Instituto de Investigación Marqués de Valdecilla (IDIVAL), Santander, Spain.
Grupo de Oncología y Nanovacunas, Santander, Spain.
Front Immunol. 2021 Apr 19;12:632304. doi: 10.3389/fimmu.2021.632304. eCollection 2021.
Cross-reactive vaccines recognize common molecular patterns in pathogens and are able to confer broad spectrum protection against different infections. Antigens common to pathogenic bacteria that induce broad immune responses, such as the glyceraldehyde-3-phosphate dehydrogenase (GAPDH) of the genera , or , whose sequences present more than 95% homology at the N-terminal GAPDH peptide, are putative candidates for universal vaccines. Here, we explore vaccine formulations based on dendritic cells (DC) loaded with two molecular forms of GAPDH (LM-GAPDH), such as mRNA carriers or recombinant proteins, and compare them with the same molecular forms of three other antigens used in experimental vaccines, listeriolysin O of , Ag85A of , and pneumolysin of . DC loaded with LM-GAPDH recombinant proteins proved to be the safest and most immunogenic vaccine vectors, followed by mRNA encoding LM-GAPDH conjugated to lipid carriers. In addition, macrophages lacked sufficient safety as vaccines for all LM-GAPDH molecular forms. The ability of DC loaded with LM-GAPDH recombinant proteins to induce non-specific DC activation explains their adjuvant potency and their capacity to trigger strong CD4 and CD8 T cell responses explains their high immunogenicity. Moreover, their capacity to confer protection in vaccinated mice against challenges with , or validated their efficiency as cross-reactive vaccines. Cross-protection appears to involve the induction of high percentages of GAPDH specific CD4 and CD8 T cells stained for intracellular IFN-γ, and significant levels of peptide-specific antibodies in vaccinated mice. We concluded that DC vaccines loaded with GAPDH recombinant proteins are cross-reactive vaccines that seem to be valuable tools in adult vaccination against , and taxonomic groups.
交叉反应疫苗识别病原体中的共同分子模式，能够提供针对不同感染的广谱保护。诱导广泛免疫反应的致病性细菌的共同抗原，如属的甘油醛-3-磷酸脱氢酶（GAPDH）或属的甘油醛-3-磷酸脱氢酶，其 N 端 GAPDH 肽的序列同源性超过 95%，是通用疫苗的候选者。在这里，我们探索了基于负载两种分子形式的树突状细胞（DC）的疫苗配方GAPDH（LM-GAPDH），例如 mRNA 载体或重组蛋白，并将它们与三种其他实验疫苗中使用的相同分子形式进行了比较，即李斯特菌的溶血素 O、结核分枝杆菌的 Ag85A 和肺炎链球菌的肺炎球菌溶血素。负载 LM-GAPDH 重组蛋白的 DC 被证明是最安全和最具免疫原性的疫苗载体，其次是与脂质载体偶联的编码 LM-GAPDH 的 mRNA。此外，对于所有 LM-GAPDH 分子形式，巨噬细胞作为疫苗缺乏足够的安全性。负载 LM-GAPDH 重组蛋白的 DC 诱导非特异性 DC 激活的能力解释了它们的佐剂效力，以及它们触发强烈 CD4 和 CD8 T 细胞反应的能力解释了它们的高免疫原性。此外，它们在接种小鼠中抵御挑战的能力，或验证了它们作为交叉反应疫苗的效率。交叉保护似乎涉及诱导高水平的 GAPDH 特异性 CD4 和 CD8 T 细胞，这些细胞对细胞内 IFN-γ进行染色，并在接种小鼠中产生显著水平的肽特异性抗体。我们得出结论，负载 GAPDH 重组蛋白的 DC 疫苗是交叉反应疫苗，它们似乎是针对成人接种、和分类群的有价值的工具。
