Université Paris-Saclay, Inserm, CEA, Center for Immunology of Viral, Auto-immune, Hematological and Bacterial Diseases (IMVA-HB/IDMIT), 92265 Fontenay-aux-Roses, France.
Viral Evolution and Transmission Unit, Division of Immunology, Transplantation and Infectious Diseases, IRCCS Ospedale San Raffaele, 20132 Milan, Italy.
Cell Rep Med. 2022 Oct 18;3(10):100751. doi: 10.1016/j.xcrm.2022.100751. Epub 2022 Sep 26.
Given the time and resources invested in clinical trials, innovative prediction methods are needed to decrease late-stage failure in vaccine development. We identify combinations of early innate responses that predict neutralizing antibody (nAb) responses induced in HIV-Env SOSIP immunized cynomolgus macaques using various routes of vaccine injection and adjuvants. We analyze blood myeloid cells before and 24 h after each immunization by mass cytometry using a three-step clustering, and we discriminate unique vaccine signatures based on HLA-DR, CD39, CD86, CD11b, CD45, CD64, CD14, CD32, CD11c, CD123, CD4, CD16, and CADM1 surface expression. Various combinations of these markers characterize cell families positively associated with nAb production, whereas CADM1-expressing cells are negatively associated (p < 0.05). Our results demonstrate that monitoring immune signatures during early vaccine development could assist in identifying biomarkers that predict vaccine immunogenicity.
鉴于在临床试验中投入的时间和资源,需要创新的预测方法来降低疫苗开发后期的失败率。我们确定了早期先天反应的组合,这些组合可以预测使用不同疫苗注射途径和佐剂免疫的 HIV-Env SOSIP 恒河猴诱导的中和抗体 (nAb) 反应。我们使用三步聚类通过质谱细胞术分析每次免疫前后的血液髓样细胞,并根据 HLA-DR、CD39、CD86、CD11b、CD45、CD64、CD14、CD32、CD11c、CD123、CD4、CD16 和 CADM1 表面表达来区分独特的疫苗特征。这些标记物的各种组合特征是与 nAb 产生呈正相关的细胞家族,而表达 CADM1 的细胞则与之呈负相关(p<0.05)。我们的研究结果表明,在早期疫苗开发过程中监测免疫特征可能有助于识别预测疫苗免疫原性的生物标志物。