Th212 - T Cell Transcriptional Signatures of Influenza A/H3N2 Humoral Response to High Dose Influenza and Adjuvanted Influenza Vaccine in Older Adults

Iana Haralambieva, MD, PhD – Research Associate, Vaccine Research Group, Mayo Clinic; Gregory Poland, MD – Consultant, Vaccine Research Group, Mayo Clinic; Richard Kennedy, PhD – Associate Consultant, Vaccine Research Group, Mayo Clinic

Abstract Text: Influenza poses a major health risk for the elderly, with increases in morbidity/mortality with age. >90% of influenza-associated deaths occur in individuals ≥65 yrs of age and are predominantly associated with influenza A/H3N2.
The objective of our study was to identify CD4+Th cell transcriptomic genes/signatures associated with antibody (Ab) response, age, sex, BMI, and CMV IgG-serostatus to high-dose (HDFlu) and adjuvanted (MF59Flu) influenza vaccines in older adults.
A cohort of 234 healthy adults (median age 71.5: IQR 67.9-76.0 yrs), immunized with HDFlu or MF59Flu was enrolled.
Day 0 median influenza A/H3N2-specific HAI titers (1/40; IQR 1/40-1/80) demonstrated the presence of pre-existing Abs. Overall CMV seroprevalence was 56%, and higher (p=0.01) in women (58.2%) than in men (52.3%). There were marginally significantly higher HAI titers observed to HDFlu compared to MF59Flu at Day 28-Day 0 (p=0.06).
We found a negative correlation between CD4+Th cell gene expression and CMV-serostatus for several immune-related genes: TRAIP/TRIM27/ILK/CTSS, r<-0.22. Age-dependent correlations were found between HAI and expression of immunologically-relevant genes (KPNA5/ZFP90/ICAM2). We also discovered vaccine type-specific expression profiles in genes with known immune function: CaMKIV that encodes the calcium/calmodulin-dependent serine/threonine kinase IV (p=0.0008, q=0.1575); its regulator the TMEM38B/transmembrane protein 38B; and the transcriptional coactivator CBP/CREB binding protein, associated with HAI response. The most significant gene associated with Ab titer change to both HDFlu (p=2.12E-13) and MF59Flu (p=1.79E-09) was the TXNIP/thioredoxin interacting antiviral protein.
In conclusion, our findings provide evidence that differential Ab response to influenza vaccination is associated with gene expression profiles that differ between vaccines.