Abstract
The role of T-cell-mediated immune responses is recognized as pivotal in achieving functional cure in chronic hepatitis B (CHB) patients. We aimed to assess safety and T-cell responses induced by JNJ-6430535 (JNJ-0535); a hepatitis B virus (HBV)-specific therapeutic DNA vaccine administered via electroporation-mediated intramuscular injection. JNJ-0535 comprises 2 plasmids, encoding HBV core and polymerase (pol) proteins, respectively. We describe the safety, tolerability, and immunogenicity results of JNJ-0535 from an open-label, single arm phase 1 study in healthy volunteers (HVs) (64300535HPB1003, NTC04736147) and a randomized, placebo controlled phase 1 study in CHB patients (64300535HPB1001, NTC03463369). HBV-specific T-cell responses were evaluated using enzyme-linked immunospot (ELISpot) and intracellular cytokine staining (ICS). We performed baseline single-cell RNA sequencing (scRNA-seq) to explore immune correlates associated with vaccine response in HVs, and baseline serum proteomics (Olink Explore® 3072) to explore differences in soluble immune markers between responders and non-responders in both HVs and CHB patients. JNJ-0535 was safe and well tolerated in both HVs and CHB patients. Compared to CHB patients, HVs showed a higher proportion of participants with vaccine-induced HBV-specific T-cell responses (92% versus 50%), a greater increase from baseline (24× [interquartile range=40×;9×] versus 4.8× [interquartile range=5×;6×]) and a broader response in terms of number of antigens. Serum proteomics revealed few differential circulating host biomarkers between CHB and HVs, but these could not be linked to differences in immunogenicity. In addition, whole-blood scRNA-seq was performed in HVs to explore differences between participants with a strong vaccine response and those with low or no response. Our research showed a decrease in vaccine-induced responses in CHB patients compared to HVs and may provide preliminary insights into immune-related biomarkers that could influence vaccine immunogenicity but require further confirmation in future larger studies. trial numbers: 64300535HPB1001 (NCT03463369) First posted: 18. April 2018; ULR: https://clinicaltrials.gov/study/NCT03463369?term=JNJ-64300535&rank=2 and 64300535HPB1003 (NCT04736147) First posted: 03. Feb. 2021; URL: https://clinicaltrials.gov/study/NCT04736147?term=JNJ-64300535&rank=1.
Data availability
The data sharing policy of Janssen Pharmaceutical Companies of Johnson & Johnson is available at https://www.janssen.com/clinicaltrials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at http://yoda.yale.edu. The single-cell RNA sequencing dataset generated and analyzed during the current study is available in the Zenodo repository https://zenodo.org/records/17120218. The Proteomics dataset generated and analyzed during the current study is available in the Zenodo repository https://zenodo.org/records/17292246.
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Acknowledgements
We would like to acknowledge all participants in both studies. We would like to acknowledge Luc Geeraert for text editing support. Research was sponsored by Johnson & Johnson Innovative Medicine, Research and Development.
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P.T.F.K. and S.B. ran the clinical study in CHB patients. A.D.C., P.V.R., M.B., B.F., and L.S. designed the studies. B.F., L.S., and A.D.C. performed and analysed the viral and blood peripheral readout data set up, performed, and analysed immunology-related data. N.C.N., C.V., and S.V. performed the single-cell RNA-sequencing experiments. S.V., N.C.N., E.D.T., E.E., and D.D.M. analysed the single-cell RNA-sequencing data. M.C. and E.M. analysed the Olink data. E.D.T. and E.E. ran statistical analysis on the exploratory single-cell RNA-sequencing data. L.S. ran the study's statistical analysis. A.D.C., S.V., N.C.N., and M.B. wrote the manuscript. All authors revised and approved the final manuscript.
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S.B. advisor and speaker for AbbVie, Gilead, Bristol Myers Squibb, and Janssen; P.T.F.K. received grants and/or contracts from Aligos and Vir Biotechnology; received consulting fees from Assembly Bio, Bluejay Therapeutics, GlaxoSmithKline, and Gilead Sciences; received honoraria from GlaxoSmithKline and Gilead Sciences; and served in leadership roles in the British Viral Hepatitis Group. S.V., N.C.N., C.V., E.D.T., E.K., D.D.M., M.C., E.M., L.S., B.F., P.V.R., M.B., A.D.C. authors are or were at the time of study conduct employees of Johnson & Johnson Innovative Medicine, Research and Development, and may be Johnson & Johnson stockholders.
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Verheijden, S., Conceição-Neto, N., Bourgeois, S. et al. Safety, immunogenicity, and baseline immune correlates of vaccine JNJ-0535 in participants with or without CHB. npj Vaccines (2026). https://doi.org/10.1038/s41541-025-01364-x
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DOI: https://doi.org/10.1038/s41541-025-01364-x
