REVIEW article
Front. Immunol.
Sec. Vaccines and Molecular Therapeutics
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1646800
This article is part of the Research TopicNew Insights in Nucleic Acid Approaches for Vaccine and Biologic DeliveryView all 11 articles
Advances in Molecular Adjuvants for Nucleic Acid Vaccines
Provisionally accepted
- Wistar Institute, Philadelphia, United States
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As nucleic acid vaccine technology continues to advance, modern adjuvants are being engineered to quantitatively and qualitatively shape immune responses. Since their development in the early 1990's, nucleic acid approaches have garnered significant attention, and numerous platform technologies have been developed both to improve delivery as well as immunogenicity. These advances were highlighted during the COVID-19 pandemic, with the approval of both mRNA-LNP and DNA vaccines for SARS-CoV-2. Early clinical trials with DNA antigens alone displayed suboptimal immunogenicity, supporting interest in adjuvant molecules. Molecular adjuvants, nucleic acid-encoded cytokines, chemokines, and enzymes, among others, are used to enhance and direct nucleic acid antigen-induced immunity in vivo. Additionally, mRNA-LNP vaccines, and more recently DNA-LNP vaccines, have demonstrated robust immunogenicity with intrinsic adjuvant activity based on the delivery mode. This review summarizes the molecular adjuvant landscape and highlights recent findings in the context of nucleic acid vaccines.
Keywords: Nucleic acid vaccines, adjuvant, gene-encoded adjuvants, Molecular adjuvants, Plasmid-encoded, DNA Vaccines, mRNA vaccines
Received: 13 Jun 2025; Accepted: 04 Aug 2025.
Copyright: © 2025 Hojecki, Tursi, Livingston, Weiner and Gary. 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:
Casey E Hojecki, Wistar Institute, Philadelphia, United States
David Weiner, Wistar Institute, Philadelphia, United States
Ebony Gary, Wistar Institute, Philadelphia, United States
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.