Abstract
The influenza A H7N9 virus outbreak in Eastern China in the spring of 2013 represented a novel, emerging avian influenza transmission to humans. While clinical and microbiological features of H7N9 infection have been reported in the literature, the current study investigated acute cytokine and antibody responses in acute H7N9 infection. Between March 27, 2013 and April 23, 2013, six patients with confirmed H7N9 influenza infection were admitted to Drum Tower Hospital, Nanjing, China. Acute phase serum cytokine profiles were determined using a high-throughput multiplex assay. Daily H7 hemagglutinin (HA)-specific IgG, IgM, and IgA responses were monitored by ELISA. Neutralizing antibodies specific for H7N9 viruses were determined against a pseudotyped virus expressing the novel H7 subtype HA antigen. Five cytokines (IL-6, IP-10, IL-10, IFNγ, and TNFα) were significantly elevated in H7N9-infected patients when compared to healthy volunteers. Serum H7 HA-specific IgG, as well as IgM and IgA responses, were detected within 8 days of disease onset and increased in a similar pattern during acute infection. Neutralizing antibodies developed shortly after the appearance of binding antibody responses and showed similar kinetics as a fraction of the total H7 HA-specific IgG responses. H7N9 infection resulted in hallmark serum cytokine increases, which correlated with fever and disease persistence. The novel finding of simultaneous development of IgG, IgM, and IgA responses in acute H7N9 infection points to the potential for live influenza viruses to elicit fast and potent protective antibodies to limit the infection.
Highlights
Given the importance of antibody responses in protection immunity against influenza and the role of cytokines in modulating innate immune responses in patients infected with influenza viruses, the current report analyzed serum H7 HA-specific binding antibody responses starting within 6–11 days after onset of fever in H7N9 patients, the development of neutralizing antibodies, and serum levels of specific cytokines in a cohort of six H7N9-infected patients admitted to a hospital in Nanjing during the peak of the 2013 outbreak
Due to limited knowledge in the existing literature regarding acute immune responses to an outbreak of a novel avian influenza in humans, information described in this report may be useful for a better understanding on the development of acquired and innate immunities early after avian influenza infection
During the initial H7N9 outbreak in the spring of 2013, six patients with confirmed H7N9 infection were admitted to the Nanjing Drum Tower Hospital (Table 1) [3,32]
Summary
An emerging Type A influenza H7N9 infection in humans, which started in early 2013, has continued in China and represents another major threat to global health [1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20]. While the clinical symptoms and features of isolated H7N9 virus strains have recently been described, information on early immune responses in acutely H7N9-infected patients is limited [5,6,7,24,25,26,27]. Due to limited knowledge in the existing literature regarding acute immune responses to an outbreak of a novel avian influenza in humans, information described in this report may be useful for a better understanding on the development of acquired and innate immunities early after avian influenza infection
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