Induction of TLR4-dependent CD8+ T cell immunity by murine β-defensin2 fusion protein vaccines

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• 作者：H.J. Park^a ; ^d ; ¹ ; H. Qin^a ; ^d ; ¹ ; ^{hqin@mdanderson.org} ; S.C. Cha^a ; ^d ; R. Sharma^a ; ^d ; ¹ ; Y. Chung^b ; ^d ; K.S. Schluns^b ; ^d ; S.S. Neelapu^a ; ^d ; W.W. Overwijk^c ; ^d ; P. Hwu^c ; ^d ; L.W. Kwak^a ; ^d
• 关键词：Cancer vaccine ; Defensin beta 2 (mBD2) ; TLR4
• 刊名：Vaccine
• 出版年：2011
• 出版时间：18 April 2011
• 年：2011
• 卷：29
• 期：18
• 页码：3476-3482
• 全文大小：775 K

文摘

Our laboratory previously described the strategy of fusing chemokine receptor ligands to antigens in order to generate immunogenic DNA vaccines. In the present study, we produced mouse β-2 defensin (mBD2) fusion proteins using both ovalbumin (OVA) and gp100 as model antigens. Superior cross-presentation by dendritic cells (DC) was observed for mBD2 fused antigens over unfused antigens in vitro. In vivo, we observed significant increases in the expansion of adoptively transferred antigen-specific MHC class I, but not class II-restricted T cells after immunization with mBD2 fused antigen over antigen alone. This enhanced expansion of class I restricted T cells was Toll-like receptor 4 (TLR4) dependent, but CC chemokine receptor 6 (CCR6) independent. Superior tumor resistance was observed for mBD2-fusion protein vaccines, compared to unfused antigen, in both B16-OVA and B16 tumor models. These data suggest that production of mBD2 fusion proteins is feasible and that the vaccines facilitate in vivo expansion of adoptively transferred T cells through a TLR4-dependent mechanism.