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多价 DNA 疫苗作为应对多种并发传染病的策略：蚊媒和出血热病毒。

Multivalent DNA Vaccines as A Strategy to Combat Multiple Concurrent Epidemics: Mosquito-Borne and Hemorrhagic Fever Viruses.

机构信息

Inovio Pharmaceuticals Inc., Plymouth Meeting, PA 19462, USA.

United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, USA.

出版信息

Viruses. 2021 Feb 27;13(3):382. doi: 10.3390/v13030382.

DOI:10.3390/v13030382
PMID:33673603
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7997291/
Abstract

The emergence of multiple concurrent infectious diseases localized in the world creates a complex burden on global public health systems. Outbreaks of Ebola, Lassa, and Marburg viruses in overlapping regions of central and West Africa and the co-circulation of Zika, Dengue, and Chikungunya viruses in areas with A. aegypti mosquitos highlight the need for a rapidly deployable, safe, and versatile vaccine platform readily available to respond. The DNA vaccine platform stands out as such an application. Here, we present proof-of-concept studies from mice, guinea pigs, and nonhuman primates for two multivalent DNA vaccines delivered using in vivo electroporation (EP) targeting mosquito-borne (MMBV) and hemorrhagic fever (MHFV) viruses. Immunization with MMBV or MHFV vaccines via intradermal EP delivery generated robust cellular and humoral immune responses against all target viral antigens in all species. MMBV vaccine generated antigen-specific binding antibodies and IFNγ-secreting lymphocytes detected in NHPs up to six months post final immunization, suggesting induction of long-term immune memory. Serum from MHFV vaccinated NHPs demonstrated neutralizing activity in Ebola, Lassa, and Marburg pseudovirus assays indicating the potential to offer protection. Together, these data strongly support and demonstrate the versatility of DNA vaccines as a multivalent vaccine development platform for emerging infectious diseases.

摘要

多种同时发生的传染病在全球局部地区出现，给全球公共卫生系统带来了复杂的负担。埃博拉、拉萨热和马尔堡病毒在中非和西非重叠地区的爆发，以及寨卡、登革热和基孔肯雅热病毒在携带 A. aegypti 蚊子的地区的共同传播，突出表明需要一种快速可部署、安全且多功能的疫苗平台，以便及时应对。DNA 疫苗平台就是这样一种应用。在这里，我们展示了使用体内电穿孔（EP）针对蚊媒（MMBV）和出血热（MHFV）病毒靶向的两种多价 DNA 疫苗在小鼠、豚鼠和非人类灵长类动物中进行的概念验证研究。通过皮内 EP 递送对 MMBV 或 MHFV 疫苗进行免疫接种，在所有物种中均针对所有靶病毒抗原产生了强大的细胞和体液免疫应答。MMBV 疫苗在最后一次免疫接种后六个月内可在 NHPs 中产生针对特定抗原的结合抗体和 IFNγ 分泌淋巴细胞，表明诱导了长期免疫记忆。来自 MHFV 疫苗接种的 NHPs 的血清在埃博拉、拉萨热和马尔堡假病毒测定中显示出中和活性，表明有潜力提供保护。总之，这些数据有力地支持并证明了 DNA 疫苗作为新兴传染病多价疫苗开发平台的多功能性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f95/7997291/fcad56669ca9/viruses-13-00382-g007.jpg
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