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REVIEW article

Front. Immunol.

Sec. Vaccines and Molecular Therapeutics

Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1639371

Molecular ingredients of an immunogen for long-lasting IgG

Provisionally accepted
  • University of Michigan, Ann Arbor, United States

The final, formatted version of the article will be published soon.

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 FDAapproved 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.

Keywords: virus, Vaccine, antibody, IgG, Persistence, durability

Received: 02 Jun 2025; Accepted: 30 Jul 2025.

Copyright: © 2025 Gupta, Meyer, Kay-Tsumagari and Cheng. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Wei Cheng, University of Michigan, Ann Arbor, United States

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