Impact of RNA modification and IL-12 boosts on mRNA-LNP vaccine-elicited CD8+ T cell responses
Development of effective HIV-1 vaccines requires strategies for inducing both CD8+ T cell and neutralizing antibody responses. Nucleoside-modified mRNA-lipid-nanoparticles (LNP) induce more potent antibody responses than unmodified mRNA-LNP vaccines, while unmodified mRNA is typically employed for CD8+ T cell-inducing vaccines. Here, we compared the abilities of differing ratios of unmodified versus modified mRNA expressing a SIV conserved-region CD8+ T cell immunogen co-administered with IL-12-encoding mRNA-LNP during boosting to induce CD8+ T cell and humoral responses in non-human primates, assessing responses in ChAdOx1-primed controls in parallel. Serial priming and boosting with fully-unmodified mRNA elicited higher-magnitude, more CD8-biased T cell responses than fully-modified mRNA, that were durably maintained after the IL-12-encoding mRNA boosts. Inclusion of 30% nucleoside-modified mRNA enhanced antibody titers, suggesting potential benefits to a mixed-composition vaccine.
Authors
- Christopher A. Hunter (ORCID: https://orcid.org/0000-0003-3092-1428)
- Sampa Santra (ORCID: https://orcid.org/0000-0002-8796-1714)
- Michelle A. Lifton (ORCID: https://orcid.org/0000-0003-0279-2198)
- Tomáš Hanke (ORCID: https://orcid.org/0000-0002-6076-9546)
- Persephone Borrow (ORCID: https://orcid.org/0000-0002-3877-9780)
- Bette Korber (ORCID: https://orcid.org/0000-0002-2026-5757)
- Laura L. Sutherland (ORCID: https://orcid.org/0000-0003-4119-3884)
- Benjamin Davis (ORCID: https://orcid.org/0000-0003-4048-7653)
- Francois J. Villinger (ORCID: https://orcid.org/0000-0002-7790-2008)
- Garima Dwivedi (ORCID: https://orcid.org/0000-0002-6101-2481)
- Barton F. Haynes (ORCID: https://orcid.org/0000-0002-7643-9023)
- Benjamin Mildenberg (ORCID: https://orcid.org/0000-0002-0645-6047)
- Han Nhat Tran
- Drew Weissman (ORCID: https://orcid.org/0000-0002-1501-6510)
- Georgeanna Morton (ORCID: https://orcid.org/0000-0002-6675-8004)
- Mohamad‐Gabriel Alameh (ORCID: https://orcid.org/0000-0002-5672-6930)
- Anthony T. Phan (ORCID: https://orcid.org/0000-0003-2935-6070)
- Edward F. Kreider (ORCID: https://orcid.org/0000-0003-2330-8430)
- Robert Parks (ORCID: https://orcid.org/0000-0002-6259-7610)
- Justin Su (ORCID: https://orcid.org/0009-0007-3441-7153)
- Susan Pratiksha
- Whitney Edwards
Institutions
- Beth Israel Deaconess Medical Center (US)
- The University of Texas MD Anderson Cancer Center (US)
- Los Alamos National Laboratory (US)
- Harvard University (US)
- Duke University (US)
- University of Oxford (GB)
- Duke Medical Center (US)
- Jenner Institute (GB)
- University of Louisiana at Lafayette (US)
- University of Pennsylvania (US)
Publication Details
- Journal
- bioRxiv (Cold Spring Harbor Laboratory)
- Published
- 2026-11-01
- DOI
- https://doi.org/10.64898/2026.10.26.761945
- Primary Topic
- HIV Research and Treatment
- Type
- preprint
Funders
- University of Louisiana at Lafayette
- National Institutes of Health
- National Institute of Allergy and Infectious Diseases