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MPLA和AddaVax佐剂未能增强肌肉注射LaAg疫苗对实验性皮肤利什曼病的保护作用。

MPLA and AddaVax Adjuvants Fail to Promote Intramuscular LaAg Vaccine Protectiveness against Experimental Cutaneous Leishmaniasis.

作者信息

Oliveira-Maciel Diogo, Dos-Santos Júlio Souza, Oliveira-Silva Gabriel, Mello Mirian França de, da Fonseca-Martins Alessandra Marcia, Carneiro Monique Pacheco Duarte, Ramos Tadeu Diniz, Firmino-Cruz Luan, Gomes Daniel Claudio Oliveira, Rossi-Bergmann Bartira, de Matos Guedes Herbert Leonel

机构信息

Laboratório de Imunofarmacologia, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, Brazil.

Laboratório Interdisciplinar de Pesquisas Médicas, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro 21040-360, Brazil.

出版信息

Microorganisms. 2021 Jun 11;9(6):1272. doi: 10.3390/microorganisms9061272.

Abstract

There is so far no vaccine approved for human leishmaniasis, mainly because of the lack of appropriate adjuvants. This study aimed to evaluate in mice the capacity of a mixture of monophosphoryl lipid A (MPLA) and AddaVax adjuvants in enhancing the efficacy of a Leishvacin-like vaccine comprised of whole antigens (LaAg). For that, mice were immunized with LaAg plus MPLA/AddaVax by the intramuscular route (i.m.) prior to challenge with 2 × 10 and 2 × 10 living parasites. Immunization with LaAg alone reduced the lesion growth of the 2 × 10-challenged mice only in the peak of infection, but that was not accompanied by reduced parasite load, and thus not considered protective. Mice given a 2 × 10 -challenge were not protected by LaAg. The association of LaAg with MPLA/AddaVax was able to enhance the cutaneous hypersensitivity response compared with LaAg alone. Despite this, there was no difference in proliferative cell response to antigen ex vivo. Moreover, regardless of the parasite challenge, association of LaAg with MPL/AddaVax did not significantly enhance protection in comparison with LaAg alone. This work demonstrated that MPL/AddaVax is not effective in improving the efficacy of i.m. LaAg vaccine against cutaneous leishmaniasis.

摘要

到目前为止,还没有被批准用于人类利什曼病的疫苗,主要原因是缺乏合适的佐剂。本研究旨在评估单磷酰脂质A(MPLA)和AddaVax佐剂的混合物在增强由全抗原(LaAg)组成的类利什曼原虫疫苗效力方面对小鼠的作用。为此,在用2×10⁶和2×10⁷活寄生虫攻击之前,通过肌肉注射途径(i.m.)用LaAg加MPLA/AddaVax对小鼠进行免疫。单独用LaAg免疫仅在感染高峰期减少了2×10⁶攻击小鼠的病变生长,但这并未伴随着寄生虫载量的减少,因此不被认为具有保护性。接受2×10⁷攻击的小鼠未受到LaAg的保护。与单独使用LaAg相比,LaAg与MPLA/AddaVax联合使用能够增强皮肤超敏反应。尽管如此,体外对抗原的增殖细胞反应没有差异。此外,无论寄生虫攻击情况如何,与单独使用LaAg相比,LaAg与MPL/AddaVax联合使用并没有显著增强保护作用。这项工作表明,MPL/AddaVax在提高肌肉注射LaAg疫苗抗皮肤利什曼病的效力方面无效。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58bb/8230739/fcbab1075ca8/microorganisms-09-01272-g001.jpg

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