including organ transplant recipients and patients receiving immunomodulatory treatment – have clearly demonstrated that the immune response following vaccination may be significantly reduced, and in some cases, immunity may not develop at all.
Studies conducted on organ transplant recipients (e.g. heart and lung transplant recipients) found that, following mRNA-based COVID-19 vaccines, a significant proportion of patients did not develop an adequate antibody response, or only a low level of antibodies was detectable. In some groups, the seroconversion rate was particularly low and did not reach the levels observed in the healthy population even after repeated vaccinations (booster doses). Similar observations have been made in multiple sclerosis and other autoimmune diseases, particularly in conjunction with certain immunotherapies, where the B-cell response was markedly suppressed. These studies show that the functional state of the immune system has a decisive influence on whether a vaccine is capable of conferring effective protection.
These findings are particularly relevant in the context of Lyme disease. Although direct clinical studies on the COVID-19 vaccination response in Lyme disease patients are currently limited in number, the immunological changes induced by Borrelia infection show similarities in several respects to conditions in which a reduction in vaccine efficacy has already been demonstrated. Borrelia burgdorferi is known to disrupt the B-cell immune response, impair the function of germinal centres, and influence the development of memory cells. This process directly affects the mechanism through which the protective effect of vaccines is established.
The immune response generated by vaccines in patients with Lyme disease
Animal models have shown that, in the presence of Borrelia infection, the immune response to other antigens may also be impaired, suggesting that the infection may induce not only a specific but also a general immune response disorder. In light of this, it may be biologically plausible to assume that, in the case of Lyme disease caused by Borrelia bacterial infection, vaccination against any infectious agent – including others – does not always lead to the development of adequate immunity. This does not necessarily mean that the vaccine is ineffective, but rather that the resulting immune response is weaker, of shorter duration, or functionally inadequate.
Clinical data on COVID-19 vaccines further reinforce this interpretation: several studies have observed that, even after repeated vaccinations, an adequate neutralising antibody response does not develop in certain patients, which may indeed result in reduced clinical protection. This phenomenon is particularly significant when the immune system is already compromised. The chronic immune activation and dysregulation associated with Lyme disease could potentially create a similar situation in this respect.
Based on all this, the possibility is becoming increasingly apparent that in some patients with Lyme disease, full protective immunity does not develop following vaccination. This may stem from deficiencies in the immune response rather than from the inadequacy of the vaccine. The phenomenon may be particularly pronounced in cases where persistent immune system abnormalities remain as a result of the infection.
It is important to emphasise, however, that this conclusion is currently based mainly on indirect evidence. Targeted, controlled human trials are required to accurately map the relationship between Lyme disease and vaccination. Nevertheless, based on a combined interpretation of the available immunological and clinical data, it cannot be ruled out that, in certain Lyme disease patients, vaccine-induced immunity does not develop to an adequate extent.
Research into the development of Lyme vaccines also highlights that the development of immunity is dose-dependent and not always complete, reflecting the complexity of the immune response. Furthermore, general immunological models describe how, in the case of certain infections, the immune system can enter a ‘dysregulated’ state, which influences the response to subsequent antigens.
Adverse events considered “anecdotal”
Another important aspect is the effect of adjuvants found in vaccines. The purpose of adjuvants is to enhance the immune response; however, this effect is not always specific and may trigger excessive reactions, particularly in a highly sensitive or already activated immune system. Numerous studies confirm that during immune activation, various mediators, including histamine and inflammatory cytokines, are released, contributing to post-vaccination reactions. From a neuroimmune perspective, it is particularly relevant that mast cells – which play a key role in histamine release – can be activated not only via classical allergic mechanisms but also in response to immune and neural stimuli. This is consistent with observations that certain individuals may experience heightened autonomic, neurological or inflammatory symptoms following vaccination.
In the case of Lyme disease, this mechanism may be particularly significant. The chronic immune activation and neuroinflammation associated with the infection may create a ‘primarily sensitised’ state in which the immune system exhibits heightened responsiveness. In this context, adjuvant-induced immune activation may not only induce a protective immune response but also the release of undesirable mediators, including histamine and other inflammatory factors. Although this phenomenon is not specific to Lyme disease but can be interpreted as a general immunological reaction, symptoms may be more severe or prolonged due to an existing infection or post-infectious condition.
It is important to emphasise that current scientific evidence does not unequivocally support the claim that vaccinations ‘activate’ or exacerbate Lyme disease in an infectious biology sense. At the same time, patient reports and certain observations suggest that a temporary worsening of symptoms may occur in certain cases. The scientific discourse on Lyme disease increasingly reflects the view that persistent symptoms are not necessarily driven solely by the active infection itself, but by immune-mediated and neuroimmune processes. Within this interpretative framework, the immune activation triggered by vaccinations may potentially be capable of modulating these processes, either in a beneficial or an adverse direction.
The interpretation of vaccination reactions observed among Lyme disease patients is further complicated by the fact that the available data are largely indirect or anecdotal in nature. Reports frequently appear in patient communities and forums stating that symptoms have worsened following a vaccination, but these observations do not replace controlled clinical trials. According to the current state of the scientific literature, there is insufficient, well-controlled data to suggest that the immune response of patients with Lyme disease differs significantly from that of the healthy population following vaccination; however, based on general knowledge regarding immune system dysregulation, this possibility cannot be ruled out and, indeed, is plausible.
Overall, it can be said that the effect of vaccinations in patients with Lyme disease is complex and may vary from person to person. Based on theoretical and, in part, experimental data, it can be assumed that, on the one hand, the immune response is not always optimal, and on the other hand, the immune activation triggered by adjuvants – particularly in an already dysregulated neuroimmune environment – may induce undesirable reactions, for example through histamine release. However, it must be emphasised that these mechanisms have not yet been fully demonstrated in a specific population of Lyme disease patients, and further targeted clinical research is required to clarify the issue.
Sources:
https://pubmed.ncbi.nlm.nih.gov/34409119/
https://pmc.ncbi.nlm.nih.gov/articles/PMC8364756/
https://pmc.ncbi.nlm.nih.gov/articles/PMC4964673/
https://pmc.ncbi.nlm.nih.gov/articles/PMC9529901/
https://pmc.ncbi.nlm.nih.gov/articles/PMC7155782/
https://pubmed.ncbi.nlm.nih.gov/40353219/
https://www.niaid.nih.gov/diseases-conditions/lyme-disease-vaccines
https://arxiv.org/abs/2504.08777
(C) Lyme Borreliosis Foundation
