BACKGROUND. Both seasonal and novel avian influenza viruses can result in severe infections requiring hospitalization. Anti-influenza antibodies (Abs) with Fc-mediated effector functions, such as Ab-dependent cellular cytotoxicity (ADCC), are of growing interest in control of influenza but have not previously been studied during severe human infections. As such, the objective of this study was to examine Fc-mediated Ab functions in humans hospitalized with influenza infection. METHODS. Serum Ab response was studied in subjects hospitalized with either pandemic H7N9 avian influenza virus in China (n = 18) or circulating seasonal influenza viruses in Melbourne, Australia (n = 16). Recombinant soluble Fc receptor dimer ELISAs, natural killer (NK) cell activation assays, and Ab-dependent killing assays with influenza-infected target cells were used to assess the Fc functionality of anti-influenza hemagglutinin (HA) Abs during severe human influenza infection. RESULTS. We found that the peak generation of Fc functional HA Abs preceded that of neutralizing Abs for both severe H7N9 and seasonal influenza infections. Subjects who succumbed to complications of H7N9 infection demonstrated reduced HA-specific Fc receptor-binding Abs (in magnitude and breadth) immediately prior to death compared with those who survived. Subjects who recovered from H7N9 and severe seasonal influenza infections demonstrated increased Fc receptor-binding Abs not only against the homologous infecting strain but against HAs from different influenza A subtypes. CONCLUSION. Collectively, survivors of severe influenza infection rapidly generate a functional Ab response capable of mediating ADCC against divergent influenza viruses. Broadly binding HA Abs with Fc-mediated functions may be a useful component of protective immunity to severe influenza infection.
[1]Univ Melbourne, Peter Doherty Inst Infect & Immun, Dept Microbiol & Immunol, Melbourne, Vic, Australia;
[2]Fudan Univ, SPHCC, 138 Yixueyuan Rd, Shanghai, Peoples R China;
[3]Fudan Univ, Inst Biomed Sci, Key Lab Med Mol Virol, Minist Educ Hlth,Shanghai Med Coll, 138 Yixueyuan Rd, Shanghai, Peoples R China;
[4]Burnet Inst, Melbourne, Vic, Australia;
[5]Univ Melbourne, Peter Doherty Inst Infect & Immun, WHO Collaborating Ctr Reference & Res Influenza, Melbourne, Vic, Australia;
[6]Univ New South Wales Australia, Kirby Inst Infect & Immun, Infect Analyt Program, Sydney, NSW, Australia;
[7]Monash Univ, Dept Allergy Immunol & Resp Med, Alfred Hosp, Melbourne, Vic, Australia;
[8]Monash Univ, Cent Clin Sch, Melbourne, Vic, Australia;
[9]Monash Univ, Alfred Hlth, Infect Prevent & Healthcare Epidemiol Unit, Melbourne, Vic, Australia;
[10]Monash Univ, Sch Publ Hlth & Prevent Med, Melbourne, Vic, Australia;
[11]Monash Univ, Melbourne Sexual Hlth Ctr, Melbourne, Vic, Australia;
[12]Monash Univ, Dept Infect Dis, Alfred Hlth, Cent Clin Sch, Melbourne, Vic, Australia;
[13]Univ Melbourne, ARC Ctr Excellence Convergent Bio Nanosci & Techn, Parkville, Vic, Australia
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