National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli County, Taiwan.
Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan.
Emerg Microbes Infect. 2023 Dec;12(2):2249130. doi: 10.1080/22221751.2023.2249130.
Antigen sparing is an important strategy for pandemic vaccine development because of the limitation of worldwide vaccine production during disease outbreaks. However, several clinical studies have demonstrated that the current aluminum (Alum)-adjuvanted influenza vaccines fail to sufficiently enhance immune responses to meet licensing criteria. Here, we used pandemic H7N9 as a model virus to demonstrate that a 10-fold lower amount of vaccine antigen combined with Alum and TLR9 agonist can provide stronger protective effects than using Alum as the sole adjuvant. We found that the Alum/CpG 1018 combination adjuvant could induce more robust virus-specific humoral immune responses, including higher total IgG production, hemagglutination-inhibiting antibody activity, and neutralizing antibody titres, than the Alum-adjuvanted formulation. Moreover, this combination adjuvant shifted the immune response toward a Th1-biased immune response. Importantly, the Alum/CpG 1018-formulated vaccine could confer better protective immunity against H7N9 challenge than that adjuvanted with Alum alone. Notably, the addition of CpG 1018 to the Alum-adjuvanted H7N9 whole-virion vaccine exhibited an antigen-sparing effect without compromising vaccine efficacy. These findings have significant implications for improving Alum-adjuvanted influenza vaccines using the approved adjuvant CpG 1018 for pandemic preparedness.
抗原节约是大流行疫苗开发的重要策略，因为在疾病爆发期间，全球疫苗生产受到限制。然而，几项临床研究表明，目前的铝（Alum）佐剂流感疫苗未能充分增强免疫反应，以达到许可标准。在这里，我们使用大流行 H7N9 作为模型病毒来证明，与仅使用 Alum 作为佐剂相比，将疫苗抗原的量减少 10 倍，与 Alum 和 TLR9 激动剂结合使用可以提供更强的保护作用。我们发现 Alum/CpG 1018 联合佐剂可以诱导更强大的病毒特异性体液免疫反应，包括更高的总 IgG 产生、血凝抑制抗体活性和中和抗体滴度，比 Alum 佐剂配方更有效。此外，这种联合佐剂将免疫反应转向 Th1 偏向的免疫反应。重要的是，与单独用 Alum 佐剂的疫苗相比， Alum/CpG 1018 配方的疫苗可以更好地提供针对 H7N9 攻击的保护免疫。值得注意的是，CpG 1018 的添加到 Alum 佐剂的 H7N9 全病毒疫苗中表现出抗原节约效应，而不影响疫苗效力。这些发现对于使用已批准的佐剂 CpG 1018 改进 Alum 佐剂流感疫苗以应对大流行具有重要意义。
