title: Antibody-Dependent Cell-Mediated Cytotoxicity Epitopes on the Hemagglutinin Head Region of Pandemic H1N1 Influenza Virus Play Detrimental Roles in H1N1-Infected Mice.
abstract: Engaging the antibody-dependent cell-mediated cytotoxicity (ADCC) for killing of virus-infected cells and secretion of antiviral cytokines and chemokines was incorporated as one of the important features in the design of universal influenza vaccines. However, investigation of the ADCC epitopes on the highly immunogenic influenza hemagglutinin (HA) head region has been rarely reported. In this study, we determined the ADCC and antiviral activities of two putative ADCC epitopes, designated E1 and E2, on the HA head of a pandemic H1N1 influenza virusin vitroand in a lethal mouse model. Our data demonstrated that sera from the E1-vaccinated mice could induce high ADCC activities. Importantly, the induction of ADCC response modestly decreased viral load in the lungs of H1N1-infected mice. However, the elevated ADCC significantly increased mouse alveolar damage and mortality than that of the PBS-vaccinated group (P< 0.0001). The phenotype was potentially due to an exaggerated inflammatory cell infiltration triggered by ADCC, as an upregulated release of cytotoxic granules (perforin) was observed in the lung tissue of E1-vaccinated mice after H1N1 influenza virus challenge. Overall, our data suggested that ADCC elicited by certain domains of HA head region might have a detrimental rather than protective effect during influenza virus infection. Thus, future design of universal influenza vaccine shall strike a balance between the induction of protective immunity and potential side effects of ADCC.
authors.affiliation: Department of Microbiology, The University of Hong Kong , Hong Kong.
authors.forename: Zi-Wei
authors.initials: ZW
authors.lastname: Ye
authors.affiliation: Department of Microbiology, The University of Hong Kong , Hong Kong.
authors.forename: Shuofeng
authors.initials: S
authors.lastname: Yuan
authors.affiliation: Department of Microbiology, The University of Hong Kong , Hong Kong.
authors.forename: Kwok-Man
authors.initials: KM
authors.lastname: Poon
authors.affiliation: Department of Microbiology, The University of Hong Kong , Hong Kong.
authors.forename: Lei
authors.initials: L
authors.lastname: Wen
authors.affiliation: Department of Microbiology, The University of Hong Kong , Hong Kong.
authors.forename: Dong
authors.initials: D
authors.lastname: Yang
authors.affiliation: Department of Microbiology, The University of Hong Kong , Hong Kong.
authors.forename: Zehua
authors.initials: Z
authors.lastname: Sun
authors.affiliation: Department of Microbiology, The University of Hong Kong , Hong Kong.
authors.forename: Cun
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Microbiology, The University of Hong Kong , Hong Kong.
authors.forename: Meng
authors.initials: M
authors.lastname: Hu
authors.affiliation: Department of Microbiology, The University of Hong Kong , Hong Kong.
authors.forename: Huiping
authors.initials: H
authors.lastname: Shuai
authors.affiliation: Department of Microbiology, The University of Hong Kong, Hong Kong; State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Microbiology, The University of Hong Kong , Hong Kong.
authors.forename: Mei-Yun
authors.initials: MY
authors.lastname: Zhang
authors.affiliation: Department of Microbiology, The University of Hong Kong , Hong Kong.
authors.forename: Bo-Jian
authors.initials: BJ
authors.lastname: Zheng
authors.affiliation: Department of Microbiology, The University of Hong Kong, Hong Kong; State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong.
authors.forename: Hin
authors.initials: H
authors.lastname: Chu
authors.affiliation: Department of Microbiology, The University of Hong Kong, Hong Kong; State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong; Research Centre of Infection and Immunology, The University of Hong Kong, Hong Kong; Carol Yu Centre for Infection, The University of Hong Kong, Hong Kong.
authors.forename: Kwok-Yung
authors.initials: KY
authors.lastname: Yuen
keywords: H1N1 influenza virus; antibody-dependent cell-mediated cytotoxicity; hemagglutinin; lung damage; mice