Characterization of antibody and memory T-cell response in H7N9 survivors: a cross-sectional analysis

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 2013e2016 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 ¼ 14), 14 months (n ¼ 14), 26 months (n ¼ 28) and 36 months (n ¼ 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 þ and CD8 þ 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 1.17e6.49) was associated with higher haemagglutination inhibition (HI) titre and female sex for both HI (1.92, 1.02e3.57) and MN (3.33, 1.26e9.09) antibody, whereas female sex (mean percentage ratio 1.69, 95% CI 1.08e2.63), underlying medical conditions (1.94, 95% CI 1.09e3.46) and lack of antiviral therapy (2.08, 95% CI 1.04e4.17) 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.

Avian influenza A (H7N9) virus: from low pathogenic to highly pathogenic

“…In a cohort of H7N9 survivors who were followed up for 15 months after infection, although the H7N9-specific antibody concentrations declined over time, the frequency of virus-specific IFN-g-secreting T cells increased within 1 year of infection [89]. This phenomenon was confirmed in another cross-sectional study involving survivors at 36 months after infection [90]. This increasing trend over time within 1 year of infection was more obvious in patients aged ≥ 60 years and in critically ill patients requiring ventilation during their infections.…”

Human antibody recognition of H7N9 influenza virus HA following natural infection

“…Serology studies have shown that human H7N9 virus infection stimulates the induction of H7-reactive antibody responses that persist for at least several years ( 10 , 11 , 24 , 38 ). Kinetic monitoring of such responses revealed that heterosubtypic H7 and H3 binding/neutralizing antibody responses typically appear and peak earlier than H7 subtype responses, likely mediated by memory recall of H3-reactive clones ( 24 ).…”

Specificity, kinetics and longevity of antibody responses to avian influenza A(H7N9) virus infection in humans

“…In another cross-sectional study, Ma et al reported that HAI GMT was near 40 at about 26 months after illness onset, which was similar to our findings. 21 For the pooled analyses of antibody kinetics, data for antigens that were antigenically-matched to circulating strains are preferred. However, there might be antigen-specific differences in HAI titers, which could affect the results.…”

“…37 For A(H7N9) virus-specific antibody responses after discharge in survivors, Ma et al found no association between disease severity and antibody response in one study, 20 while reported that severe disease was associated with higher HAI titer after discharge in another study. 21 Antibody responses to A(H5N1) virus infection after recovery have been reported to be lower in patients with asymptomatic infection than in those with severe illness. 30 Previous studies in A(H7N9) virus infected patients indicate that effective cross-reactive T cell memory is important for protection against severe influenza disease caused by newly emerging influenza A viruses.…”

“…Ma et al described the dynamics of the antibody response to A(H7N9) virus over a year post illness onset in 25 patients, 20 they also characterized the antibody response to A(H7N9) virus up to 36 months after illness onset in a cross-sectional analysis. 21 However, the longitudinal dynamics of the antibody response beyond one year have not been determined.…”