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使用基于DNA/改良痘苗病毒安卡拉病毒载体的疫苗进行口服和肌肉注射同时初免/舌下加强免疫,可在幼年恒河猴中诱导猿猴免疫缺陷病毒特异性的全身和黏膜免疫反应。

A simultaneous oral and intramuscular prime/sublingual boost with a DNA/Modified Vaccinia Ankara viral vector-based vaccine induces simian immunodeficiency virus-specific systemic and mucosal immune responses in juvenile rhesus macaques.

作者信息

Curtis Alan D, Jensen Kara, Van Rompay Koen K A, Amara Rama R, Kozlowski Pamela A, De Paris Kristina

机构信息

Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.

California National Primate Research Center, University of California, Davis, California.

出版信息

J Med Primatol. 2018 Oct;47(5):288-297. doi: 10.1111/jmp.12372. Epub 2018 Sep 11.

Abstract

BACKGROUND

A pediatric vaccine to prevent breast milk transmission of human immunodeficiency virus (HIV) may generate greater immune responses at viral entry sites if given by an oral route.

METHODS

We compared immune responses induced in juvenile macaques by prime/boosting with simian immunodeficiency virus (SIV)-expressing DNA/modified vaccinia Ankara virus (MVA) by the intramuscular route (IM), the oral (O)/tonsillar routes (T), the O/sublingual (SL) routes, and O+IM/SL routes.

RESULTS

O/T or O/SL immunization generated SIV-specific T cells in mucosal tissues but failed to induce SIV-specific IgA in saliva or stool or IgG in plasma. IM/IM or O+IM/SL generated humoral and cellular responses to SIV. IM/IM generated greater frequencies of T in spleen, but O+IM/SL animals had higher avidity plasma IgG and more often demonstrated mucosal IgA responses.

CONCLUSION

These results suggest that codelivery of HIV DNA/MVA vaccines by the oral and IM routes might be optimal for generating both systemic and mucosal antibodies.

摘要

背景

一种预防人类免疫缺陷病毒(HIV)通过母乳传播的儿科疫苗,如果通过口服途径给药,可能会在病毒进入部位产生更强的免疫反应。

方法

我们比较了通过肌肉注射(IM)、口服(O)/扁桃体途径(T)、口服/舌下(SL)途径以及口服+肌肉注射/舌下途径,用表达猿猴免疫缺陷病毒(SIV)的DNA/改良痘苗病毒安卡拉(MVA)进行初免/加强免疫后,幼年猕猴体内诱导产生的免疫反应。

结果

口服/扁桃体或口服/舌下免疫在黏膜组织中产生了SIV特异性T细胞,但未能在唾液或粪便中诱导产生SIV特异性IgA,也未能在血浆中诱导产生IgG。肌肉注射/肌肉注射或口服+肌肉注射/舌下免疫产生了针对SIV的体液和细胞免疫反应。肌肉注射/肌肉注射在脾脏中产生的T细胞频率更高,但口服+肌肉注射/舌下免疫的动物血浆IgG亲和力更高,并且更常表现出黏膜IgA反应。

结论

这些结果表明,通过口服和肌肉注射途径联合递送HIV DNA/MVA疫苗可能是产生全身和黏膜抗体的最佳方式。

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