An integrated multi-study analysis of serum HAI antibody responses to Ann Arbor strain live attenuated influenza vaccine in children and adults

Serum hemagglutination-inhibition (HAI) antibodies have been associated with protection from influenza infection. HAI antibody responses to live attenuated influenza vaccines (LAIVs) and their role in protection are not fully elucidated. This study characterizes HAI titers for LAIV. Serum HAI data were pooled from 40 LAIV clinical trials enrolling subjects aged 2–49 years. Using pre- and postvaccination titers, geometric mean fold rises (GMFRs) and seroresponse rates (⩾4-fold rise) were determined by age and baseline serostatus (seronegative ⩽8, seropositive >8). Responses were generally evaluated after 2 doses for those 2–8 years of age and after 1 dose for those 9–49 years of age. Data were available for 6909 children and 3444 adults. A total of 20 different LAIV formulations were used, representing 6 H1N1 strains, 9 H3N2 strains, 7 B/Yamagata lineage strains and 2 B/Victoria lineage strains. GMFRs were modest overall; GMFRs were higher in children versus adults and higher in baseline seronegatives versus baseline seropositives. This difference was greatest among children, with GMFRs ranging from 2.2 to 5.9 among seronegative and 1.2–1.5 among seropositive children. HAI responses were modest overall, higher in seronegative individuals (10.8–61.6%) relative to seropositive (1.9–17.0%), and higher in children relative to adults. Postvaccination HAI titers were below those associated with protection for inactivated influenza vaccines. The results suggest that LAIV-induced protection is mediated primarily by mucosal antibody and T-cell immunity, although serum HAI has value as strain-specific marker of response to vaccination, particularly among seronegative individuals.