Relationship of Preexisting Influenza Hemagglutination Inhibition, Complement-Dependent Lytic, and Antibody-Dependent Cellular Cytotoxicity Antibodies to the Development of Clinical Illness in a Prospective Study of A(H1N1)pdm09 Influenza in Children

Abstract The hemagglutination inhibition (HAI) antibody titer is considered the primary immune correlate of protection for influenza. However, recent studies have highlighted the limitations on the use of the HAI titer as a correlate in at-risk populations such as children and older adults. In addition to the neutralization of cell-free virus by antibodies to hemagglutinin and interference of virus release from infected cells by antibodies to neuraminidase, influenza virus-specific antibodies specifically can bind to infected cells and lyse virus-infected cells through the activation of complement or natural killer (NK) cells, via antibody-dependent cellular cytotoxicity (ADCC) or complement-dependent lysis (CDL). We evaluated preexisting HAI, CDL, and ADCC antibodies in young children enrolled in a prospective cohort study of dengue during the epidemic with influenza A(H1N1)pdm09 virus to determine associations between preexisting antibodies and the occurrence of clinical or subclinical influenza virus i...