Department of Microbiology & Immunology, Tulane University School of Medicine, New Orleans, LA, USA.
PATH, Seattle, WA, USA.
Vaccine. 2023 Feb 24;41(9):1589-1601. doi: 10.1016/j.vaccine.2023.01.033. Epub 2023 Jan 31.
A key aspect to vaccine efficacy is formulation stability. Biochemical evaluations provide information on optimal compositions or thermal stability but are routinely validated by ex vivo analysis and not efficacy in animal models. Here we assessed formulations identified to improve or reduce stability of the mucosal adjuvant dmLT being investigated in polio and enterotoxigenic E. coli (ETEC) clinical vaccines. We observed biochemical changes to dmLT protein with formulation or thermal stress, including aggregation or subunit dissociation or alternatively resistance against these changes with specific buffer compositions. However, upon injection or mucosal vaccination with ETEC fimbriae adhesin proteins or inactivated polio virus, experimental findings indicated immunization route and co-administered antigen impacted vaccine immunogenicity more so than dmLT formulation stability (or instability). These results indicate the importance of both biochemical and vaccine-derived immunity assessment in formulation optimization. In addition, these studies have implications for use of dmLT in clinical settings and for delivery in resource poor settings.
疫苗效力的一个关键方面是配方稳定性。生化评估提供了有关最佳成分或热稳定性的信息，但通常通过离体分析而不是动物模型中的功效来验证。在这里，我们评估了为改善或降低粘膜佐剂 dmLT 的稳定性而确定的配方，该佐剂正在用于脊髓灰质炎和肠毒素性大肠杆菌 (ETEC) 临床疫苗的研究中。我们观察到配方或热应激对 dmLT 蛋白的生化变化，包括聚集或亚基解离，或者用特定的缓冲液成分抵抗这些变化。然而，在用 ETEC 菌毛粘附蛋白或灭活脊髓灰质炎病毒进行注射或粘膜接种后，实验结果表明免疫途径和同时给予的抗原对疫苗免疫原性的影响大于 dmLT 配方的稳定性（或不稳定性）。这些结果表明，在配方优化中，生化和疫苗衍生免疫评估都很重要。此外，这些研究对 dmLT 在临床环境中的使用以及在资源匮乏环境中的输送具有重要意义。
