Abstract
BackgroundInfluenza remains a major threat to public health. Live-attenuated influenza vaccines (LAIV) have been shown to be effective, particularly in children. Follicular T helper (TFH) cells provide B-cell help and are crucial for generating long-term humoral immunity. However the role of TFH cells in LAIV-induced immune responses is unknown.MethodsWe collected tonsils, plasma, and saliva samples from children and adults receiving LAIV prior to tonsillectomy. We measured influenza-specific TFH-cell responses after LAIV by flow cytometry and immunohistochemistry. Systemic and local antibody responses were analysed by hemagglutination inhibition assay and enzyme-linked immunosorbent assay.ResultsWe report that LAIV induced early (3–7 days post-vaccination) activation of tonsillar follicles and influenza-specific TFH-cell (CXCR5+CD57+CD4+ T cell) responses in children, and to a lesser extent in adults. Serological analyses showed that LAIV elicited rapid (day 14) and long-term (up to 1 year post-vaccination) antibody responses (hemagglutination inhibition, influenza-specific IgG) in children, but not adults. There was an inverse correlation between pre-existing influenza-specific salivary IgA concentrations and tonsillar TFH-cell responses, and a positive correlation between tonsillar TFH-cell and systemic IgG induction after LAIV.ConclusionsOur data, taken together, demonstrate an important role of tonsillar TFH cells in LAIV-induced immunity in humans.
Highlights
Influenza remains a major threat to public health
We report that Live-attenuated influenza vaccines (LAIV) induced early (3–7 days post-vaccination) activation of tonsillar follicles and influenza-specific TFH-cell (CXCR5+CD57+CD4+ T cell) responses in children, and to a lesser extent in adults
Serological analyses showed that LAIV elicited rapid and long-term antibody responses in children, but not adults
Summary
Plasma, and saliva samples from children and adults receiving LAIV prior to tonsillectomy. We measured influenza-specific TFH-cell responses after LAIV by flow cytometry and immunohistochemistry. All subjects were patients scheduled for elective tonsillectomy due to chronic tonsillitis, tonsillar hypertrophy, or both but otherwise healthy. The study was approved by the Ethical Committee and the Medicines Agency. All participants or their guardians provided written informed consent before inclusion in the study (NCT01866540, www.clinicaltrials.gov). Thirty-four children and 31 adults were vaccinated with trivalent LAIV (Fluenz; AstraZeneca) during the influenza season 2013–2014. The children and adults were divided into 3 groups and vaccinated on specific days before their scheduled tonsillectomy. Age- and gender-matched unvaccinated subjects (6 children and 6 adults) were enrolled as controls
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