Gupta Sneh Lata, Meyer Alexander R, Kay-Tsumagari Erika, Cheng Wei
Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI, United States.
Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, MI, United States.
Front Immunol. 2025 Aug 19;16:1639371. doi: 10.3389/fimmu.2025.1639371. eCollection 2025.
The durability of vaccine-induced protection is a critical parameter in assessing the overall quality and long-term effectiveness of a vaccine. While the lifelong immunity conferred by certain vaccines is well recognized, the molecular components that underpin such long-lasting protection remain poorly understood. This knowledge gap is further complicated by the frequent inclusion of adjuvant formulations in licensed vaccines, the mechanisms of which are often multifaceted and not fully elucidated. In this review, drawing upon the portfolio of FDA-approved antiviral vaccines and incorporating insights from our own published studies in rodents, we propose that a virus-like structure - devoid of any engineered adjuvants - is all that is needed for a long-lasting IgG response in both mice and humans. This structure comprises two essential features: (1) the oriented display of viral surface protein antigens on a virus-sized scaffold, and (2) internal nucleic acids with native phosphodiester backbones. In fact, several inactivated virus vaccines that conform to this architecture have demonstrated effective and durable protection in human populations without the need for engineered adjuvants. Clarifying these structural and molecular determinants of viral immunogenicity may reduce the empirical nature of vaccine development, enable the rational design of next-generation self-adjuvanting antiviral vaccines, and inspire novel applications in noncommunicable diseases.
疫苗诱导的保护作用的持久性是评估疫苗整体质量和长期有效性的关键参数。虽然某些疫苗赋予的终身免疫力已得到广泛认可，但支撑这种长期保护作用的分子成分仍知之甚少。由于已获许可的疫苗中经常包含佐剂配方，而其作用机制往往是多方面的且尚未完全阐明，这一知识空白进一步复杂化。在本综述中，借鉴美国食品药品监督管理局（FDA）批准的抗病毒疫苗组合，并结合我们自己在啮齿动物身上发表的研究见解，我们提出，一种不含任何工程佐剂的病毒样结构是在小鼠和人类中引发持久IgG反应所必需的全部要素。这种结构包含两个基本特征：（1）病毒表面蛋白抗原在病毒大小的支架上定向展示，以及（2）具有天然磷酸二酯主链的内部核酸。事实上，几种符合这种结构的灭活病毒疫苗已在人群中证明了有效且持久的保护作用，而无需工程佐剂。阐明病毒免疫原性的这些结构和分子决定因素可能会减少疫苗开发的经验性，实现下一代自佐剂抗病毒疫苗的合理设计，并激发在非传染性疾病中的新应用。
