The immunological mechanisms behind the improvements in serological reactions are unknown of heterologous vaccines against avian influenza. An exploratory study was conducted of the immune response following 1 dose of A/H7N9 inactivated influenza vaccine in individuals who were inactivated with A/H7N7 influenza 8 years previously or A/H7-naïve influenza. ELISA, A/H7N7 specific memory B and antibodies separating cells were evaluated at the baseline and eight day and 28 day after vaccination, at ELISpot, with concentrations of ELISA Plasma IL-6 and IL-21 as well as T cell frequency expressing A/H7N7 specific memory B, and antibody secretion cells, at Baseline, and in Day1 and 28 Days. The similarity of these measurements to serological reactions of the Day29 raise vaccine was measured.

Plasma IL-6 concentration on Day9 was significantly associated with H7N7 and H7N9 HAI antibody levels and the proportion of T cells expressing IL-21 on D9 was significantly correlated with H7N9 HAI antibody seroconversion. No significant correlations have been identified with other immunological markers. The study also identified a connection between plasma IL-6 and IL-21 and serological responses for heterologous primary vaccinations against avian influenza.