Geißlreiter et al.
High neutralizing antibody mismatch as a possible reason for vaccine failure in two children with severe tick-borne encephalitis
Ticks Tick Borne Dis. 2023;14(4):102158. doi:10.1016/j.ttbdis.2023.102158

TBE vaccination is highly effective, but vaccination breakthrough (VBT) infections occur in a small percentage of vaccinees. Two VBTs in two adolescents aged 13 and 16 years, who had been immunized with the TBE vaccine Encepur (based on strain K23), have been analyzed in more detail.

At the onset of clinical symptoms, both patients were negative or borderline when IgM antibodies were tested against the envelope glycoprotein E or against the non-structural protein 1 (NS-1) but became positive at day 10 and 12 respectively. Both patients also exhibited a great increase in TBE antibody IgG during the course of infection.  

No TBE virus could be isolated from the patients’ cerebrospinal fluid, but from ticks of the respective area of infection. Both isolated virus strains were of European subtype and showed about 1% difference at nucleotide level between each other and the TBE vaccine strain K23. TBE neutralization tests gave positive results against the vaccine strain (1:160 and 1:640 respectively), while the titers were lower against the strains isolated from the ticks (1:20 and 1:80 respectively). NT titers were also higher when the vaccine strain Neudörfl was used (160 and 640 respectively one or eight days after admission) in comparison to the isolated virus strains from the supposed infection site.

The authors discussed that a mismatch of neutralizing antibodies against wild-type TBE virus strains might be at least partially responsible for the vaccine failure. The two isolated wild-type strains differed from the vaccine strain by 2 to 4 amino acid exchanges in the glycoprotein E. In further studies, the disease-causing wild-type strain should be identified, either in the patient or from ticks at the site of infection in order to analyze the possibility that certain wild-type strains may be less well neutralized by antibodies produced in response to vaccine strains and to help to clarify whether current vaccines may possibly be optimized by adaption.

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