Factors Determining Immunological Response to Vaccination against Tick-Borne Encephalitis Virus in Older Individuals

Abstract

We performed a cross-sectional study including 533 individuals (median age 61) from the highly TBE endemic Åland Islands in the archipelago between Sweden and Finland. Blood samples, questionnaires and vaccination records were obtained from all study participants. The aim was to investigate if there was any association between TBEV antibody titer and 12 health-related factors. Measurement of TBEV IgG antibodies was performed using two commercial ELISA assays (Enzygnost and Immunozym), and a third in-house rapid fluorescent focus inhibition test was used to measure TBEV neutralizing antibodies. The age of the individual and the number of vaccine doses were the two most important factors determining the immunological response to vaccination. The response to each vaccine dose declined linearly with increased age. A 35 year age difference corresponds to a vaccine dose increment from 3 to 4 to achieve the same immunological response. Participants previously vaccinated against other flaviviruses had lower odds of being seropositive for neutralizing TBEV antibodies on average, while participants with self-reported asthma had higher odds of being seropositive. By comparing the 3 serological assays we show that the Enzygnost and Immunozym assay differ due to choice of cutoffs, but not in overall accuracy.

Tick‐borne encephalitis in patients vaccinated against this disease

“…Of the 39 patients in the present study who developed breakthrough TBE, 22 (56.4%) were male, a sex ratio similar to that for all notified TBE cases in Slovenia (of 3304 patients ≥15 years old registered with TBE in Slovenia in 2000–2015, the proportion of males was 57.2%). However, vaccinated patients were older than 3304 patients registered with TBE in the same time period: median 59 (20–83) versus 44 (15–75+) years, respectively , which corresponds well with other reports indicating higher age in previously vaccinated patients with breakthrough TBE and implies less effective protection in older people, possibly due to decreased immunological responsiveness to vaccination and increased risk of vaccine failure . The exact mechanisms remain unknown.…”

“…The absence of the expected antibody pattern was not a surprise for a patient who had received only two doses of vaccine (14 days after the second dose about 85% of vaccines develop protective antibodies, 15% do not) [4], but was somewhat unexpected for the patient who had received three doses of basic vaccination (although the last dose was 15 years before the onset of TBE) and who reacted serologically as an immunologically na€ ıve person. Nevertheless, our results further corroborate previous reports [7,9,[27][28][29] that primary vaccine failure (complete nonresponsiveness to vaccination) is rare and that the large majority of TBE vaccination failures are secondary, that is the initial response to vaccination is not maintained. At the time of TBEV infection that resulted in breakthrough TBE we had no information on the immunological status of our 39 patients and therefore can only surmise that their protective antibody levels were too low and the anamnestic response too slow to prevent the disease from developing [14].…”

“…Our study shows that TBE has a more severe course of acute illness in previously vaccinated than in unvaccinated persons, as indicated by quantitative evaluation of the severity of illness and simple clinical classification, as well as by the presence of individual clinical findings indicative of severe disease, including duration of hospitalization, proportion of patients needing ICU treatment, and proportion of patients having evident conscious disturbances, urine retention, and pareses of one or more extremities and/or trunk. As suggested previously , it appears that vaccination that does not protect an individual may have an adverse effect on the outcome. In the present study, we did not find an obvious alternative explanation for the more severe illness in previously vaccinated patients.…”

EAN consensus review on prevention, diagnosis and management of tick‐borne encephalitis

“…Studies on persistence of immunity show a long-term seroprotection that may last up to 10 years, but there is an age-related decline in immunocompetence since the seroprotection rates in people over 50-60 years were significantly lower than in younger individuals [69,[98][99][100]. In a Swedish study in older individuals, age and the number of vaccine doses were shown as the most important factors determining the immunological response [101]. However, despite decreasing levels, healthy elderly people are able to produce antibodies in response to vaccination with similar avidity and functional activity as young individuals [102].…”

Comparison of Two Commercial Tick-Borne Encephalitis Virus IgG Enzyme-Linked Immunosorbent Assays

“…The K23 and Neudoerfl strains are used in the European vaccines Encepur (Novartis Vaccines and Diagnostics GmbH & Co., Marburg, Germany) and FSME-Immun (Baxter AG, Vienna, Austria), respectively. Both vaccines induce neutralizing antibodies against all three subtypes of TBEV, but there might be some differences in reactivity depending on whether homologous or heterologous coating antigens were used for the vaccine (14,15).…”