Authors
Helen Horton, Robert F Cunliffe, Sungwon Kim, Madina Wane, Lisa J Caproni, John S Tregoning, Alexander M de Bruin
Published in
Molecular therapy : the journal of the American Society of Gene Therapy. Sep 22, 2026. Epub Sep 22, 2026.
Abstract
Nucleic acid vaccines offer rapid and flexible platforms for addressing infectious diseases but achieving durable and balanced immunity remains a challenge. We evaluated a closed linear synthetic Doggybone™ DNA vaccine (dbDNA™) encoding influenza A/California/07/2009 hemagglutinin across delivery platforms and preclinical models. In minipigs, dbDNA elicited comparable or stronger antibody and T cell responses than plasmid DNA when delivered by needle-free intradermal injection or intramuscular electroporation. Direct comparison of LNP-formulated dbDNA with nucleoside-modified mRNA vaccines revealed platform- and species-specific immune profiles. In mice, mRNA induced higher antibody titers, whereas T cell responses were broadly comparable, though dose response effects differed. In non-human primates (NHP), both vaccines (delivered as a 20μg dose) elicited robust antibody titers with different kinetics: mRNA responses declined shortly after peak, whereas dbDNA titers persisted. Additionally, dbDNA induced a higher proportion of functional antibodies and enhanced CD4+ and CD8+ T cell responses, with an immunostimulatory cytokine profile. These results demonstrate that LNP-formulated dbDNA elicits durable humoral and cellular immunity, at low dose, in NHPs, with distinct kinetics and functional profiles compared to mRNA.
PMID:
42768752
Bibliographic data and abstract were imported from PubMed on 22 Sep 2026.
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