Posted in influenza, Resource

Innate gene signature distinguishes humoral versus cytotoxic responses to influenza vaccination

Hierarchical clustering showing how the changes in transcript levels at day 1 differ between patients. Two distinct clusters, C1 and C2 are seen. Source from Gonçalves et al., JCI, 2020.

Does the vaccine administration route affect host responses to vaccines? In this paper, Gonçalves et al investigates how vaccine administration via the intramuscular (i.m.), intradermal (i.d.) and transcutaneous (t.c.) routes affects innate and adaptive responses to the inactivated influenza vaccine.

60 healthy subjects, 18–45 years old recruited to compare the immunogenicity of the 2012–2013 seasonal trivalent inactivated influenza vaccine (TIV) administered by the t.c. (20 subjects), i.d. (20 subjects) and i.m. (20 subjects) routes.

The i.m. and i.d. route generated higher neutralising antibodies compared to the t.c. route. Higher vaccine-specific CD8+GRZ+ T cells was seen after t.c. and i.d. vaccination compared to i.m. However, vaccine-specific CD8+ T-cell responses were not significantly different between the conditions.

More differentially expressed genes were detected in i.m. and i.d., as compared to t.c.. Two distinct gene signature clusters (C1 and C2; see above figure) were observed, but the clusters did not segregate by vaccine administration route. The C1-C2 dichotomy is attributed to genes involved in multiple pathways, such as those for antigen-presentation, DC maturation, and IFN signaling, where subjects in the C1 cluster expressed higher levels of these transcripts (see above figure).

Instead, C1 and C2 clusters had significant differences in humoral and CD8+GRZ+ T cell responses. Of note, C1 individuals had significantly higher influenza-specific MN antibody titers, but lower frequency of TIV-specific CD8+GRZ+ T cell responders.

80 transcripts related to interferon signaling and antigen presentation pathways are correlated with neutralising antibody responses. On the other hand, 31 transcripts related to metabolic pathways were correlated with TIV-specific CD8+GRZ T cell responses.

The top positively correlated genes with antibody responses are CXCR2P1, C2, and CKS1B and the top negatively correlated genes are PRKAA1 and TMEM8B. The top genes involved in correlation with CD8+GRZ+ T cell response were MAP2K5, PVRL1, SARM1, and CXCR4.

Data deposited in ArrayExpress with the accession code E-MTAB-7741.

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