Listeria monocytogenes delivery of HPV-16 major capsid protein L1 induces systemic and mucosal cell-mediated CD4+ and CD8+ T-cell responses after oral immunization

单核细胞增生李斯特菌递送 HPV-16 主要衣壳蛋白 L1 在口服免疫后诱导全身和粘膜细胞介导的 CD4+ 和 CD8+ T 细胞反应

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作者:Waleed Mustafa, Paulo Cesar Maciag, Zhen-kun Pan, Jessica R Weaver, Yuhong Xiao, Stuart N Isaacs, Yvonne Paterson

Abstract

Neutralizing antibodies are thought to be required at mucosal surfaces to prevent human papillomavirus (HPV) transmission. However, the potential for cell-mediated immunity in mediating protection against HPV infection has not been well explored. We generated recombinant Listeria monocytogenes (Lm) constructs that secrete listeriolysin O (LLO) fused with overlapping N-terminal (LLO-L1(1-258)) or C-terminal (LLO-L1(238-474)) fragments of HPV type 16 major capsid protein L1 (HPV-16-L1). Oral immunization of mice with either construct induced IFN-gamma-producing CD8+ and CD4+ T cells in the spleen and in the Peyer's patches with the C-terminal construct. Oral immunization with both constructs resulted in diminished viral titers in the cervix and uterus of mice after intravaginal challenge with vaccinia virus expressing HPV-16-L1.

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