Live-Attenuated Influenza Vaccine Induces Tonsillar Follicular T Helper Cell Responses That Correlate With Antibody Induction

Live-Attenuated Influenza Vaccine Induces Tonsillar Follicular T Helper Cell Responses That Correlate With Antibody Induction

Abstract Background Influenza 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...

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Bibliographic Details
Published in:The Journal of infectious diseases Vol. 221; no. 1; pp. 21 - 32
Main Authors: Lartey, Sarah, Zhou, Fan, Brokstad, Karl A, Mohn, Kristin G-I, Slettevoll, Steffen A, Pathirana, Rishi D, Cox, Rebecca J
Format: Journal Article
Language:English
Published: US Oxford University Press 01-01-2020
Subjects:
Antibodies
CD4 antigen
CD57 antigen
Children
CXCR5 protein
Enzyme-linked immunosorbent assay
Flow cytometry
Follicles
Helper cells
Hemagglutination inhibition
Humoral immunity
Immunoglobulin A
Immunoglobulin G
Immunohistochemistry
Influenza
Lymphocytes B
Lymphocytes T
Major and Brief Reports
Public health
Saliva
Tonsil
Vaccines
tonsils
influenza
LAIV
cells
T
antibody responses
TFH cells
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Summary:Abstract Background Influenza 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. Methods We 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. Results We 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. Conclusions Our data, taken together, demonstrate an important role of tonsillar TFH cells in LAIV-induced immunity in humans. Live attenuated influenza vaccine induces rapid influenza-specific tonsillar TFH-cell and antibody responses in children, but is less potent in adults. The magnitude of influenza-specific TFH-cell responses inversely correlated with pre-existing salivary IgA, and directly associated with post-vaccination antibody fold-induction.
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S. L. and F. Z. contributed equally to this work.
ISSN:0022-1899
1537-6613
DOI:10.1093/infdis/jiz321