Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Jun 20:59:127231.
doi: 10.1016/j.vaccine.2025.127231. Epub 2025 May 20.

DNA co-delivery of seasonal H1 influenza hemagglutinin nanoparticle vaccines with chemokine adjuvant CTACK induces potent immunogenicity for heterologous protection in vivo

Kevin Liaw  1 , Kylie M Konrath  2 , Abigail R Trachtman  1 , Nicholas J Tursi  2 , Ebony N Gary  1 , Cory Livingston  1 , Kaitlyn Flowers  1 , Jacqueline D Chu  1 , Casey E Hojecki  1 , Niklas Laenger  3 , Madison E McCanna  1 , Colby J Agostino  2 , Neethu Chokkalingam  1 , Kelly Bayruns  1 , Sinja Kriete  1 , Amber Kim  1 , Joyce Park  1 , Cara Monastra  1 , Lucas A Pardo  1 , Sarah Jenison  1 , Jinwei Huang  1 , Kathleen Mulka  4 , Ami Patel  1 , Daniel W Kulp  5 , David B Weiner  6
Affiliations

DNA co-delivery of seasonal H1 influenza hemagglutinin nanoparticle vaccines with chemokine adjuvant CTACK induces potent immunogenicity for heterologous protection in vivo

Kevin Liaw et al. Vaccine. .

Abstract

Current influenza vaccines induce mostly strain-specific immunity necessitating annual reformulation and dosing. Here, we developed an improved seasonal influenza vaccine based on A/H1N1/Wisconsin/588/2019. We designed a DNA-launched self-assembling nanoparticle that displayed seven Wisconsin/588/2019 hemagglutinin (HA) head domains (WI19-7mer). WI19-7mer nanovaccine improved heterologous HAI titers and CD8+ cellular responses in mice than DNA encoded HA trimer (WI19 HA). In human antibody repertoire mice, WI19-7mer induced superior breadth to a diverse panel of H1 HAs compared to WI19 HA immunized animals. Cross-reactive HAI titers were maintained better in mice immunized with WI19-7mer than WI19 HA. The WI19-7mer induced improved antibody binding breadth and provided superior protection in a heterologous challenge compared to challenge-matched HA trimer. Addition of the cytokine adjuvant (CTACK) to WI19-7mer significantly improved breadth, HAI, peripheral responses, and protection in heterologous challenge. These data demonstrate that combining nucleic acid delivery, immune focusing, low valency nanoparticle, and mucosal adjuvant for enhanced vaccine effectiveness has broader applications for other viruses.

Keywords: Influenza; Mucosal adjuvant; Nanoparticle vaccine.

PubMed Disclaimer

Conflict of interest statement

Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: David Weiner and Daniel Kulp reports financial support was provided by National Institutes of Health. Kathleen Mulka reports financial support was provided by Abramson Cancer Center. David Weiner reports a relationship with Inovio Pharmaceuticals Inc. that includes: board membership, consulting or advisory, equity or stocks, and funding grants. Daniel Kulp reports a relationship with Inovio Pharmaceuticals Inc. that includes: funding grants. D.B.W. has received grant funding, participates in industry collaborations, has received speaking honoraria and has received fees for consulting, including serving on scientific review committees. Remunerations received by D.B.W. include direct payments and equity/options. D.B.W. also discloses the following associations with commercial partners: Geneos (consultant/advisory board), AstraZeneca (advisory board, speaker), Inovio (board of directors, consultant), BBI/Sumitomo Dainippon (advisory board), Flagship (consultant), Pfizer (advisory board) and Advaccine (consultant). If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

MeSH terms