ORIGINAL RESEARCH article
Front. Immunol.
Sec. Vaccines and Molecular Therapeutics
This article is part of the Research TopicNew Insights in Nucleic Acid Approaches for Vaccine and Biologic DeliveryView all 15 articles
Synthetic DNA co-immunization with vaccine-aligned common consensus nucleoprotein and hemagglutinin protects mice against lethal influenza infection with a single immunization
Provisionally accepted
Ebony Gary
Abigail Rose Trachtman
Dan Wang
Suman Bharti
Ying Ye
Nicholas J TursiMartina TomirottiJillian EisenhauerJacqueline D. ChuDavid Custodio Zegarra
Casey HojeckiMicki ZhengJayamanna Wickramasinghe
David Weiner
Ami Patel*- Wistar Institute, Philadelphia, United States
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There is an urgent need for influenza vaccine strategies that enhance protection against influenza virus drift and across different subtypes. The conserved viral nucleoprotein (NP) is the most abundant viral protein during replication, and a target for broadly protective cellular immune responses. Guided by annual WHO-recommended seasonal vaccine strains, we engineered synthetic DNA vaccine candidates encoding vaccine-aligned common consensus (VACC) immunogens designed to represent the immune diversity of seasonal H1N1 and H3N2 virus NP proteins (pVACC-NPH1; pVACC-NPH3). Both pVACC-NPH1 and pVACC-NPH3 DNA vaccines induced robust cellular immune responses in mice, including the induction of durable responses. Immunization with a single dose of either DNA vaccine 14 days prior to lethal A/California/2009 H1N1 virus challenge provided protection against mortality. Single dose co-administration of pVACC-NPH3 with an HA-expressing DNA vaccine (pHAH1) and plasmid-encoded adjuvant pIL-12 afforded improved protection against morbidity and mortality in a high-dose challenge model. These data highlight the potential of heterologous cellular immunity induced by engineered NP immunogens to complement HA-based approaches to significantly improve challenge outcomes.
Keywords: Influenza A virus, nucleoprotein, hemagglutinin, Synthetic DNA, Multivalent vaccine
Received: 20 May 2025; Accepted: 29 Oct 2025.
Copyright: © 2025 Gary, Trachtman, Wang, Bharti, Ye, Tursi, Tomirotti, Eisenhauer, Chu, Custodio Zegarra, Hojecki, Zheng, Wickramasinghe, Weiner and Patel. 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: Ami Patel, apatel@wistar.org
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