Immunization against full-length protein and peptides from the Lutzomyia longipalpis sand fly salivary component maxadilan protects against Leishmania major infection in a murine model.
Immunization against full-length protein and peptides from the Lutzomyia longipalpis sand fly salivary component maxadilan protects against Leishmania major infection in a murine model.
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DOI：
10.1016/j.vaccine.2017.10.039
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发表时间：
2017-12-04
期刊：
影响因子：
5.5
通讯作者：
Dow SW
中科院分区：
文献类型：
--
作者：
Wheat WH;Arthun EN;Spencer JS;Regan DP;Titus RG;Dow SW
针对maxadilan（MAX）的疫苗接种保护小鼠免受加重的利什曼原虫感染。针对MAX的疫苗接种增加了引流淋巴结中产生IFN-γ的细胞的数量。肽MAX-CLDC疫苗提高了针对MAX介导的免疫调节的宿主免疫力。利什曼病是一种由节肢动物传播的疾病，引起相当大的人类发病率和死亡率。疫苗接种仍然是最现实和实用的手段，以中断不断增长的数量和多样性的白蛉病媒和水库的利什曼原虫。由于利什曼原虫的传播完全由白蛉媒介通过免疫调节唾液物质实现，因此需要未经修饰的宿主免疫应答才能成功的常规疫苗接种可能注定失败，除非免疫调节因子以某种方式被中和。采用阳离子脂质体DNA复合物（CLDC）作为佐剂系统，沿着Lu。长须沙蝇唾液成分maxadilan（MAX）作为抗原（Ag），我们表明小鼠免受MAX诱导的大型利什曼原虫（Lm）感染加重。CLDC佐剂和明矾在病变硬结和降低寄生虫负荷方面相当，然而明矾佐剂在注射部位施加更多炎症。用含有全长MAX或跨越MAX的N-和C-末端区域的肽的MAX-CLDC疫苗接种的BALB/c、C3 H和C57 BL/6小鼠被保护免受与MAX共注射的Lm的足垫攻击。当与未接种疫苗的对照相比时，用含有涵盖MAX的C-末端结构域的前20个N-末端AA的肽或跨越MAX的C-末端结构域的最后15个AA的肽的CLDC免疫的所有小鼠品系在用Lm + MAX攻击后9或18周后表现出降低的寄生虫负荷。MAX-CLDC免疫小鼠的足垫引流淋巴结中IFNγ分泌增加，IL-4分泌减少。C-末端肽（P11）MAX-CLDC免疫动物的抗血清能够识别FL-MAX及其C-末端结构域，并在体外阻断MAX介导的骨髓来源的树突状细胞（BM-DC）重编程。这种靶向白蛉MAX的肽疫苗提高了针对MAX介导的免疫调节的宿主免疫力。
Vaccination against maxadilan (MAX) protect mice from aggravated Leishmania infection. Vaccination against MAX increases the number of IFN-γ-producing cells in draining lymph nodes. The peptide MAX-CLDC vaccine improves host immunity against MAX-mediated immune modulation. Leishmaniasis is an arthropod vectored disease causing considerable human morbidity and mortality. Vaccination remains the most realistic and practical means to interrupt the growing number and diversity of sand fly vectors and reservoirs of Leishmania. Since transmission of Leishmania is achieved exclusively by sand fly vectors via immune-modulating salivary substances, conventional vaccination requiring an unmodified host immune response for success are potentially destined to fail unless immunomodulatory factors are somehow neutralized. Using cationic liposome DNA complexes (CLDC) as an adjuvant system along with Lu. longipalpis sand fly salivary component maxadilan (MAX) as antigen (Ag), we show that mice are protected from the MAX-induced exacerbation of infection with Leishmania major (Lm). The CLDC adjuvant and alum were comparable in terms of lesion induration and decreased parasite burden, however the alum adjuvant imposed more inflammation at the injection site. BALB/c, C3H and C57BL/6 mice vaccinated with MAX-CLDC containing either the full-length MAX or peptides spanning the N- and C-terminal regions of MAX are protected against footpad challenges with Lm co-injected with MAX. When compared to unvaccinated controls, all strains of mice immunized with CLDC containing either peptides encompassing the first 20 N-terminal AA or those spanning the last 15 AA of the C-terminal domain of MAX demonstrated decreased parasite burden after 9 or 18 weeks post challenge with Lm + MAX. MAX-CLDC immunized mice showed increased IFNγ-secreting and decreased IL-4-secreting CD4+ cells in footpad-draining lymph nodes. Antisera from C-terminal peptide (P11) MAX-CLDC-vaccinated animals was capable of recognizing FL-MAX and its C-terminal domain and also blocked MAX-mediated reprogramming of bone marrow-derived dendritic cells (BM-DC) in vitro. This peptide vaccine targeting sand fly MAX, improves host immunity against MAX-mediated immunomodulation.
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DOI：
10.1073/pnas.0802331105
发表时间：
2008-07-22
影响因子：
11.1
作者：
Kimblin, Nicola;Peters, Nathan;Sacks, David
通讯作者：
Sacks, David
影响因子：
4.8
作者：
Moro, O;Wakita, K;Tajima, M
通讯作者：
Tajima, M
影响因子：
17.1
作者：
Oliveira, Fabiano;Rowton, Edgar;Valenzuela, Jesus G.
通讯作者：
Valenzuela, Jesus G.
DOI：
10.4269/ajtmh.2006.75.532
发表时间：
2006-09-01
影响因子：
3.3
作者：
Bishop, Jeanette V.;Mejia, J. Santiago;Titus, Richard G.
通讯作者：
Titus, Richard G.
DOI：
10.1016/s0169-4758(96)40010-2
发表时间：
1997-02-01
期刊：
PARASITOLOGY TODAY
影响因子：
--
作者：
Lima, HC;Bleyenberg, JA;Titus, RG
通讯作者：
Titus, RG