Laboratorio de Desenvolvimento de Vacinas, Instituto Butantan, Sao Paulo, Brazil.
Programa de Pos-Graduacao Interunidades em Biotecnologia, Instituto de Ciencias Biomedicas, Universidade de Sao Paulo (USP), Sao Paulo, Brazil.
Front Immunol. 2020 Oct 30;11:568694. doi: 10.3389/fimmu.2020.568694. eCollection 2020.
Leptospirosis is a zoonotic disease of worldwide distribution, affecting both humans and animals. The development of an effective vaccine against leptospirosis has long been pursued but without success. Humans are contaminated after direct contact with the urine of infected animals or indirectly by contaminated water or soil. The vaccines available consist of inactivated whole-bacterial cells, and the active immunoprotective antigen is the lipopolysaccharide moiety, which is also the basis for serovar classification. However, these vaccines are short-lasting, and protection is only against serovars contained in the preparation. The search for prevalent antigens, present in pathogenic species of , represents the most cost-effective strategy for prevention of leptospirosis. Thus, the identification of these antigens is a priority. In this study, we examined the immunoprotective effect of eight leptospiral recombinant proteins using hamster as the challenge model. Animals received subcutaneously two doses of vaccine containing 50 g of each recombinant protein adsorbed on alum adjuvant. Two weeks after the booster, animals were challenged with virulent leptospires and monitored for 21 days. All proteins were able to induce a specific immune response, although significant protective effects on survival rate were observed only for the proteins Lsa14, rLIC13259, and rLIC11711. Of these, only rLIC13259 and rLIC11711 were found to be highly prospective in promoting renal clearance. The sterilizing potential of both proteins will be further investigated to elucidate the immunoprotective mechanisms involved in leptospirosis control. These are the first proteins involved with human complement components with the capacity to protect against virulent challenge and to eliminate the bacteria from the host.
钩端螺旋体病是一种分布广泛的人畜共患疾病，影响人类和动物。长期以来，人们一直致力于开发针对钩端螺旋体病的有效疫苗，但均未成功。人类在直接接触受感染动物的尿液或间接接触受污染的水或土壤后会被感染。现有的疫苗由灭活的全细菌细胞组成，主动免疫保护抗原是脂多糖部分，这也是血清型分类的基础。然而，这些疫苗的持续时间较短，并且只能预防制剂中包含的血清型。寻找流行抗原，存在于致病性钩端螺旋体物种中，代表了预防钩端螺旋体病的最具成本效益的策略。因此，鉴定这些抗原是当务之急。在这项研究中，我们使用仓鼠作为挑战模型，检查了八种钩端螺旋体重组蛋白的免疫保护效果。动物接受两次皮下注射疫苗，每剂疫苗含有 50µg 吸附在明矾佐剂上的每种重组蛋白。加强针两周后，用有毒力的钩端螺旋体对动物进行攻击，并监测 21 天。所有蛋白均能诱导特异性免疫反应，尽管仅观察到蛋白 Lsa14、rLIC13259 和 rLIC11711 对生存率有显著的保护作用。在这些蛋白中，只有 rLIC13259 和 rLIC11711 被发现具有高度促进肾脏清除的潜力。这两种蛋白的杀菌潜力将进一步研究，以阐明控制钩端螺旋体病涉及的免疫保护机制。这些是第一批与人类补体成分结合具有保护作用的蛋白，能抵抗强毒攻击并从宿主中消除细菌。
