Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, United States; Department of Microbiology, Immunology, Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, United States.
Department of Biology, College of Natural Sciences, Colorado State University, Fort Collins, CO 80523, United States.
Vaccine. 2017 Dec 4;35(48 Pt B):6611-6619. doi: 10.1016/j.vaccine.2017.10.039. Epub 2017 Oct 24.
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.
利什曼病是一种节肢动物传播的疾病，会导致相当大的人类发病率和死亡率。接种疫苗仍然是中断不断增加的沙蝇媒介和利什曼原虫储存库的最现实和实用的方法。由于利什曼原虫的传播完全是通过沙蝇媒介通过免疫调节唾液物质来实现的，因此，除非免疫调节因子被某种方式中和，否则需要宿主未修饰的免疫反应才能成功的传统疫苗接种可能注定要失败。我们使用阳离子脂质体 DNA 复合物 (CLDC) 作为佐剂系统，并用 Lu. longipalpis 沙蝇唾液成分 maxadilan (MAX) 作为抗原 (Ag)，结果表明，小鼠可以免受 MAX 诱导的 Leishmania major (Lm) 感染加重的影响。CLDC 佐剂和明矾在病变硬度和寄生虫负荷减少方面相当，但明矾佐剂在注射部位引起更多炎症。用 MAX-CLDC 接种全长 MAX 或跨越 MAX 的 N-和 C-末端区域的肽的 BALB/c、C3H 和 C57BL/6 小鼠可免受与 MAX 共注射的 Lm 足垫挑战的保护。与未接种疫苗的对照相比，用包含涵盖 MAX 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 AA 的肽的 CLDC 接种的所有小鼠在与 Lm + MAX 挑战后 9 或 18 周后寄生虫负荷降低。MAX-CLDC 免疫的小鼠在足垫引流淋巴结中显示出增加的 IFNγ 分泌和减少的 IL-4 分泌的 CD4 细胞。来自 C-末端肽 (P11) MAX-CLDC 疫苗接种动物的抗血清能够识别 FL-MAX 及其 C-末端结构域，并且还在体外阻断 MAX 介导的骨髓来源的树突状细胞 (BM-DC) 的重编程。这种针对沙蝇 MAX 的肽疫苗可改善宿主对 MAX 介导的免疫调节的免疫力。
