OBJECTIVES:

Despite the importance of immunological memory for protective immunity against viral infection, whether H7N9-specific antibodies and memory T-cell responses remain detectable years after the original infection is unknown.

METHODS:

A cross-sectional study was conducted to investigate the immune memory responses of H7N9 patients who contracted the disease and survived during the 2013-2016 epidemics in China. Sustainability of antibodies and T-cell memory to H7N9 virus were examined. Healthy subjects receiving routine medical examination in physical examination center were recruited as control.

RESULTS:

A total of 75 survivors were enrolled and classified into four groups based on the time elapsed from illness onset to specimen collection: three months (n=14), 14 months (n=14), 26 months (n=28), and 36 months (n=19). Approximately 36 months after infection, the geometric mean titers of virus-specific antibodies were significantly lower than titers in patients of three months after infection, but 16 of 19 (84.2%) survivors in the 36-month interval had microneutralization (MN) titer > 40. Despite the overall declining trend, the percentages of virus-specific cytokines-secreting memory CD4+ and CD8+ T-cells remained higher in survivors at nearly all time points in comparison with control subjects. Linear regression analysis showed that severe disease (mean titer ratio 2.77, 95%CI 1.17-6.49) was associated with higher hemagglutination inhibition (HI) titer, and female sex for both HI (1.92, 1.02-3.57) and MN (3.33, 1.26-9.09) antibody, whereas female sex (mean percentage ratio 1.69, 95%CI 1.08-2.63), underlying medical conditions (1.94, 95%CI 1.09-3.46), and lack of antiviral therapy (2.08, 95%CI 1.04-4.17) were predictors for higher T-cell responses.

CONCLUSIONS:

Survivors from H7N9 virus infection produced long-term antibodies and memory T-cells responses. Our findings warrant further serological investigation in general and high-risk populations and have important implications for vaccine design and development.