Posted in Hepatitis B, Resource

Transcriptional profiles of adjuvanted hepatitis B vaccines display variable interindividual homogenity but a shared core signature

Clustergram showing similarities and differences in gene expression for different adjuvants. The day 1 and day 31 (day 1 after 2nd dose) for AS01 and AS03 adjuvants cluster together, whereas AS04 and Alum cluster together with the late responses (days 3-7). AS01 and AS03 induces greater number of DEGs compared to AS04 and Alum. Source from: Laurane et al., Science Translational Medicine, 2020

Adjuvants are an important component in inactivated vaccines, as they are known to trigger activation of innate immune responses that is essential for eliciting adaptive immune responses. In this study, Laurane et al., Science Translational Medicine, 2020 investigated how the transcriptional profile in humans is altered by 5 different types of adjuvants, namely:

  1. AS01B (MPL + QS-21)
  2. AS01E (half dose of MPL + QS-21)
  3. AS03 (a-tocopherol + squalene)
  4. AS04 (MPL+Alum)
  5. Alum

They also examined the inter-individual variations in vaccine responses to the different adjuvants. The antigen used is the Hepatitis B virus (HBV) surface antigen (HBs).

112 healthy subjects were given two intramuscular injections of HBs antigen (18 for AS01B, 23 for AS01E, 28 for AS03, 22 for AS04, 21 for Alum). Whole blood transcriptome profiled at 0, 3-6hrs, 1, 14 days after first dose and 0, 3-6hrs, 1, 3, 7 days after second dose. The second dose was given 30 days after first dose.

Most DEGs are detected at day 1 and day 31 post vaccination. Highest number of DEGs were seen in AS01B and AS01E , followed by AS03. Much lesser DEGs were seen with AS04 and Alum. The upregulated DEGs for AS01B, AS01E, and AS03 comprised of genes mostly related to innate immune genes and interferon responses. This is interesting because AS01 and AS03 components are different but yet, they induce transcriptional responses that are converging.

Interestingly, heterogeneity among individual responses for the AS03 recipients was higher compared to AS01 recipients.

Some of the day 1 genes related to innate response, interferon pathway and NK cells are correlated with humoral and cellular responses at day 44. However, this only accounted for <40% of the correlated genes. Genes from other pathways such as cell cycle and metabolism were also associated with the humoral and cellular responses at day 44.