M.-J.Ma, X.-X.Wang, M.-N.Wu, X.-J.Wang, C.-J.Bao, H.-J.Zhang, Y.Yang, K.Xu, G.-L.Wang, M.Zhao, W.Cheng, W.-J.Chen, W.-H.Zhang, L.-Q.Fang, W.J.Liu, E.-F.Chen, W.-C.Cao
Clinical Microbiology and Infection
June 20, 2019
ABSTRACT
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 individuals receiving routine medical examinations in a physical examination centre 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: 3 months (n = 14), 14 months (n = 14), 26 months (n = 28) and 36 months (n = 19). Approximately 36 months after infection, the geometric mean titres of virus-specific antibodies were significantly lower than titres in patients 3 months after infection, but 16 of 19 (84.2%) survivors in the 36-month interval had microneutralization (MN) titres ≥40. Despite the overall declining trend, the percentages of virus-specific cytokine-secreting memory CD4+ and CD8+ T cells remained higher in survivors at nearly all time-points in comparison with control individuals. Linear regression analysis showed that severe disease (mean titre ratio 2.77, 95% CI 1.17–6.49) was associated with higher haemagglutination inhibition (HI) titre 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 of H7N9 virus infection produced long-term antibodies and memory T-cell responses. Our findings warrant further serological investigation in general and high-risk populations and have important implications for vaccine design and development.