Early Induction of Cross-Reactive CD8+ T-Cell Responses in Tonsils After Live-Attenuated Influenza Vaccination in Children

儿童接种减毒活流感疫苗后扁桃体中早期诱导交叉反应性 CD8+ T 细胞反应

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作者:K G-I Mohn, K A Brokstad, S Islam, F Oftung, C Tøndel, H J Aarstad, R J Cox

Background

Live-attenuated influenza vaccine (LAIV) was licensed for prophylaxis of children 2-17 years old in Europe in 2012 and is administered as a nasal spray. Live-attenuated influenza vaccine induces both mucosal and systemic antibodies and systemic T-cell responses. Tonsils are the lymph nodes serving the upper respiratory tract, acting as both induction and effector site for mucosal immunity.

Conclusions

Our findings support the use of LAIV in children to elicit broadly cross-reactive T cells, which are not induced by traditional inactivated influenza vaccines and may provide protection to novel virus strains.

Methods

Here, we have studied the early tonsillar T-cell responses induced in children after LAIV. Thirty-nine children were immunized with trivalent LAIV (containing A/H1N1, A/H3N2, and B viruses) at days 3, 7, and 14 before tonsillectomy. Nonvaccinated controls were included for comparison. Tonsils and peripheral blood (pre- and postvaccination) were collected to study T-cell responses.

Results

Tonsillar and systemic T-cell responses differed between influenza strains, and both were found against H3N2 and B viruses, whereas only systemic responses were observed against A/H1N1. A significant increase in cross-reactive tonsillar CD8+ T cells recognizing conserved epitopes from a broad range of seasonal and pandemic viruses occurred at day 14. Tonsillar T cells showed significant cytokine responses (Th1, Th2, and granulocyte-macrophage colony-stimulating factor). Conclusions: Our findings support the use of LAIV in children to elicit broadly cross-reactive T cells, which are not induced by traditional inactivated influenza vaccines and may provide protection to novel virus strains.

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