Vaccines · Published 2026-08-02 · DOI 10.3390/vaccines14080671
Hongzhe Lin, Mingyue Chen, Rong Xiang, Yating Kang, Yiwei Zhong, Duan Ma, Bin Wang
Background: DNA vaccines are widely used due to their low production cost, ease of large-scale manufacturing, and rapid responsiveness to emerging epidemics. However, their relatively modest immunogenicity in larger species often requires potent adjuvants to elicit robust protective responses. GM-CSF and Flt3L are two cytokine adjuvants targeting dendritic cells (DCs). Although their combination has been reported to augment immune responses, the mechanism underlying the complementary effects of a genetically fused GM-CSF-Flt3L adjuvant plasmid remains incompletely understood. Methods: We constructed a GM-CSF-Flt3L fusion adjuvant plasmid and compared it with single-adjuvant plasmids for their effects on innate, humoral, and cellular immunity, as well as protective efficacy against lethal homologous virus challenge. Results: Compared with single-adjuvant plasmids, GM-CSF-Flt3L synergistically promoted the maturation of bone marrow-derived dendritic cells (BMDCs) and activated draining lymph node DCs, differentially expanded DC subsets, and enhanced the recruitment of migratory DCs. This adjuvant significantly elevated hemagglutinin (HA)-specific serum IgG titers, hemagglutination inhibition (HI) titers, and the responses of T follicular helper (TFH) cells and germinal center B (GCB) cells, while also enhancing the capacity of HA-specific CD4<sup>+</sup> and CD8<sup>+</sup> T cells to secrete IFN-γ and TNF-α. Following lethal homologous virus challenge, the GM-CSF-Flt3L group exhibited markedly reduced lung viral loads and no significant pathological damage in lung tissues. Conclusions: These findings demonstrate that the GM-CSF-Flt3L fusion adjuvant complementarily enhances humoral and cellular immune responses induced by the influenza DNA vaccine and improves protective efficacy, highlighting its potential as an effective DNA vaccine adjuvant.
Abstract from DOAJ. Public domain (CC0 1.0).
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Lin, H., Chen, M., Xiang, R., et al. (2026). A GM-CSF-Flt3L Fused Adjuvant Enhances Immune Responses and Protective Efficacy of Influenza DNA Vaccine in Mice. Vaccines. https://doi.org/10.3390/vaccines14080671