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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Front+Immunol
2018 ; 9
(ä): 381
Nephropedia Template TP
gab.com Text
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English Wikipedia
Overcoming the Neonatal Limitations of Inducing Germinal Centers through
Liposome-Based Adjuvants Including C-Type Lectin Agonists Trehalose Dibehenate or
Curdlan
#MMPMID29541075
Vono M
; Eberhardt CS
; Mohr E
; Auderset F
; Christensen D
; Schmolke M
; Coler R
; Meinke A
; Andersen P
; Lambert PH
; Mastelic-Gavillet B
; Siegrist CA
Front Immunol
2018[]; 9
(ä): 381
PMID29541075
show ga
Neonates and infants are more vulnerable to infections and show reduced responses
to vaccination. Consequently, repeated immunizations are required to induce
protection and early life vaccines against major pathogens such as influenza are
yet unavailable. Formulating antigens with potent adjuvants, including
immunostimulators and delivery systems, is a demonstrated approach to enhance
vaccine efficacy. Yet, adjuvants effective in adults may not meet the specific
requirements for activating the early life immune system. Here, we assessed the
neonatal adjuvanticity of three novel adjuvants including TLR4 (glucopyranosyl
lipid adjuvant-squalene emulsion), TLR9 (IC31(®)), and Mincle (CAF01) agonists,
which all induce germinal centers (GCs) and potent antibody responses to
influenza hemagglutinin (HA) in adult mice. In neonates, a single dose of HA
formulated into each adjuvant induced T follicular helper (T(FH)) cells. However,
only HA/CAF01 elicited significantly higher and sustained antibody responses,
engaging neonatal B cells to differentiate into GCs already after a single dose.
Although antibody titers remained lower than in adults, HA-specific responses
induced by a single neonatal dose of HA/CAF01 were sufficient to confer
protection against influenza viral challenge. Postulating that the neonatal
adjuvanticity of CAF01 may result from the functionality of the C-type lectin
receptor (CLR) Mincle in early life we asked whether other C-type lectin agonists
would show a similar neonatal adjuvanticity. Replacing the Mincle agonist
trehalose 6,6'-dibehenate by Curdlan, which binds to Dectin-1, enhanced antibody
responses through the induction of similar levels of T(FH), GCs and bone marrow
high-affinity plasma cells. Thus, specific requirements of early life B cells may
already be met after a single vaccine dose using CLR-activating agonists,
identified here as promising B cell immunostimulators for early life vaccines
when included into cationic liposomes.