Tick-borne encephalitis virus vaccination breakthrough infections in Germany: a retrospective analysis from 2001 to 2018

Abstract

Objectives: There are few data available regarding the clinical course of tick-borne encephalitis virus (TBEV) vaccination breakthrough infections. The published studies suggest that vaccination breakthrough infections may have a more severe course than native TBEV infection in unvaccinated individualsdpotentially due to antibody-dependent enhancement. Here we report a large analysis of vaccination breakthrough infections. Methods: This retrospective analysis was based on a national surveillance dataset spanning the years 2001e2018. Variables reflecting disease severity, such as 'CNS symptoms', 'myelitis', 'fatal outcome' and 'hospitalization' were analysed as well as general epidemiological variables. Cases were categorized as 'unvaccinated' or 'ever vaccinated', the latter category including cases with at least one dose of a TBEV vaccine. Results: A total of 6073 notified TBEV infection cases were included in our analysis. Sufficient data on vaccination status were available for 95.1% of patients (5777/6073); of these, 5298 presented with a native infection. A total of (334/5777) cases developed an infection despite having been vaccinated at least once. Comparing unvaccinated patients with those with at least one vaccination, we find an odds ratio (OR) 2.73, (95% confidence interval (CI) 0.79e9.50) regarding the variable fatal outcome that did not reach statistical significance. Analysing the clinical variables 'CNS symptoms' and 'myelitis', there is no difference between these groups (OR 0.86, 95% CI 0.68e1.08; and OR 1.30, 95% CI 0.74e2.27 respectively). Patients who were vaccinated and had an assumed protection at symptom onset (n ¼ 100) had a higher risk for the development of myelitic symptoms (OR 2.21, 95% CI 1.01e4.86]) than unvaccinated patients. Conclusion: Our findings could neither verify that vaccination breakthrough infections might cause a more severe disease than native infections nor prove a clear antibody-dependent enhancement phenomenon. It remains unclear whether the increased myelitis risk in a subgroup of vaccinated patients is a true effect or confounded.

Broad and potent neutralizing human antibodies to tick-borne flaviviruses protect mice from disease

“…Vaccination requires administration of three separate doses spaced over up to 2 yr, with booster doses recommended at intervals of 3-5 yr (World Health Organization, 2019). Breakthrough TBEV infection occurs despite vaccination (Dobler et al, 2020;Lotrič-Furlan et al, 2017).…”

Clinical Characteristics of Patients with Tick-Borne Encephalitis (TBE): A European Multicentre Study from 2010 to 2017

“…Literature about the severity of TBE breakthrough infection is inconsistent. Previous case reports and case series studies have described a more severe course of disease in patients with vaccination breakthrough infection, while a recent publication investigating a large cohort in Germany did not substantiate this finding [ 57 , 58 ]. The analysis of our cohort showed no significant difference in the distribution of diagnosis or in outcome at discharge when comparing vaccinated or unvaccinated patients; however, the number of breakthrough cases was low.…”

Tick-Borne Encephalitis Virus: A Quest for Better Vaccines against a Virus on the Rise

“…Understanding the cause of breakthrough infections is very important for improving existing vaccines and developing new ones. Although a common definition of vaccination breakthrough infection is missing, TBE patients developing disease despite being vaccinated indicate the inability of the vaccine to induce a protective immune response in any case [ 176 ]. Host-related risk factors, such as advanced age (beyond 60 years), as well as vaccine-related risk factors, such as incomplete primary immunization or delayed first booster doses, may favor vaccination breakthrough infections (reviewed in [ 177 ]).…”

“…Host-related risk factors, such as advanced age (beyond 60 years), as well as vaccine-related risk factors, such as incomplete primary immunization or delayed first booster doses, may favor vaccination breakthrough infections (reviewed in [ 177 ]). Regarding TBEV vaccination, two types of vaccination breakthrough infections have been suggested: patients with inadequate immune response and non-responders [ 176 ].…”