HBsAg-specific CD4 T cell response in HBV vaccinated individuals

Background: The global implementation of prophylactic hepatitis B virus (HBV) vaccination in 1984 led to a significant decrease in HBV infections. It also offers the opportunity to study immunological mechanisms of immune memory maintenance. While most individuals develop strong anti-HBs responses, these titers are not universally maintained. Although the role of CD4 T cells in supporting antibody development and maintenance is well established, they have not been thoroughly investigated in this specific context.

Methods: We screened our biobank for samples from anti-HBs+/anti-HBc- individuals carrying the HLA DRB1*0101 or DRB1*0701 alleles. For ex vivo detection of HBsAg-specific CD4 T cells, we used peptide-loaded MHC class II tetramers restricted to the aforementioned alleles. In addition, we performed in vitro stimulation with overlapping peptides spanning the HBsAg for 10 days followed by an intracellular cytokine staining.

Results: This is an ongoing study and additional results will be presented at the conference. So far, we analyzed 47 individuals. 32% (15/47) had detectable HBsAg-specific CD4 T cells directly ex vivo. The highest frequencies were observed in individuals with anti-HBs titers>100 IU/l. Phenotypic analyses for different memory subpopulations are currently ongoing. Following in vitro HBsAg stimulation, we identified cytokine-producing CD4 T cells in 70% of the individuals (n=10, experiments ongoing).

Conclusions: Our preliminary results suggest that the frequency of HBsAg-specific CD4 T cells is associated with the anti-HBs titers in vaccinated individuals. Whether this is driven by specific memory subsets and in how far this correlates with individual vaccine history is currently being investigated.

Publication History

Article published online:
20 January 2025