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Peptide-based vaccine successfully induces protective immunity against canine visceral leishmaniasis.
npj Vaccines ( IF 6.9 ) Pub Date : 2019-11-29 , DOI: 10.1038/s41541-019-0144-2 Elodie Petitdidier 1 , Julie Pagniez 1 , Joana Pissarra 1 , Philippe Holzmuller 2, 3 , Gérard Papierok 4 , Philippe Vincendeau 1, 5 , Jean-Loup Lemesre 1 , Rachel Bras-Gonçalves 1
npj Vaccines ( IF 6.9 ) Pub Date : 2019-11-29 , DOI: 10.1038/s41541-019-0144-2 Elodie Petitdidier 1 , Julie Pagniez 1 , Joana Pissarra 1 , Philippe Holzmuller 2, 3 , Gérard Papierok 4 , Philippe Vincendeau 1, 5 , Jean-Loup Lemesre 1 , Rachel Bras-Gonçalves 1
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Dogs are the main reservoir of zoonotic visceral leishmaniasis. Vaccination is a promising approach to help control leishmaniasis and to interrupt transmission of the Leishmania parasite. The promastigote surface antigen (PSA) is a highly immunogenic component of Leishmania excretory/secretory products. A vaccine based on three peptides derived from the carboxy-terminal part of Leishmania amazonensis PSA and conserved among Leishmania species, formulated with QA-21 as adjuvant, was tested on naive Beagle dogs in a preclinical trial. Four months after the full course of vaccination, dogs were experimentally infected with Leishmania infantum promastigotes. Immunization of dogs with peptide-based vaccine conferred immunity against experimental infection with L. infantum. Evidence for macrophage nitric oxide production and anti-leishmanial activity associated with IFN-γ production by lymphocytes was only found in the vaccinated group. An increase in specific IgG2 antibodies was also measured in vaccinated dogs from 2 months after immunization. Additionally, after challenge with L. infantum, the parasite burden was significantly lower in vaccinated dogs than in the control group. These data strongly suggest that this peptide-based vaccine candidate generated cross-protection against zoonotic leishmaniasis by inducing a Th1-type immune response associated with production of specific IgG2 antibodies. This preclinical trial including a peptide-based vaccine against leishmaniasis clearly demonstrates effective protection in a natural host. This approach deserves further investigation to enhance the immunogenicity of the peptides and to consider the possible engineering of a vaccine targeting several Leishmania species.
中文翻译：
基于肽的疫苗成功诱导出针对犬内脏利什曼病的保护性免疫。
狗是人畜共患的内脏利什曼病的主要储存库。接种疫苗是帮助控制利什曼病和中断利什曼原虫寄生虫传播的一种有前途的方法。前鞭毛体表面抗原（PSA）是利什曼原虫排泄/分泌产物的高度免疫原性成分。以QA-21为佐剂配制的基于三种来自亚马逊利什曼原虫PSA羧基末端部分的保守保藏在利什曼原虫物种中的肽的疫苗，已在幼稚Beagle犬上进行了临床前试验。整个疫苗接种过程四个月后，实验性地将狗感染了婴儿利什曼原虫前鞭毛体。用基于肽的疫苗对狗进行免疫可赋予抵抗实验性婴儿乳杆菌感染的免疫力。仅在接种组中发现淋巴细胞产生巨噬细胞一氧化氮和与IFN-γ相关的抗利什曼活性的证据。从免疫后2个月开始，在接种疫苗的狗中还测量了特异性IgG2抗体的增加。另外，用婴儿乳杆菌攻击后，接种疫苗的狗的寄生虫负担明显低于对照组。这些数据强烈表明，该基于肽的疫苗候选物通过诱导与特定IgG2抗体产生相关的Th1型免疫应答，产生了针对人畜共患利什曼病的交叉保护作用。该临床前试验包括针对利什曼病的基于肽的疫苗，清楚地证明了对天然宿主的有效保护。
更新日期：2019-11-29
中文翻译：
基于肽的疫苗成功诱导出针对犬内脏利什曼病的保护性免疫。
狗是人畜共患的内脏利什曼病的主要储存库。接种疫苗是帮助控制利什曼病和中断利什曼原虫寄生虫传播的一种有前途的方法。前鞭毛体表面抗原（PSA）是利什曼原虫排泄/分泌产物的高度免疫原性成分。以QA-21为佐剂配制的基于三种来自亚马逊利什曼原虫PSA羧基末端部分的保守保藏在利什曼原虫物种中的肽的疫苗，已在幼稚Beagle犬上进行了临床前试验。整个疫苗接种过程四个月后，实验性地将狗感染了婴儿利什曼原虫前鞭毛体。用基于肽的疫苗对狗进行免疫可赋予抵抗实验性婴儿乳杆菌感染的免疫力。仅在接种组中发现淋巴细胞产生巨噬细胞一氧化氮和与IFN-γ相关的抗利什曼活性的证据。从免疫后2个月开始，在接种疫苗的狗中还测量了特异性IgG2抗体的增加。另外，用婴儿乳杆菌攻击后，接种疫苗的狗的寄生虫负担明显低于对照组。这些数据强烈表明，该基于肽的疫苗候选物通过诱导与特定IgG2抗体产生相关的Th1型免疫应答，产生了针对人畜共患利什曼病的交叉保护作用。该临床前试验包括针对利什曼病的基于肽的疫苗，清楚地证明了对天然宿主的有效保护。
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