Kim Jiho, Davis Jenn, Berube Bryan, Duthie Malcolm, Gray Sean A, Carter Darrick
PAI Life Sciences Inc., Seattle, WA 98102, USA.
HDT Bio Corp., Seattle, WA 98109, USA.
Vaccines (Basel). 2025 Jul 28;13(8):797. doi: 10.3390/vaccines13080797.
: mRNA vaccines introduced during the COVID-19 pandemic were a significant step forward in the rapid development and deployment of vaccines in a global pandemic context. These vaccines showed good protective efficacy, but-due to limited breadth of the immune response-they required frequent boosters with manufactured spike sequences that often lagged behind the circulating strains. In order to enhance the breadth, durability, and magnitude of immune responses, we studied the effect of combining priming with an RNA vaccine technology with boosting with protein/adjuvant using a TLR4-agonist based adjuvant. : Specifically, four proprietary adjuvants (EmT4, LiT4Q, MiT4, and AlT4) were investigated in combination with multiple modes of SARS-CoV-2 vaccination (protein, peptide, RNA) for their effectiveness in boosting antibody responses to SARS-CoV-2 spike protein in murine models. : Results showed significant improvement in immune response strength and breadth-especially against more distant SARS-CoV-2 variants such as Omicron-when adjuvants were used in combination with boosters following an RNA vaccine prime. : The use of novel TLR4 adjuvants in combination with protein or RNA vaccinations presents a promising strategy for improving the efficacy of vaccines in the event of future pandemics, by leveraging rapid response using an RNA vaccine prime and following up with protein/adjuvant-based vaccines to enhance the breadth of immunity.
在新冠疫情期间推出的信使核糖核酸（mRNA）疫苗，是在全球疫情背景下快速研发和部署疫苗方面向前迈出的重要一步。这些疫苗显示出良好的保护效力，但由于免疫反应的广度有限，它们需要频繁接种含有制造的刺突序列的加强针，而这些序列往往落后于流行毒株。为了增强免疫反应的广度、持久性和强度，我们研究了将基于RNA疫苗技术的初次免疫与使用基于Toll样受体4（TLR4）激动剂的佐剂进行蛋白/佐剂加强免疫相结合的效果。具体而言，研究了四种专利佐剂（EmT4、LiT4Q、MiT4和AlT4）与多种严重急性呼吸综合征冠状病毒2（SARS-CoV-2）疫苗接种模式（蛋白、肽、RNA）联合使用时，在小鼠模型中增强针对SARS-CoV-2刺突蛋白抗体反应的有效性。结果显示，当佐剂与RNA疫苗初次免疫后的加强针联合使用时，免疫反应的强度和广度有显著改善，尤其是针对如奥密克戎这样较远的SARS-CoV-2变体。通过利用RNA疫苗初次免疫的快速反应，并随后使用基于蛋白/佐剂的疫苗来增强免疫广度，将新型TLR4佐剂与蛋白或RNA疫苗接种联合使用，为在未来疫情中提高疫苗效力提供了一种有前景的策略。
