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用环状二腺苷酸（c-di-AMP）佐剂经鼻内递送流感核糖核蛋白（rNP）可诱导强烈的体液免疫和细胞免疫反应，并提供针对病毒攻击的保护作用。

Intranasal delivery of influenza rNP adjuvanted with c-di-AMP induces strong humoral and cellular immune responses and provides protection against virus challenge.

作者信息

Sanchez Maria Victoria, Ebensen Thomas, Schulze Kai, Cargnelutti Diego, Blazejewska Paulina, Scodeller Eduardo A, Guzmán Carlos A

机构信息

Laboratory of Virology, Institute of Experimental Medicine and Biology of Cuyo (IMBECU-CCT, CONICET), Mendoza, Argentina; Department of Vaccinology and Applied Microbiology, Helmholtz Centre for Infection Research, Braunschweig, Germany.

Department of Vaccinology and Applied Microbiology, Helmholtz Centre for Infection Research, Braunschweig, Germany.

出版信息

PLoS One. 2014 Aug 20;9(8):e104824. doi: 10.1371/journal.pone.0104824. eCollection 2014.

DOI:10.1371/journal.pone.0104824
PMID:25140692
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4139298/
Abstract

There is a critical need for new influenza vaccines able to protect against constantly emerging divergent virus strains. This will be sustained by the induction of vigorous cellular responses and humoral immunity capable of acting at the portal of entry of this pathogen. In this study we evaluate the protective efficacy of intranasal vaccination with recombinant influenza nucleoprotein (rNP) co-administrated with bis-(3',5')-cyclic dimeric adenosine monophosphate (c-di-AMP) as adjuvant. Immunization of BALB/c mice with two doses of the formulation stimulates high titers of NP-specific IgG in serum and secretory IgA at mucosal sites. This formulation also promotes a strong Th1 response characterized by high secretion of INF-γ and IL-2. The immune response elicited promotes efficient protection against virus challenge. These results suggest that c-di-AMP is a potent mucosal adjuvant which may significantly contribute towards the development of innovative mucosal vaccines against influenza.

摘要

迫切需要能够抵御不断出现的不同病毒株的新型流感疫苗。这将通过诱导能够在该病原体进入门户起作用的强烈细胞反应和体液免疫来维持。在本研究中，我们评估了鼻内接种重组流感核蛋白（rNP）并与双（3'，5'）-环二聚腺苷单磷酸（c-di-AMP）作为佐剂共同给药的保护效果。用两剂该制剂免疫BALB/c小鼠可刺激血清中高滴度的NP特异性IgG以及粘膜部位的分泌型IgA。该制剂还促进以INF-γ和IL-2高分泌为特征的强烈Th1反应。引发的免疫反应促进了对病毒攻击的有效保护。这些结果表明，c-di-AMP是一种有效的粘膜佐剂，可能对开发针对流感的创新型粘膜疫苗做出重大贡献。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/890d/4139298/4d2b4bbffaff/pone.0104824.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/890d/4139298/481b41419782/pone.0104824.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/890d/4139298/538f011e9bf9/pone.0104824.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/890d/4139298/ef1be5a84e63/pone.0104824.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/890d/4139298/682e17e5c153/pone.0104824.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/890d/4139298/4d2b4bbffaff/pone.0104824.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/890d/4139298/481b41419782/pone.0104824.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/890d/4139298/538f011e9bf9/pone.0104824.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/890d/4139298/ef1be5a84e63/pone.0104824.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/890d/4139298/682e17e5c153/pone.0104824.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/890d/4139298/4d2b4bbffaff/pone.0104824.g005.jpg

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