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一种泛真菌疫苗在曲霉病、念珠菌病和肺孢子菌病临床前模型中的免疫原性和保护效力。

Immunogenicity and protective efficacy of a pan-fungal vaccine in preclinical models of aspergillosis, candidiasis, and pneumocystosis.

作者信息

Rayens Emily, Rabacal Whitney, Willems Hubertine M E, Kirton Gabrielle M, Barber James P, Mousa Jarrod J, Celia-Sanchez Brandi N, Momany Michelle, Norris Karen A

机构信息

Center for Vaccines and Immunology, University of Georgia, Athens, GA 30602, USA.

Department of Infectious Diseases, University of Georgia, Athens, GA 30602, USA.

出版信息

PNAS Nexus. 2022 Nov 4;1(5):pgac248. doi: 10.1093/pnasnexus/pgac248. eCollection 2022 Nov.

Abstract

Invasive fungal infections cause over 1.5 million deaths worldwide. Despite increases in fungal infections as well as the numbers of individuals at risk, there are no clinically approved fungal vaccines. We produced a "pan-fungal" peptide, NXT-2, based on a previously identified vaccine candidate and homologous sequences from , and . We evaluated the immunogenicity and protective capacity of NXT-2 in murine and nonhuman primate models of invasive aspergillosis, systemic candidiasis, and pneumocystosis. NXT-2 was highly immunogenic and immunized animals had decreased mortality and morbidity compared to nonvaccinated animals following induction of immunosuppression and challenge with , or . Data in multiple animal models support the concept that immunization with a pan-fungal vaccine prior to immunosuppression induces broad, cross-protective antifungal immunity in at-risk individuals.

摘要

侵袭性真菌感染在全球范围内导致超过150万人死亡。尽管真菌感染以及高危个体数量有所增加,但目前尚无临床批准的真菌疫苗。我们基于先前鉴定的候选疫苗以及来自[具体来源1]、[具体来源2]和[具体来源3]的同源序列,制备了一种“泛真菌”肽NXT-2。我们在侵袭性曲霉病、系统性念珠菌病和肺孢子菌病的小鼠和非人灵长类动物模型中评估了NXT-2的免疫原性和保护能力。NXT-2具有高度免疫原性,与未接种疫苗的动物相比,免疫动物在免疫抑制诱导和用[具体病原体1]、[具体病原体2]或[具体病原体3]攻击后,死亡率和发病率有所降低。多个动物模型的数据支持这样的概念,即在免疫抑制之前用泛真菌疫苗进行免疫可在高危个体中诱导广泛的、交叉保护性的抗真菌免疫。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0169/9802316/22b7718778c4/pgac248fig1.jpg

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