Adjuvants recognized by toll-like receptors inhibit the induction of polarized type 2 T cell responses by natural attachment (G) protein of respiratory syncytial virus

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• 作者：Hancock ; Gerald E. ; Heers ; Kristen M. ; Pryharski ; Karin S. ; Smith ; Jason D. ; Tiberio ; Lorrie
• 关键词：Adjuvant ; Attachment (G) protein ; Eosinophils ; Unmethylated CpG ; Respiratory syncytial virus (RSV) ; T cells ; Toll-like receptor (TLR) ; Subunit vaccines
• 刊名：Vaccine
• 出版年：2003
• 出版时间：October 1, 2003
• 年：2003
• 卷：21
• 期：27-30
• 页码：4348-4358
• 全文大小：173 K

文摘

Immunization with native fusion (F) protein from respiratory syncytial virus (RSV) adsorbed to alum adjuvant generates greater than fourfold rises in serum neutralizing antibody titers in approximately 50 % of seropositive humans. Using BALB/c mice we demonstrate herein that enhanced neutralization titers and accelerated clearance of virus from the lungs after challenge are possible if the attachment (G) glycoprotein is added to F protein-based vaccines. We further reveal for the first time that polarized type 2 T cell responses and immunopathology associated with G protein are inhibited by adjuvants recognized by toll-like receptors (TLR). Co-formulation with compounds that targeted TLR-2, TLR-3, TLR-4, or TLR-9 elicited significantly diminished type 2 T cell responses that caused granulocytic inflammation and eosinophilia in the airways after challenge. These results were not observed with recombinant IL-12 or QS-21. The data are important for improving combination vaccines for RSV.