Aregay et al.
Tick-borne encephalitis vaccine breakthrough infections induce aberrant T cell and antibody responses to non-structural proteins. npj Vaccines. 2024;9(1):141. doi: 10.1038/s41541-024-00936-7
TBE vaccines are highly effective; however, vaccine breakthrough (VBT) infections occur in a small proportion of vaccinated individuals. An international team of scientists investigated whether TBE virus-specific antibody and T-cell levels in convalescent samples (from 59 unvaccinated and 10 VBT cases) correlated with disease severity during acute TBE illness and the presence of neurological sequelae at later stages. Additionally, the team analyzed how prior vaccination affected immunological and clinical outcomes in VBT cases. In particular, they focused on antibodies targeting domain III of glycoprotein E, which has neutralizing capacity and contributes to protective immunity, as well as non-structural protein 1 (NS1), which also induces immune responses that may partially contribute to immunity.
The study found that VBT cases experienced moderate to severe disease. Convalescent NS1 antibody levels were lower in VBT cases compared to unvaccinated TBE patients. Patients who had severe disease showed the lowest antibody levels against EDIII and NS1 years later, suggesting that these antibodies provided some protection against developing severe TBE.
T-cell responses to NS1 were higher in VBT cases than in unvaccinated patients. However, it remains unclear whether virus-specific T-cells have protective effects or might contribute to the pathogenesis of TBE virus.
The authors speculate that in VBT cases, vaccine-induced antibody levels may have decreased to non-protective levels, and the residual low concentration of antibodies could have led to antibody-dependent enhancement of infection.